Senolytic compositions and uses thereof

Abstract

This invention provides a composition comprising (i) a first agent selected from the group consisting of a BH3 mimetic, an HDAC6 inhibitor, and a TLR-1, -2, and / or -4 inhibitor, and (ii) a second agent selected from the group consisting of a mitochondrial uncoupler, a Bcl-2 inhibitor, a p53 / MDM2 inhibitor, a HSP-90 inhibitor, a PI3K / AKT inhibitor, a BET inhibitor, and a general senolytic. This invention also provides related compositions and formulations, methods, and articles of manufacture.

Description

[0001] Dkt. AgeLess-5PCT SENOLYTIC COMPOSITIONS AND USES THEREOF This application claims the benefit of U.S. Provisional Application No.63 / 696,914, filed September 20, 2024, the contents of which are incorporated herein by reference. Throughout this application, various publications are cited. The disclosure of these publications is hereby incorporated by reference into this application to describe more fully the state of the art to which this invention pertains. Field of the Invention The present invention relates to senolytic compositions and methods for ameliorating one or more aging hallmarks in a subject. Background of the Invention Aging, in the physical sense, is characterized by the accumulation of molecular and cellular damage. This damage leads to a deterioration of physiological function and proper homeostasis, and increases the risk of frailty, infirmity, disability, aging-related diseases, and eventually death. For a long time, one of the main causes of aging was considered to be oxidative damage, as promoted and promulgated by Denham Harman's free radical theory of aging (1). According to this dated theory, antioxidants have the ability to neutralize free radicals, thus slowing the aging process. Yet, research shows that most antioxidants do not slow down aging, and could even shorten lifespan or undo the beneficial effects of exercise (2-6). However, in the last 15 years, a better understanding of the aging process has emerged, leading to an understanding of various mechanisms and causes of aging. These include, for example, epigenetic dysregulation, epitranscriptomic dysregulation, a decline in proteinases (proteotoxicity), mitochondrial dysfunction, genomic damage, telomere shortening and attrition, transcriptomic dysregulation, lysosomal dysfunction and crosslinking contributing to the formation of senescent cells, a decline in stem cell function and numbers, changes of the extracellular milieu (e.g., a change to a pro-inflammatory milieu), and changes in intercellular communication. These changes contribute to the aging phenotype and an increased risk and an occurrence of aging-related diseases like heart disease, neurodegenerative diseases (e.g., Alzheimer's disease or vascular dementia), osteoporosis, osteoarthritis, macular degeneration, kidney dysfunction, and others. Senolytics are drugs that selectively clear senescent cells. Senescent cells accumulate with ageing and at causal sites of chronic disorders. There is interest in using senolytics to ameliorate the many hallmarks of aging. However, there remains an unmet need for superior senolytic formulations able to do so. Summary of the Invention This invention provides a composition comprising (i) a first agent selected from the group consisting of a BH3 mimetic, an HDAC6 inhibitor, and a TLR-1, -2, and / or -4 inhibitor, and (ii) a second agent selected from the group consisting of a mitochondrial uncoupler, a Bcl-2 inhibitor, a p53 / MDM2 inhibitor, a HSP-90 inhibitor, a PI3K / AKT inhibitor, a BET inhibitor, and a general senolytic. This invention also provides a composition comprising (i) the present composition and (ii) a pharmaceutically acceptable carrier. This invention further provides a method for selectively reducing the number of senescent cells in a subject comprising administering to the subject the present composition. This invention further provides a method for selectively reducing the number of senescent cells in a subject’s skin comprising administering to the subject’s skin the present composition. Finally, this invention provides an article of manufacture comprising a face mask having releasably affixed thereto the present composition, wherein, when the subject wears the face mask, the composition is administered to the subject’s face. Detailed Description of the Invention This invention provides senolytic compositions and methods for ameliorating an array of aging hallmarks in a subject. Definitions In this application, certain terms are used which shall have the meanings set forth as follows. As used herein, “administer”, with respect to an agent, means to deliver the agent to a subject’s body via any known method. Specific modes of administration include, without limitation, oral, sublingual, parenteral, intraperitoneal, intravenous, intra-organ injection, intra-arterial, transdermal, topical, intramuscular, rectal, transbuccal, intranasal, liposomal, via inhalation, vaginal, intraocular, local (e.g., via catheter or stent), subcutaneous, intrathecal, or intra-adiposal administration. Preferably, the present compositions are administered topically (e.g., via direct contact with the skin). The present compositions can also be administered parenterally in the form of an intramuscular, intravenous, subcutaneous, intraperitoneal, local or transdermal bolus injection or continuous infusion. In addition, in this invention, the various compositions can be formulated using one or more routinely used pharmaceutically acceptable carriers. Such carriers are well known to those skilled in the art. For example, oral delivery systems include, for example, tablets, pills, capsules, granules, food bars, confectionery, and powders (such as powders that can be added to water to form a drinkable formulation). These can contain excipients such as binders (e.g., hydroxypropylmethyl-cellulose, polyvinyl pyrilodone, other cellulosic materials and starch), diluents (e.g., lactose and other sugars, starch, dicalcium phosphate and cellulosic materials), disintegrating agents (e.g., starch polymers and cellulosic materials) and lubricating agents (e.g., stearates and talc). In one embodiment, the oral delivery system is a powder and comprises one or more of xylitol, erythritol, malic acid, flavoring, silicon dioxide, calcium silicate, and rebaudioside A. In another embodiment, the oral delivery system is in liquid form as a solution, suspension, or emulsion, or in the form of a syrup, linctus, elixir, or a liquid beverage. Pharmaceutically acceptable carriers suitable for topical use (e.g., for use in a face mask, gel, or cream) include, without limitation, emollients which soften the skin and prevent excessive dryness. This may be important when senolytics are used, since senolytics can sometimes be drying or irritating. Such carriers also include, without limitation, emulsifiers which keep oil- and water-based ingredients stable and uniformly mixed, particularly in creamy or gel-based senolytic masks. Such carriers further include without limitation, film-forming agents which, in a peel-off senolytic mask, help create a layer that can be peeled away, lifting away dead skin cells. Such carriers further include, without limitation, humectants which attract and retain moisture, counteracting potential drying effects of senolysis. Such carriers further include, without limitation, occlusive / opacifying agents which seal moisture in and can also provide opacity to a mask, improving the skin’s appearance during its application. Such carriers still further include, without limitation, solvents which dissolve senolytics agents, making them easier to spread evenly over the skin. Finally, such carriers include, without limitation, texture enhancers which improve the spreadability and consistency of a senolytic mask to ensure uniform coverage and ease of application. As used herein, the term “aging hallmark” (used synonymously with “age-related hallmark” and “hallmark related to aging”) includes, without limitation, any of genomic instability, telomere attrition, an epigenetic alteration, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, transcriptomic dysregulation, crosslinking, and altered intercellular communication. These hallmarks are known, and reviewed in depth by C. López Otín, et al. (7). As used herein, the term “ameliorate”, when used in reference to an aging hallmark, includes, without limitation, (i) slowing, stopping, reversing, or preventing the hallmark's progression, (ii) slowing, stopping, reversing, or preventing the progression of the hallmark’s symptoms, (iii) preventing or reducing the likelihood of the hallmark’s recurrence, and / or (iv) preventing or reducing the likelihood that the hallmark’s symptoms will recur. In one embodiment, treating a subject afflicted with an aging hallmark means (i) reversing the hallmark's progression, ideally to the point of eliminating the hallmark, and / or (ii) reversing the progression of the hallmark’s symptoms, ideally to the point of eliminating the symptoms. As used herein, “Bcl inhibitors”, such as Bcl-2, Bcl-xt, and Bcl-w inhibitors, include, without limitation, Aloperine, 6-shogoal, Alteichin, Alterperylenol, Altertoxin I, Altertoxin II, Apogossypol, beta-Asarone, beta-Sitosterol, Curcumin, Dihydromyricetin, Fisetin, Galangin, Genistein, Gingerenone A, Gossypol, Illamycin E, Isoledene, Jacarelhyperol A, Kongensin A, Kongensin A, Ligustilide, Luteolin, Meiogynin A, Phenazine-1- carboxamide, Sanguinarine, Tanshinone IIA, and Quercetin. As used herein, “Bcl-2 inhibitors” include, without limitation, Alteichin, Aloperine, Altertoxin I, Altertoxin II, Apogossypol, beta-Sitosterol, Fisetin, Galangin, Gossypol, Gossypol, Illamycin E, Jacarelhyperol A, Luteolin, and Quercetin. As used herein, “BET inhibitors” include, without limitation, Amentoflavone, Aristoyagonine, and Resveratrol. As used herein, “BH3 mimetics” include, without limitation, Hypericin, Gossypol, and Quercetin. As used herein, “bioavailability enhancers” includes, without limitation, DMSO, decyl methyl sulfoxide, N-dodecyl pyrrolidone, decanol, dodecanol, an organic acid such as oleic acid, zinc, vitamin C, piperine (Bioperine®) or the like, and combinations thereof. As used herein, “emollients” include, without limitation, Aleurites Moluccana Seed Oil; Alpha-Glucan Oligosaccharide; Apricot Kernel Oil; Argan Oil; Avocado Oil; Babassu Oil; Canola Oil; Caprooyl Phytosphingosine; Caprooyl Sphingosine; Carrot Oil; Ceramides; Chia seed oil; Cholesterol; Cocoa Butter; Cocos nucifera Fruit Extract; Cocos nucifera Fruit Extract; Echium plantagineum Seed Oil; Ectoin; Elaeis guineensis Oil; Evening Primrose Oil; Gamma Linolenic Acid (GLA); Glucosyl Ceramide; Glycine Soja Sterols; Hemp Seed Oil; Hydrogenated Olive Oil; Hydroxypalmitoyl Sphinganine; Jojoba Oil; Kukui Nut Oil; Linoleic Acid; Linseed Seed Oil; Manuka Oil; Meadowfoam Seed Oil; Moringa oleifera Seed Oil; Palm Oil; Passiflora edulis Seed Oil; Phytoceramides; Phytosphingosine; Phytosphingosine Phosphate; Pongamia Glabra Seed Oil; Prunus Domestica Seed Oil; Rapeseed Oil; Raphanus sativus Seed Oil; Rosa canina seed oil; Rose Hip Oil; Safflower Seed Oil; Sclerocarya Birrea Seed Oil; Sesame Seed oil; Silybum marianum Seed Oil; Soy Oil; Sphingolipids; Squalane; Squalene; Sunflower Seed Oil; and Sweet Almond Oil. As used herein, “emulsifiers” include, without limitation, Beheneth-5; Behentrimonium Chloride; Behentrimonium Chloride; C11-15 Pareth-7; C12-16 Pareth-9; C13-14 Isoalkane; C14-22 Alcohols; Candelilla / Jojoba / Rice Bran Polyglyceryl-3 Esters; Ceteareth-25; Ceteareth-6 Olivate; Cetearyl Glucoside; Cetearyl Olivate; DEA Oleth-10 Phosphate; Dicetyl Phosphate; Dihydrocholeth-30; Diisostearyl Polyglyceryl-3 Dimer Dilinoleate; Ethylhexyl Stearate; Glycereth-6 Laurate; Hydrogenated Styrene / Isoprene Copolymer; Laureth-3; Lauryl PEG-9 Polydimethylsiloxyethyl Dimethicone; PEG / PPG- 14 / 4 Dimethicone; PEG-32; Polyglyceryl-10 Caprylate / Caprate; Polyglyceryl-10 Dioleate; Polyglyceryl-3 Polyricinoleate; Polyglyceryl-6 Laurate; Polyglyceryl-6 Oleate; Potassium Stearate; Propylene Glycol Isoceteth-3 Acetate; Sesquioleate; Sodium Stearoyl Lactylate; Sorbitan Stearate; Sorbitan Tristearate; Steareth-2; Steareth-21; Tamarindus Indica Seed Gum; Trideceth-6; and Sorbitan Palmitate. As used herein, “film-forming agents” include, without limitation, Allyl Methacrylates Crosspolymer; biosaccharide gum-1; Capryloyl Glycerin / Sebacic Acid Copolymer; Di- PPG-3 Myristyl Ether Adipate; Ethylcellulose; Glyceryl Polymethacrylate; Hydroxypropyl Guar; Hydroxypropyl Methylcellulose; Polyacrylamide; Polyacrylate-17; Polyacrylate Crosspolymer; Polyester-8; Polyglucuronic Acid; Polyquaterniums; Polyvinylpyrrolidone; PPG-12 / SMDI Copolymer; PVM / MA Copolymer; PVP / Dimethylaminoethylmethacrylate; Rhizobian Gum; Sodium Carbomer; Sodium Carbomer; Sodium Polyacrylate; VA / Crotonates Copolymer; VP / Eicosene Copolymer; and VP / VA Copolymer. As used herein, “general senolytics” include, without limitation, 2,5-dimethylpyrazine, Caffeine, Coumestrol, Daidzein, Ergothienine, Ginsenoside, Isatis tinctoria, Licochalcone A, Quinidine, Solidago alpestris, Silymarin, Terreic acid, Withaferin A, Lipoic acid, Artemisinin, Honokiol, Magnolol, Niacinamide, and o-Vanillin. As used herein, “HDAC-6 inhibitors” include, without limitation, Psammaplin A, Burkholdac B, Romidepsin, Thailandepsin B, and Trichostatin A. As used herein, “HSP-90 inhibitors” include, without limitation, Colletofragarone A2, Celastrol, Conglobatin, Deguelin, Derrubone, Dihydroberberine, Falcarinol, Gedunin, Kongensin A, Radicicol, and Salidroside. As used herein, “humectants” include, without limitation, Glycerin; Glycoproteins; Honey; Hyaluronic Acid; Hydrolyzed Glycosamino-glycans; Lysine HCI; Myristyl Nicotinate; Polyglutamic Acid; Proline; Rhamnose; Sodium Acetylated Hyaluronate; Sodium Hyaluronate; Sodium Hyaluronate Crosspolymer; and Tranexamic Acid. As used herein, “Mcl-1 inhibitors” include, without limitation, Emodin, Luteolin, Withacnistin, Cosmomycin C, Bufalin, Thymoquinone, Wogonin, Chrysin, Norcantharidin, Celastrol, Ouabain, Digitoxin, and Quercetin. As used herein, “mitochondrial uncouplers” include, without limitation, pyrrolomycin C, phloretin, and salicyclic acid. As used herein, “occlusive opacifying agents” include, without limitation, Barium Sulfate; Glycol Distearate; Octyldodecanol; Oleyl Erucate; Ozokerite; Palmitic Acid; Palm Kernel Acid; Pentaerythrityl; Tetraoctanoate; and Tin Oxide. As used herein, “p53 / MDM2 inhibitors” include, without limitation, Curcumin, Chetomin, Dihydroberberine, Eupatilin, Fucoxanthin, Furcreastatin, Genistein, Ginsenoside RG3, Gossypol, Indole-3-carbinole, Melatonin, Origanum majorana, Oroxylin A, and Parthenolide. As used herein, “PI3K / AKT inhibitors” include, without limitation, 6’’- debromohamacanthin A, alpha-Mangostin, Andrographolide, Arctigenin, Bisbenzylisoquinoline, Cerberin, Cryptotanshinone, Curcumin, Fucosterol, Neolymphostin A, Piperlongumine, Salidroside, Sinulariolide, Vitexin, and Apigenin. As used herein, “selectively reducing the number of senescent cells” in a subject shall mean reducing (i.e., killing or otherwise removing) the number of cells in the subject, wherein the senescent cells present are reduced by a percentage greater than that by which non-senescent cells are reduced. For example, if an agent reduces a subject’s senescent cells by 10% and reduces the subject’s non-senescent cells by 5%, the agent selectively reduces the number of senescent cells in the subject. The following are non-limiting examples of selectively reducing the number of senescent cells in a subject: at least 5% of the cells so reduced are senescent cells; at least 10% of the cells so reduced are senescent cells; at least 15% of the cells so reduced are senescent cells; at least 20% of the cells so reduced are senescent cells; at least 25% of the cells so reduced are senescent cells; at least 30% of the cells so reduced are senescent cells; at least 35% of the cells so reduced are senescent cells; at least 40% of the cells so reduced are senescent cells; at least 45% of the cells so reduced are senescent cells; at least 50% of the cells so reduced are senescent cells; at least 55% of the cells so reduced are senescent cells; at least 60% of the cells so reduced are senescent cells; at least 65% of the cells so reduced are senescent cells; at least 70% of the cells so reduced are senescent cells; at least 75% of the cells so reduced are senescent cells; at least 80% of the cells so reduced are senescent cells; at least 85% of the cells so reduced are senescent cells; at least 90% of the cells so reduced are senescent cells; at least 95% of the cells so reduced are senescent cells; at least 96% of the cells so reduced are senescent cells; at least 97% of the cells so reduced are senescent cells; at least 98% of the cells so reduced are senescent cells; and at least 99% of the cells so reduced are senescent cells. Similarly, selectively reducing the number of senescent cells in a subject’s skin (e.g., facial skin) shall mean reducing (i.e., killing or otherwise eliminating) the number of cells in the subject’s skin wherein the senescent cells present are reduced by a percentage greater than that by which non-senescent cells are reduced. For example, if an agent reduces a subject’s senescent skin cells by 10% and reduces the subject’s non- senescent skin cells by 5%, the agent selectively reduces the number of senescent skin cells in the subject. The following are non-limiting examples of selectively reducing the number of senescent cells in a subject’s skin: at least 5% of the cells so reduced are senescent cells; at least 10% of the cells so reduced are senescent cells; at least 15% of the cells so reduced are senescent cells; at least 20% of the cells so reduced are senescent cells; at least 25% of the cells so reduced are senescent cells; at least 30% of the cells so reduced are senescent cells; at least 35% of the cells so reduced are senescent cells; at least 40% of the cells so reduced are senescent cells; at least 45% of the cells so reduced are senescent cells; at least 50% of the cells so reduced are senescent cells; at least 55% of the cells so reduced are senescent cells; at least 60% of the cells so reduced are senescent cells; at least 65% of the cells so reduced are senescent cells; at least 70% of the cells so reduced are senescent cells; at least 75% of the cells so reduced are senescent cells; at least 80% of the cells so reduced are senescent cells; at least 85% of the cells so reduced are senescent cells; at least 90% of the cells so reduced are senescent cells; at least 95% of the cells so reduced are senescent cells; at least 96% of the cells so reduced are senescent cells; at least 97% of the cells so reduced are senescent cells; at least 98% of the cells so reduced are senescent cells; and at least 99% of the cells so reduced are senescent cells. The following are additional non-limiting examples of selectively reducing the number of senescent cells in a subject: at least 5% of the subject’s senescent cells are reduced; at least 10% of the subject’s senescent cells are reduced; at least 15% of the subject’s senescent cells are reduced; at least 20% of the subject’s senescent cells are reduced; at least 25% of the subject’s senescent cells are reduced; at least 30% of the subject’s senescent cells are reduced; at least 35% of the subject’s senescent cells are reduced; at least 40% of the subject’s senescent cells are reduced; at least 45% of the subject’s senescent cells are reduced; at least 50% of the subject’s senescent cells are reduced; at least 55% of the subject’s senescent cells are reduced; at least 60% of the subject’s senescent cells are reduced; at least 65% of the subject’s senescent cells are reduced; at least 70% of the subject’s senescent cells are reduced; at least 75% of the subject’s senescent cells are reduced; at least 80% of the subject’s senescent cells are reduced; at least 85% of the subject’s senescent cells are reduced; at least 90% of the subject’s senescent cells are reduced; at least 95% of the subject’s senescent cells are reduced; at least 96% of the subject’s senescent cells are reduced; at least 97% of the subject’s senescent cells are reduced; at least 98% of the subject’s senescent cells are reduced; at least 99% of the subject’s senescent cells are reduced; and 100% of the subject’s senescent cells are reduced. Similarly, the following are additional non-limiting examples of selectively reducing the number of senescent skin cells in a subject: at least 5% of the subject’s senescent skin cells are reduced; at least 10% of the subject’s senescent skin cells are reduced; at least 15% of the subject’s senescent skin cells are reduced; at least 20% of the subject’s senescent skin cells are reduced; at least 25% of the subject’s senescent skin cells are reduced; at least 30% of the subject’s senescent skin cells are reduced; at least 35% of the subject’s senescent skin cells are reduced; at least 40% of the subject’s senescent skin cells are reduced; at least 45% of the subject’s senescent skin cells are reduced; at least 50% of the subject’s senescent skin cells are reduced; at least 55% of the subject’s senescent skin cells are reduced; at least 60% of the subject’s senescent skin cells are reduced; at least 65% of the subject’s senescent skin cells are reduced; at least 70% of the subject’s senescent skin cells are reduced; at least 75% of the subject’s senescent skin cells are reduced; at least 80% of the subject’s senescent skin cells are reduced; at least 85% of the subject’s senescent skin cells are reduced; at least 90% of the subject’s senescent skin cells are reduced; at least 95% of the subject’s senescent skin cells are reduced; at least 96% of the subject’s senescent skin cells are reduced; at least 97% of the subject’s senescent skin cells are reduced; at least 98% of the subject’s senescent skin cells are reduced; at least 99% of the subject’s senescent skin cells are reduced; and 100% of the subject’s senescent skin cells are reduced. As used herein, “senescent cells” are characterized by markers that include, without limitation, increased cell size, accumulation of lipofuscin, high expression of cell cycle regulators (e.g., pl6INK4A), p21CIPl, and senescence associated secretory phenotype (SASP) factors (including, without limitation, TNF-alpha, interleukin-6 (IL-6), multifunctional cytokine IL-lbeta, chemokines CXCL10, RANTES / CCL5, and MCP-1, matrix metalloprotease MMP3, and serine-protease inhibitor PAI-1 (Senescence Associated Secretory Phenotype (SASP): TNF-alpha, interleukin-6 (IL-6), the multifunctional cytokine IL-Ib, the chemokines CXCL10, RANTES / CCL5 and MCP-1, the matrix metalloprotease MMP3, and the serine-protease inhibitor PAI-1 (Tchkonia, et al., 2013 J Clin Invest 123, 966-72; Sun, et al., 2018 Trends Mol Med 24, 871-885; Rao and Jackson 2016 Trends Cancer 2:676-687)), increased cellular senescence- associated b-galactosidase (SA^gal) activity / accumulation of b-galactosidase, hemostatic factors (e.g., PAI-1), proteases, formation of senescence-associated heterochromatin foci (SAHF), and the appearance of senescent-associated distension of satellites (SADS) and telomere-associated DNA damage foci (TAFs) (Kirkland, et al., 2017 J Am Geriatr Soc 201765(10):2297-2301; Coppe, et al., 2010 ARP 5:99-118; Young and Narita, 2009 EMBO Rep 10:228-30). Senescence-associated secretory phenotype (SASP) refers to a phenotype that often develops in senescent cells, marking the dramatic changes in their secretome (Coppe, et al., 2010 ARP 5:99-118; Young and Narita 2009 TMBO Rep 10:228-30). It entails the release of pro-inflammatory cytokines, bradykines, and chemokines, prostanoids, miRNAs, damage-associated molecular pattern proteins (DAMPs), tissue-damaging proteases (i.e., metalloproteases (MMPs)), factors that impact stem and progenitor cell function, hemostatic factors, and growth factors (Kirkland, et al., 2017 J Am Geriatr Soc 201765(10):2297-2301). SASP factors include, without limitation, interleukins (IL-6, IL- 8, IL-1b), monocyte chemoattractant protein-1, and plasminogen-activated inhibitor-1. Senescent cell-associated molecules include those that are described in the art as comprising the senescence-associated secretory phenotype, senescent-messaging secretome, and DNA damage secretory program (DDSP). These groupings of senescent cell associated molecules, as described in the art, contain molecules in common and are not intended to describe three separate distinct groupings of molecules. Senescent cell-associated molecules include certain expressed and secreted growth factors, proteases, cytokines, and other factors that may have potent autocrine and paracrine activities (see, e.g., Coppe, et al., 2006 J. Biol. Chem. 281:29568-74; Coppe, et al., 2010 PLOS One 5:99-118; Krtolica, et al., 2001 PNAS USA.98:12072-77; Parrinello, et al., 2005 J. Cell Sci.118:485-96). Extracellular matrix (ECM)-associated factors include inflammatory proteins and mediators of ECM remodeling that are strongly induced in senescent cells (see, e.g., Kuilman, et al., 2009 Nature Reviews 9:81-94). Other senescent cell-associated molecules include extracellular polypeptides (proteins) described collectively as the DNA damage secretory program (DDSP) (see, e.g., Sun, et al., 2012 Nature 18:1359-1368). Senescent cell-associated proteins also include cell surface proteins (or receptors) that are expressed on senescent cells, which include proteins that are present at a detectably lower amount or are not present on the cell surface of a non-senescent cell. Senescent cell-associated proteins also include cell surface markers, like cluster differentiation markers, that have modified expression (loss or gain) during senescence progression of certain cell types (ex. CD26, CD28). Senescence cell-associated molecules include secreted factors that may make up the pro-inflammatory phenotype of a senescent cell (e.g., SASP). These factors include, without limitation, GM-CSF, GROa, GROo^y, IGFBP-7, IL-Ig, IL-6, IL-7, IL-8, MCP-1, MCP-2, MIP-la, MMP-1, MMP- 10, MMP-3, Amphiregulin, ENA-78, Eotaxin-3, GCP-2, GITR, HGF, ICAM-1, IGFBP-2, IGFBP-4, IGFBP-5, IGFBP-6, IL-13, IL-10, MCP-4, MIF, MIP-3a, MMP-12, MMP-13, MMP-14, NAP2, Oncostatin M, osteoprotegerin, PIGF, RANTES, sgpl30, TIMP-2, TRAIL-R3, Acrp30, angiogenin, Axl, bFGF, BLC, BTC, CTACK, EGF-R, Fas, FGF-7, G- CSF, GDNF, HCC-4, 1-309, IFN-g, IGFBP-1, IGFBP-3, IL-1 Rl, IL-11, IL-15, IL-2R-a, IL-6R, I-TAC, Leptin, LIF, MMP-2, MSP-a, PAI-1, PAI-2, PDGF-BB, SCF, SDF-1, sTNF RI, sTNF RII, Thrombopoietin, TIMP-1, tPA, uPA, uPAR, VEGF, MCP-3, IGF-1, TGF-3, MIP-1-d, IL-4, FGF-7, PDGF-BB, IL-16, BMP-4, MDC, MCP-4, IL-10, TIMP-1, Fit-3 Ligand, ICAM-1, Axl, CNTF, INFy, EGF, and BMP-6. Additional identified factors, which include those sometimes referred to in the art as senescence messaging secretome (SMS) factors, some of which are included in the listing of SASP polypeptides, include, without limitation, IGF1, IGF2, and IGF2R, IGFBP3, IDFBP5, IGFBP7, PA11, TGF-b, WNT2, IL-1 a, IL-6, IL-8, and CXCR2-binding chemokines. Cell-associated molecules also include, without limitation, the factors described in Sun, et al., Nature Medicine, and include, for example, products of the genes, MMP1, WNT16B, SFRP2, MMP12, SPINK1, MMP10, ENPP5, EREG, BMP6, ANGPTL4, CSGALNACT, CCL26, AREG, ANGPT1, CCK, THBD, CXCL14, NOV, GAL, NPPC, FAM150B, CST1, GDNF, MUCL1, NPTX2, TMEM155, EDN1, PSG9, AD AMTS 3, CD24, PPBP, CXCL3, MMP3, CST2, PSG8, PCOLCE2, PSG7, TNFSF15, C17orf67, CALCA, FGFJ8, IL8, BMP2, MATN3, TFP1, SERPINI 1, TNFRSF25, and IL23A (Coppe, et al., 2010 ARP 5:99-118; Young and Narita 2009 EMBO Rep 10:228-30; Basisty, et al., 2020 PLOS Biology 18(1):e300599). Senescent cell-associated proteins also include cell surface proteins (or receptors) that are expressed on senescent cells, which include proteins that are present at a detectably lower amount or are not present on the cell surface of a non-senescent cell. As used herein, a “skin penetration enhancer” includes, without limitation, DMSO, decyl methyl sulfoxide, N-dodecyl pyrrolidone, decanol, dodecanol, an organic acid such as oleic acid, zinc, vitamin C, piperine (Bioperine®) or the like, and combinations thereof. As used herein, “solvents” include, without limitation, Butyl Acetate; Butyloctanol; C13- 15 Alkane; C15-19 Alkane; C9-12 Alkane; Deionized / Demineralized Water; Dimethyl Capramide; Dimethyl Isosorbide; Ethoxydiglycol; Glycerol Triacetate; Hexylene Glycol; Hydrogenated Farnesene; Isobutyl Acetate; Isododecane; Isopentyldiol; Methylpropanediol; PEG / PPG-17 / 6 Copolymer; PEG / PPG-18 / 4 Copolymer; Polypropylene Glycol; PPG-14 Butyl Ether; Propanediol; Propylene Carbonate; Triacetin; Triethyl Citrate; and Triethylhexanoin. As used herein, the term “subject” includes, without limitation, a mammal such as a human, a non-human primate, a dog, a cat, a horse, a sheep, a goat, a cow, a rabbit, a pig, a rat, and a rodent (such as a mouse). Where the subject is human, the subject can be of any age. For example, the subject can be 60 years or older, 65 or older, 70 or older, 75 or older, 80 or older, 85 or older, or 90 or older. Alternatively, the subject can be 50 years or younger, 45 or younger, 40 or younger, 35 or younger, 30 or younger, 25 or younger, or 20 or younger. As used herein, “texture enhancers” include, without limitation, Chitosan; Diheptyl succinate; Ethylhexyl Methoxycrylene; and Mallow. As used herein, “TLR-1, -2, and / or -4 inhibitors” include, without limitation, 6-shogoal, 1- palmitoyl-2-oleoylphosphatidylglycerol, Aesculus hippocastanum, Allium ursinum, Alpinia officinarum, Andrographolide, Arctostaphylos uva-ursi, Baicalein, beta- Sitosterol, Bilobalide, Boswellia serrata, Cantharidin, Castanea sativa, Catalpol, Chlorella pyrenoidosa, Cinchona pubescens, Cinnamomum verum, Costunolide, Curcumin, Cynara scolymus, Dehydrocholic acid, Dihydroartemisinin, Filipendula ulmaria, Gentiana lutea, Ginkgo biloba, Ginkgolides, Girolline, Glycyrrhiza glabra, Hamamelis virginiana, Harpagide, Hesperetin, Humulus lupulus, Hybanthus enneaspermus, Hypericum perforatum, Isoalantolactone, Isofraxidin, Luteolin, Madecassoside, Mangifera indica, Mucuna pruriens, Mumefural, Myristica fragrans, Okanin, Oxymatrine, Pedalium murex, Phloretin, Phoenix sylvestris, Phosphatidylglycerol, Piper betle, Polygalasaponin F, Pueraria tuberosa, Purpurogallin, Quercus robur, Rheum palmatum, Robinin, Rotenone, Salix alba, Salvia officinalis, Schaftoside, Sida cordifolia, Siegesbeckia pubescens Makino, Sparstolonin B, Sphaeranthu indicues, Spirulina, Syzygium aromaticum, Syzygium cumini, Taspine, Terminalia chebula, Tinospora cordifolia, Tribulis terrestris, Trichosanthes dioica (fruit), Usnea barbata, Vigna radiata, Vitis vinifera, Withania somnifera, Zingiber officinale, and Quercetin. Embodiments of the Invention This invention provides compositions and methods for ameliorating aging hallmarks. These compositions comprise certain combinations of senolytic agents that act together to accomplish this goal, especially in skin. The invention also provides related articles of manufacture. Specifically, this invention provides a composition comprising (i) a first agent selected from the group consisting of a BH3 mimetic, an HDAC6 inhibitor, and a TLR-1, -2, and / or -4 inhibitor, and (ii) a second agent selected from the group consisting of a mitochondrial uncoupler, a Bcl-2 inhibitor, a p53 / MDM2 inhibitor, a HSP-90 inhibitor, a PI3K / AKT inhibitor, a BET inhibitor, and a general senolytic. In one embodiment, the present composition further comprises at least one additional agent selected from the group consisting of a BH3 mimetic, an Mcl-1 inhibitor, a TLR-1, -2, and / or -4 inhibitor, a p53 / MDM2 inhibitor, a PI3K / AKT inhibitor, an HSP-90 inhibitor, a BET inhibitor, and a Bcl-2 inhibitor. In another embodiment, the present composition further comprises at least one additional agent selected from the group consisting of a mitochondrial uncoupler, a BH3 mimetic, an Mcl-1 inhibitor, an HSP-90 inhibitor, a PI3K / AKT inhibitor, a BET inhibitor, and a Bcl-2 inhibitor. In another embodiment, the present composition further comprises at least one additional agent selected from the group consisting of a mitochondrial uncoupler and a BH3 mimetic. In another embodiment, the present composition further comprises an additional agent which is a mitochondrial uncoupler. In another embodiment, the present composition further comprises (i) at least one additional agent selected from the group consisting of a BH3 mimetic, an Mcl-1 inhibitor, a TLR-1, -2, and / or -4 inhibitor, a p53 / MDM2 inhibitor, a PI3K / AKT inhibitor, an HSP-90 inhibitor, a BET inhibitor, a general senolytic, and a Bcl-2 inhibitor; (ii) at least one additional agent selected from the group consisting of a mitochondrial uncoupler, a BH3 mimetic, an Mcl-1 inhibitor, an HSP-90 inhibitor, a PI3K / AKT inhibitor, a BET inhibitor, and a Bcl-2 inhibitor; (iii) at least one additional agent selected from the group consisting of a mitochondrial uncoupler and a BH3 mimetic; and / or (iv) an additional agent which is a mitochondrial uncoupler. The various agents in the present composition are commercially available. Below, exemplary dosage ranges are provided for various preferred embodiments of Bcl inhibitors, Bcl-2 inhibitors, BET inhibitors, BH3 mimetics, general senolytics, HDAC- 6 inhibitors, HSP-90 inhibitors, Mcl-1 inhibitors, mitochondrial uncouplers, p53 / MDM2 inhibitors, PI3K / AKT inhibitors, and TLR-1, -2, and / or -4 inhibitors. Each dosage range is presented as a sequence of three numbers in parentheses. These numbers represent, from left to right, the minimum concentration (%) (e.g., the minimum concentration at which the agent would be expected to have therapeutic value), the preferred concentration (%) (e.g., a concentration at which the agent would be expected to have significant therapeutic value), and the maximum concentration (%, where % represents the percent of the total formulation weight) (e.g., the maximum concentration at which the agent would be expected to be non-toxic). For example, a dosage rage of “(0.01, 0.1, 30)” means a minimum concentration of 0.01%, a preferred concentration of 0.1%, and a maximum concentration of 30%. Exemplary Bcl inhibitor dosage ranges include, without limitation, Aloperine (0.1, 1, 30), 6-shogoal (0.01, 0.1, 30), Alteichin (0.01, 0.1, 30), Alterperylenol (0.01, 0.1, 30), Altertoxin I (0.01, 0.1, 30), Altertoxin II (0.01, 0.1, 30), Apogossypol (0.01, 0.1, 30), beta-Asarone (0.01, 0.05, 30), beta-Sitosterol (0.1, 1, 30), Curcumin (0.5, 5, 30), Dihydromyricetin (0.01, 0.1, 30), Fisetin (0.1, 1, 30), Galangin (0.01, 0.1, 30), Genistein (0.1, 1, 30), Gingerenone A (0.01, 0.1, 30), Gossypol (0.01, 0.1, 30), Illamycin E (0.01, 0.1, 30), Isoledene (0.01, 0.1, 30), Jacarelhyperol A (0.01, 0.1, 30), Kongensin A (0.01, 0.1, 30), Kongensin A (0.01, 0.1, 30), Ligustilide (0.01, 0.1, 30), Luteolin (0.1, 1, 30), Meiogynin A (0.01, 0.1, 30), Phenazine-1-carboxamide (0.01, 0.1, 30), Sanguinarine (0.01, 0.1, 30), Tanshinone IIA (0.01, 0.1, 30), and Quercetin (0.1, 2, 30). Exemplary Bcl-2 inhibitor dosage ranges include, without limitation, Alteichin (0.01, 0.1, 30), Aloperine (0.1, 1, 30), Altertoxin I (0.01, 0.1, 30), Altertoxin II (0.01, 0.1, 30), Apogossypol (0.01, 0.1, 30), beta-Sitosterol (0.1, 1, 30), Fisetin (0.1, 1, 30), Galangin (0.01, 0.1, 30), Gossypol (0.01, 0.1, 30), Gossypol (0.01, 0.1, 30), Illamycin E (0.01, 0.1, 30), Jacarelhyperol A (0.01, 0.1, 30), Luteolin (0.1, 1, 30), and Quercetin (0.1, 2, 30). Exemplary BET inhibitor dosage ranges include, without limitation, Amentoflavone (0.01, 0.1, 30), Aristoyagonine (0.01, 0.1, 30), and Resveratrol (0.1, 1, 30). Exemplary BH3 mimetic dosage ranges include, without limitation, Hypericin (0.1, 1, 30), Gossypol (0.01, 0.1, 30), and Quercetin (0.1, 2, 30). Exemplary general senolytic dosage ranges include, without limitation, 2,5- dimethylpyrazine (0.01, 0.1, 30), Caffeine (0.1, 5, 30), Coumestrol (0.01, 0.1, 30), Daidzein (0.1, 1, 30), Ergothienine (0.01, 0.1, 30), Ginsenoside (0.01, 0.1, 30), Isatis tinctoria (0.01, 0.1, 30), Licochalcone A (0.1, 1, 30), Quinidine (0.01, 0.1, 30), Solidago alpestris (0.01, 0.1, 30), Silymarin (0.1, 1, 30), Terreic acid (0.01, 0.1, 30), Withaferin A (0.01, 0.1, 30), Lipoic acid (0.5, 5, 30), Artemisinin (0.01, 0.1, 30), Honokiol (0.1, 1, 30), Magnolol (0.1, 1, 30), Niacinamide (2, 5, 30), and o-Vanillin (0.01, 0.1, 30). Exemplary HDAC-6 inhibitor dosage ranges include, without limitation, Psammaplin A (0.01, 0.1, 30), Burkholdac B (0.01, 0.1, 30), Romidepsin (0.01, 0.1, 30), Thailandepsin B (0.01, 0.1, 30), and Trichostatin A (0.01, 0.1, 30). Exemplary HSP-90 inhibitor dosage ranges include, without limitation, Colletofragarone A2 (0.01, 0.1, 30), Celastrol (0.01, 0.1, 30), Conglobatin (0.01, 0.1, 30), Deguelin (0.01, 0.1, 30), Derrubone (0.01, 0.1, 30), Dihydroberberine (0.1, 1, 30), Falcarinol (0.01, 0.1, 30), Gedunin (0.01, 0.1, 30), Kongensin A (0.01, 0.1, 30), Radicicol (0.01, 0.1, 30), and Salidroside (0.1, 1, 30). Exemplary Mcl-1 inhibitor dosage ranges include, without limitation, Emodin (0.01, 0.1, 30), Luteolin (0.1, 1, 30), Withacnistin (0.01, 0.1, 30), Cosmomycin C (0.01, 0.1, 30), Bufalin (0.01, 0.1, 30), Thymoquinone (0.1, 1, 30), Wogonin (0.01, 0.1, 30), Chrysin (0.1, 1, 30), Norcantharidin (0.01, 0.1, 30), Celastrol (0.01, 0.1, 30), Ouabain (0.01, 0.1, 30), Digitoxin (0.01, 0.1, 30), and Quercetin (0.1, 2, 30). Exemplary mitochondrial uncoupler dosage ranges include, without limitation, pyrrolomycin C (0.01, 0.1, 30), phloretin (0.1, 1, 30), and salicyclic acid (0.5, 5, 30). Exemplary p53 / MDM2 inhibitor dosage ranges include, without limitation, Curcumin (0.5, 5, 30), Chetomin (0.01, 0.1, 30), Dihydroberberine (0.1, 1, 30), Eupatilin (0.01, 0.1, 30), Fucoxanthin (0.01, 0.1, 30), Furcreastatin (0.01, 0.1, 30), Genistein (0.1, 1, 30), Ginsenoside RG3 (0.01, 0.1, 30), Gossypol (0.01, 0.1, 30), Indole-3-carbinole (0.1, 1, 30), Melatonin (0.1, 2, 30), Origanum majorana (0.01, 0.1, 30), Oroxylin A (0.01, 0.1, 30), and Parthenolide (0.01, 0.1, 30). Exemplary PI3K / AKT inhibitor dosage ranges include, without limitation, 6’’- debromohamacanthin A (0.01, 0.1, 30), alpha-Mangostin (0.1, 1, 30), Andrographolide (0.01, 0.1, 30), Arctigenin (0.01, 0.1, 30), Bisbenzylisoquinoline (0.01, 0.1, 30), Cerberin (0.01, 0.1, 30), Cryptotanshinone (0.01, 0.1, 30), Curcumin (0.5, 5, 30), Fucosterol (0.01, 0.1, 30), Neolymphostin A (0.01, 0.1, 30), Piperlongumine (0.01, 0.1, 30), Salidroside (0.1, 1, 30), Sinulariolide (0.01, 0.1, 30), Vitexin (0.01, 0.1, 30), and Apigenin (0.1, 1, 30). Exemplary TLR-1, -2, and -4 inhibitor dosage ranges include, without limitation, 6- shogoal (0.01, 0.1, 30), 1-palmitoyl-2-oleoylphosphatidylglycerol (0.01, 0.1, 30), Aesculus hippocastanum (0.1, 1, 30), Allium ursinum (0.01, 0.1, 30), Alpinia officinarum (0.1, 1, 30), Andrographolide (0.01, 0.1, 30), Arctostaphylos uva-ursi (0.1, 1, 30), Baicalein (0.01, 0.1, 30), beta-Sitosterol (0.1, 1, 30), Bilobalide (0.01, 0.1, 30), Boswellia serrata (0.1, 1, 30), Cantharidin (0.01, 0.1, 30), Castanea sativa (0.01, 0.1, 30), Catalpol (0.01, 0.1, 30), Chlorella pyrenoidosa (0.1, 1, 30), Cinchona pubescens (0.01, 0.1, 30), Cinnamomum verum (0.01, 0.1, 30), Costunolide (0.01, 0.1, 30), Curcumin (0.5, 5, 30), Cynara scolymus (0.01, 0.1, 30), Dehydrocholic acid (0.01, 0.1, 30), Dihydroartemisinin (0.01, 0.1, 30), Filipendula ulmaria (0.01, 0.1, 30), Gentiana lutea (0.01, 0.1, 30), Ginkgo biloba (0.1, 1, 30), Ginkgolides (0.01, 0.1, 30), Girolline (0.01, 0.1, 30), Glycyrrhiza glabra (0.1, 1, 30), Hamamelis virginiana (0.1, 1, 30), Harpagide (0.01, 0.1, 30), Hesperetin (0.01, 0.1, 30), Humulus lupulus (0.01, 0.1, 30), Hybanthus enneaspermus (0.01, 0.1, 30), Hypericum perforatum (0.1, 1, 30), Isoalantolactone (0.01, 0.1, 30), Isofraxidin (0.01, 0.1, 30), Luteolin (0.1, 1, 30), Madecassoside (0.1, 1, 30), Mangifera indica (0.01, 0.1, 30), Mucuna pruriens (0.01, 0.1, 30), Mumefural (0.01, 0.1, 30), Myristica fragrans (0.01, 0.1, 30), Okanin (0.01, 0.1, 30), Oxymatrine (0.01, 0.1, 30), Pedalium murex (0.01, 0.1, 30), Phloretin (0.1, 1, 30), Phoenix sylvestris (0.01, 0.1, 30), Phosphatidylglycerol (0.01, 0.1, 30), Piper betle (0.01, 0.1, 30), Polygalasaponin F (0.01, 0.1, 30), Pueraria tuberosa (0.1, 1, 30), Purpurogallin (0.01, 0.1, 30), Quercus robur (0.01, 0.1, 30), Rheum palmatum (0.01, 0.1, 30), Robinin(0.01, 0.1, 30), Rotenone (0.01, 0.1, 30), Salix alba (0.1, 1, 30), Salvia officinalis (0.01, 0.1, 30), Schaftoside (0.01, 0.1, 30), Sida cordifolia (0.01, 0.1, 30), Siegesbeckia pubescens Makino (0.01, 0.1, 30), Sparstolonin B (0.01, 0.1, 30), Sphaeranthu indicues (0.01, 0.1, 30), Spirulina (0.1, 1, 30), Syzygium aromaticum (0.01, 0.1, 30), Syzygium cumini (0.01, 0.1, 30), Taspine (0.01, 0.1, 30), Terminalia chebula (0.01, 0.1, 30), Tinospora cordifolia (0.01, 0.1, 30), Tribulis terrestris (0.01, 0.1, 30), Trichosanthes dioica (fruit) (0.01, 0.1, 30), Usnea barbata (0.01, 0.1, 30), Vigna radiata (0.01, 0.1, 30), Vitis vinifera (0.01, 0.1, 30), Withania somnifera (0.01, 0.1, 30), Zingiber officinale (0.1, 1, 30), and Quercetin (0.1, 2, 30). In a preferred embodiment of the present composition, one or more of the agents in the composition is formulated for delayed release and / or extended release. In one embodiment of the present composition, the BH3 mimetic is formulated for delayed and / or extended release. In another embodiment, the HDAC6 inhibitor is formulated for delayed and / or extended release. In another embodiment, the TLR-1, -2, and / or -4 inhibitor is formulated for delayed and / or extended release. In another embodiment, the mitochondrial uncoupler is formulated for delayed and / or extended release. In another embodiment, the Bcl-2 inhibitor is formulated for delayed and / or extended release. In another embodiment, the p53 / MDM2 inhibitor is formulated for delayed and / or extended release. In another embodiment, the HSP-90 inhibitor is formulated for delayed and / or extended release. In another embodiment, the PI3K / AKT inhibitor is formulated for delayed and / or extended release. In another embodiment, the BET inhibitor is formulated for delayed and / or extended release. In another embodiment, the general senolytic is formulated for delayed and / or extended release. Additional embodiments of the present composition are set forth below in the Examples section. This invention also provides a composition comprising (i) the present composition and (ii) a pharmaceutically acceptable carrier. Preferably, each of these forms is self- administered twice daily, daily, every two days, twice per week, or once per week. In a preferred embodiment, the present composition is suitable for dermal administration (e.g., via microneedling, RF (Radio Frequency), or NIR (Near-Infrared Radiation)). In another preferred embodiment, the present composition comprises one or more bioavailability enhancers and / or one or more skin penetration enhancers. In one embodiment, the present composition is in a form selected from the group consisting of a food, a nutritional supplement, a nutraceutical, an injectable, and a skincare product. In a preferred embodiment, the present skincare product is in the form of a skin cream, serum, gel, aqueous solution, suspension, ointment, sprayable formulation, transdermal patch, or bandage. In another preferred embodiment, the present skincare product is in the form of a facial skin cream, a facial serum, a facial gel, a facial aqueous solution, a facial suspension, a facial ointment, a facial sprayable formulation, a facial transdermal patch, or a facial bandage. In a further preferred embodiment, the present skincare product is in the form of a scalp skin cream, a scalp serum, a scalp gel, a scalp aqueous solution, a scalp suspension, a scalp ointment, a scalp sprayable formulation, a scalp transdermal patch, or a scalp bandage. In a further preferred embodiment, the present skincare product is a face mask. Therapeutic face masks and methods for making and using them are known. This invention further provides a method for selectively reducing the number of senescent cells in a subject comprising administering to the subject the present composition. In one embodiment, the subject treated by the present method has a senescent cell percentage (i.e., the percentage of cells that are senescent) of, for example, at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, or at least 15%. The senescent cells include, for example, liver-related cells such as hepatocytes and pancreatic stellate cells; adipose tissue-related cells such as preadipocytes and adipose-derived stromal / progenitor cells; vascular-related cells such as endothelial cells and smooth muscle cells, specifically vascular smooth muscle cells (VSMCs); connective tissue-related cells such as fibroblasts, carcinoma-associated fibroblasts (CAFs), osteoblasts, osteoclasts, chondrocytes, myocytes, skeletal muscle cells, satellite cells, myoblasts, mesenchymal (stem) cells, and periodontal cells; nervous system-related cells such as neurons, astrocytes, and Schwann cells; immune-related cells such as macrophages, T cells, B cells, and natural killer (NK) cells; progenitor cells such as endothelial progenitor cells, fibroadipogenic progenitors (FAPs), neural progenitor cells (NPCs), liver-derived progenitor cells (LDPCs), mesenchymal progenitor cells (MPCs), cardiac progenitor cells (CPGs), hematopoietic progenitor cells, vascular smooth muscle cells, and cardiac progenitor cells; blood-related cells such as erythrocytes; skin-related cells such as keratinocytes and melanocytes; epithelial cells such as retinal pigment epithelial cells, biliary epithelial cells, thymic epithelial cells, lung epithelial cells, and mammary epithelial cells; gland-related cells such as acinar cells; and other cells such as retinal cells, beta cells, ovarian cells, and hematopoietic stem cells. In one embodiment, the senescent cells are liver-related cells such as hepatocytes and pancreatic stellate cells. In a further embodiment, the senescent cells are adipose tissue-related cells such as preadipocytes and adipose- derived stromal / progenitor cells. In a further embodiment, the senescent cells are vascular-related cells such as endothelial cells and smooth muscle cells, specifically vascular smooth muscle cells (VSMCs). In a further embodiment, the senescent cells are connective tissue-related cells such as fibroblasts, carcinoma-associated fibroblasts (CAFs), osteoblasts, osteoclasts, chondrocytes, myocytes, skeletal muscle cells, satellite cells, myoblasts, mesenchymal (stem) cells, and periodontal cells. In a further embodiment, the senescent cells are nervous system-related cells such as neurons, astrocytes, and Schwann cells. In a further embodiment, the senescent cells are immune-related cells such as macrophages, T cells, B cells, and natural killer (NK) cells. In a further embodiment, the senescent cells are progenitor cells such as endothelial progenitor cells, fibroadipogenic progenitors (FAPs), neural progenitor cells (NPCs), liver-derived progenitor cells (LDPCs), mesenchymal progenitor cells (MPCs), cardiac progenitor cells (CPGs), hematopoietic progenitor cells, vascular smooth muscle cells, and cardiac progenitor cells. In a further embodiment, the senescent cells are blood-related cells such as erythrocytes. In a further embodiment, the senescent cells are skin-related cells such as keratinocytes and melanocytes. In a further embodiment, the senescent cells are epithelial cells such as retinal pigment epithelial cells, biliary epithelial cells, thymic epithelial cells, lung epithelial cells, and mammary epithelial cells. In a further embodiment, the senescent cells are gland-related cells such as acinar cells. In a further embodiment, the senescent cells are other cells such as retinal cells, beta cells, ovarian cells, and hematopoietic stem cells. This invention further provides a method for selectively reducing the number of senescent cells in a subject’s skin comprising administering to the subject’s skin the present composition. In one embodiment, the subject’s skin treated by the present methods can have a senescent cell percentage (i.e., the percentage of skin cells that are senescent) of, for example, at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, or at least 15%. In a preferred embodiment, the present method comprises topically administering the composition to the subject’s skin. In another preferred embodiment, the present method comprises topically administering the composition to the subject’s face. In another preferred embodiment, the present method comprises topically administering the composition to the subject’s hands, neck, scalp, and / or décolleté area. This invention further provides a method for treating a disorder in a subject comprising administering to the subject the present composition, wherein the disorder is selected from the group consisting of one or more of the following: (i) a skin disorder such as sagging, wrinkles, loss of skin elasticity, skin ageing, low skin moisture, wounds, acne, skin darkening, skin whitening, undesired pigmentation, age-spots, loss of radiance, puffiness, uneven skin tone, redness, rosacea, loss of barrier function, loss of skin resilience, loss of firmness, stretch-marks, cellulite, and dryness; (ii) age-related skin conditions, skin conditions related to sun exposure, skin conditions related to pollution exposure, skin conditions related to oxidative stress, and skin conditions related to lifestyle choices such as diet, alcohol, and / or smoking; (iii) skin conditions related to inflammatory skin disorders and skin conditions related autoimmune disease skin disorders, such acne, asteatotic eczema, atopic dermatitis, contact dermatitis, discoid eczema, eczematous drug eruptions, erythema multiforme, erythroderma, gravitational / varicose eczema, hand eczema, keratosis lichenoides chronica, lichen nitidus, lichen planus, lichen simplex, lichen striatus, mycosis fimgoides, pityriasis lichenoides, psoriasis, seborrheic dermatitis, Stevens-Johnson Syndrome, toxic epidermal necrolysis, and vasculitis; (iv) alopecia areata, bullous pemphigoid, dermatomyositis, dystrophic epidermolysis bullosa, eosinophilic fasciitis, pemphigus vulgaris, pyoderma gangrenosum, scleroderma, systemic lupus erythematosus, and vitiligo; (v) increased frailty, loss of resilience, loss of muscle strength, loss of muscle endurance, loss of energy, loss of cognitive sharpness, and loss of memory; (vi) atherosclerosis, cardiovascular disease, cancer, arthritis, cataracts, osteoporosis, type 2 diabetes, hypertension, Alzheimer's disease, and glomerulosclerosis / decline in renal function; and (vii) actinic keratoses, freckles, lentigines or age spots, moles, photosensitivity, polymorphous light eruption, seborrheic keratoses, skin cancer (such as melanoma, squamous cell carcinoma, and basal cell carcinoma), solar elastosis, wrinkles, and sun burn. This invention further provides a method for treating a disorder in a subject comprising administering to the subject the present composition, wherein the disorder is selected from the group consisting of genomic instability, telomere attrition, an epigenetic alteration, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, transcriptomic dysregulation, crosslinking, and altered intercellular communication. In one embodiment, the present method ameliorates genomic instability. In another embodiment, the present method ameliorates telomere attrition. In another embodiment, the present method ameliorates one or more epigenetic alterations. In another embodiment, the present method ameliorates loss of proteostasis. In another embodiment, the present method ameliorates deregulated nutrient sensing. In another embodiment, the present method ameliorates mitochondrial dysfunction. In another embodiment, the present method ameliorates cellular senescence. In another embodiment, the present method ameliorates stem cell exhaustion. In another embodiment, the present method ameliorates transcriptomic dysregulation. In another embodiment, the present method ameliorates crosslinking. In another embodiment, the present method ameliorates altered intercellular communication. In a further embodiment of the present method, the method ameliorates at least two aging hallmarks in the subject. In another embodiment, the present method ameliorates at least three aging hallmarks in the subject. In another embodiment, the present method ameliorates at least four aging hallmarks in the subject. In another embodiment, the present method ameliorates at least five aging hallmarks in the subject. In another embodiment, the present method ameliorates at least six aging hallmarks in the subject. In another embodiment, the present method ameliorates at least seven aging hallmarks in the subject. In another embodiment, the present method ameliorates at least eight aging hallmarks in the subject. In another embodiment, the present method ameliorates at least nine aging hallmarks in the subject. In another embodiment, the present method ameliorates at least ten aging hallmarks in the subject. In another embodiment, the present method ameliorates at least eleven aging hallmarks in the subject. For example, in one embodiment, the present method ameliorates at least the following aging hallmarks in the subject: genomic instability, an epigenetic alteration, and loss of proteostasis. In another embodiment, the present method ameliorates at least the following aging hallmarks in the subject: an epigenetic alteration, loss of proteostasis, and mitochondrial dysfunction. In another embodiment, the present method ameliorates at least the following aging hallmarks in the subject: an epigenetic alteration, loss of proteostasis, and deregulated nutrient sensing. In another embodiment, the present method ameliorates cellular senescence or reduces the amount of senescent cells. In another embodiment, the present method ameliorates cellular senescence and stem cell exhaustion. In another embodiment, the present method ameliorates mitochondrial dysfunction and loss of proteostasis. In another embodiment, the present method ameliorates epigenetic alterations and loss of proteostasis. In another embodiment, the present method ameliorates altered intercellular communication and deregulated nutrient sensing. In another embodiment, the present method ameliorates altered intercellular communication and stem cell exhaustion. In another embodiment, the present method ameliorates stem cell exhaustion and epigenetic alterations. In another embodiment, the present method ameliorates epigenetic alterations and mitochondrial dysfunction. In another embodiment, the present method ameliorates epigenetic alterations, loss of proteostasis, and mitochondrial dysfunction. In another embodiment, the present method ameliorates stem cell exhaustion, cellular senescence, and altered intercellular communication. In another embodiment, the present method ameliorates epigenetic alterations, cellular senescence, and mitochondrial dysfunction. In another embodiment, the present method ameliorates deregulated nutrient sensing, mitochondrial dysfunction, and loss or proteostasis. In another embodiment, the present method ameliorates epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, and cellular senescence. Also envisioned in this invention is administering to a subject the present composition in order to accomplish one or more of the following objectives: (i) increasing lifespan, lengthening healthspan, and / or improving stress resistance; (ii) slowing down aging; (iii) reducing, mitigating, andor slowing down aging-related diseases, aging-related symptoms, and / or age-related impairments; (iv) reducing the risk of, preventing, inhibiting the onset of, or treating a disease such as cardiovascular disease (e.g., atherosclerosis, high blood pressure, cardiac failure, cardiac hypertrophy, coronary syndrome, heart valve dysfunction, calcification of arteries and valves, or stroke), metabolic dysregulation (e.g., metabolic syndrome, high blood cholesterol, high serum triglycerides, increased serum HbA1c, insulin resistance, insulin resistance disorder, hyperglycemia, reduced insulin sensitivity, diabetes, obesity, a thyroid disorder, metabolic syndrome, fatty liver, steatohepatitis, hepatic steatosis, or diabetic retinopathy), cancer, cachexia, frailty, sarcopenia, neurodegenerative disease (e.g., Alzheimer’s disease, vascular dementia, Lewy-body disease, frontotemporal dementia, Parkinson disease, mild cognitive impairment, amyotrophic lateral sclerosis, or Huntington's disease), neuropathy, eye disease (e.g., macular degeneration or cataract), lethargy, musculoskeletal diseases (e.g., rheumatoid arthritis, osteoarthritis, osteoporosis, or muscular dystrophy), lung diseases (e.g., lung fibrosis, chronic obstructive pulmonary disease (COPD), emphysema, aging-related increased susceptibility to lung infections including pneumonia), aging-related gastro-intestinal diseases (e.g., constipation, decreased stomach and gut motility, gastroparesis, polyps, gut dysbiosis, colitis, or inflammatory bowel disease), blood diseases (e.g., leukemia, lymphoma, anemia, platelet disorders, coagulation disorders, multiple myeloma, myelodysplastic syndromes, or myeloproliferative disorders), infertility, reduced fertility, aging-related increased risk of cancer or proliferative diseases, disorders caused or exacerbated by senescent cells, aging-related skin diseases, psoriasis, aging-related kidney diseases, sepsis, or sleep disorders; (v) improving and / or or mitigating the cellular and organismal physiological stress and dysfunction caused by surgery, exercise, combat, or certain work environments; and (vi) inhibiting the origin and progression of weight gain, wrinkles, sagging skin, aged skin, reduced stamina, reduced eyesight, reduced hearing, sarcopenia (i.e., a decrease in muscle mass), insulin resistance, fat deposition (e.g., abdominal fat deposition), hair graying, hair loss, baldness, loss of libido, erectile dysfunction, memory problems, reduced cognition, concentration problems, memory problems, sleep disorders, or mood disorders. This invention further provides a method for ameliorating at least one aging hallmark in a cell (e.g., a skin cell (such as a keratinocyte, fibroblast, or melanocyte), a skin stem cell, an endothelial cell, a neuron, a liver cell, a retinal cell, a hematopoetic stem cell, a muscle cell, a satellite cell, a hepatocyte, a chondrocyte, a cardiocyte, a white blood cell (such as a B cell, T cell, lymphocyte, or monocyte), or a gastrointestinal cell) comprising contacting the cell with the present composition, wherein the aging hallmark is selected from the group consisting of genomic instability, telomere attrition, an epigenetic alteration, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, transcriptomic dysregulation, crosslinking, and altered intercellular communication. The present method is envisioned for this cell- based embodiment, mutatis mutandis, as it is for the subject treatment embodiment in this invention. In the preferred embodiment of the present methods, the subject is a human. In another embodiment of the present methods, the subject is a rodent, a rabbit, a cat, a dog, or a horse. Measuring the number and percentage of senescent cells before and after treatment with the present compositions can be performed according to any known suitable method for doing so. Two common methods are measuring reduced senescence markers and a reduction in biological age as measured by DNA methylation. (https: / / www.nature.com / articles / s41514-023-00109-1) Finally, this invention provides an article of manufacture comprising a face mask having releasably affixed thereto the present composition, wherein, when the subject wears the face mask, the composition is administered to the subject’s face. This invention will be better understood by reference to the examples which follow, but those skilled in the art will readily appreciate that the specific examples detailed are only illustrative of the invention as described more fully in the claims which follow thereafter. Examples Example 1 – Additional Embodiments of the Present Compositions The following additional combinations of agents are envisioned, without limitation, for the present compositions. Combinations 1 and 2 are for oral use, and combinations 3- 116 are for topical use. Combination 1 comprises gossypol and salycilic acid. Combination 2 comprises hypericin and salycilic acid. Combination 3 comprises hypericin and phloretin. Combination 4 comprises trichostatin A and luteolin. Combination 5 comprises trichostatin A, luteolin, hypericin and phloretin. Combination 6 comprises curcumin, TLR-2 inhibitor, baicalein, and luteolin. Combination 7 comprises phloretin, TLR-2 inhibitor, baicalein, and luteolin. Combination 8 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, baicalein, and luteolin. Combination 9 comprises curcumin, TLR-2 inhibitor, luteolin, and hesperitin. Combination 10 comprises phloretin, TLR-2 inhibitor, luteolin, and hesperitin. Combination 11 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, luteolin, and hesperitin. Combination 12 comprises phloretin, TLR-2 inhibitor, luteolin, and curcumin. Combination 13 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, luteolin, and curcumin. Combination 14 comprises curcumin, TLR-2 inhibitor, baicalein, and salidroside. Combination 15 comprises phloretin, TLR-2 inhibitor, baicalein, and salidroside. Combination 16 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, baicalein, and salidroside. Combination 17 comprises curcumin, TLR-2 inhibitor, hesperitin, and salidroside. Combination 18 comprises phloretin, TLR-2 inhibitor, hesperitin, and salidroside. Combination 19 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, hesperitin, and salidroside. Combination 20 comprises phloretin, TLR-2 inhibitor, curcumin, and salidroside. Combination 21 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, curcumin, and salidroside. Combination 22 comprises curcumin, TLR-2 inhibitor, baicalein, and Aristoyagonine. Combination 23 comprises phloretin, TLR-2 inhibitor, baicalein, and Aristoyagonine. Combination 24 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, baicalein, and Aristoyagonine. Combination 25 comprises curcumin, TLR-2 inhibitor, hesperitin, and Aristoyagonine. Combination 26 comprises phloretin, TLR-2 inhibitor, hesperitin, and Aristoyagonine. Combination 27 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, hesperitin, and Aristoyagonine. Combination 28 comprises phloretin, TLR-2 inhibitor, curcumin, and Aristoyagonine. Combination 29 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, curcumin, and Aristoyagonine. Combination 30 comprises curcumin, TLR-2 inhibitor, baicalein, and Isatis tinctoria. Combination 31 comprises phloretin, TLR-2 inhibitor, baicalein, and Isatis tinctoria. Combination 32 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, baicalein, and Isatis tinctoria. Combination 33 comprises curcumin, TLR-2 inhibitor, hesperitin, and Isatis tinctoria. Combination 34 comprises phloretin, TLR-2 inhibitor, hesperitin, and Isatis tinctoria. Combination 35 comprises Siegesbeckia pubescens Makino, TLR- 2 inhibitor, hesperitin, and Isatis tinctoria. Combination 36 comprises phloretin, TLR-2 inhibitor, curcumin, and Isatis tinctoria. Combination 37 comprises curcumin, Siegesbeckia pubescens Makino, TLR-2 inhibitor, and Isatis tinctoria. Combination 38 comprises curcumin, TLR-2 inhibitor, baicalein, and Withaferin A. Combination 39 comprises phloretin, TLR-2 inhibitor, baicalein, and Withaferin A. Combination 40 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, baicalein, and Withaferin A. Combination 41 comprises curcumin, TLR-2 inhibitor, hesperitin, and Withaferin A. Combination 42 comprises phloretin, TLR-2 inhibitor, hesperitin, and Withaferin A. Combination 43 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, hesperitin, and Withaferin. Combination 44 comprises phloretin, TLR-2 inhibitor, curcumin, and Withaferin A. Combination 45 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, curcumin, and Withaferin A. Combination 46 comprises curcumin, TLR-2 inhibitor, baicalein, and p53 / MDM2 inhibitor. Combination 47 comprises phloretin, TLR-2 inhibitor, baicalein, and p53 / MDM2 inhibitor. Combination 48 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, baicalein, and p53 / MDM2 inhibitor. Combination 49 comprises curcumin, TLR-2 inhibitor, hesperitin, and p53 / MDM2 inhibitor. Combination 50 comprises phloretin, TLR-2 inhibitor, hesperitin, and p53 / MDM2 inhibitor. Combination 51 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, hesperitin, and p53 / MDM2 inhibitor. Combination 52 comprises phloretin, TLR-2 inhibitor, curcumin, and p53 / MDM2 inhibitor. Combination 53 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, curcumin, and p53 / MDM2 inhibitor. Combination 54 comprises trichostatin A, curcumin, TLR-2 inhibitor, baicalein, and luteolin. Combination 55 comprises trichostatin A, phloretin, TLR-2 inhibitor, baicalein, and luteolin. Combination 56 comprises trichostatin A, Siegesbeckia pubescens Makino, TLR-2 inhibitor, baicalein, and luteolin. Combination 57 comprises trichostatin A, curcumin, TLR-2 inhibitor, luteolin, and hesperitin. Combination 58 comprises trichostatin A, phloretin, TLR-2 inhibitor, luteolin, and hesperitin. Combination 59 comprises trichostatin A, Siegesbeckia pubescens Makino, TLR-2 inhibitor, luteolin, and hesperitin. Combination 60 comprises trichostatin A, curcumin, phloretin, TLR-2 inhibitor, and luteolin. Combination 61 comprises trichostatin A, curcumin, Siegesbeckia pubescens Makino, TLR-2 inhibitor, and luteolin. Combination 62 comprises curcumin, TLR-2 inhibitor, baicalein, Isatis tinctoria, and p53 / MDM2 inhibitor. Combination 63 comprises phloretin, TLR-2 inhibitor, baicalein, Isatis tinctoria, and p53 / MDM2 inhibitor. Combination 64 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, baicalein, Isatis tinctoria, and p53 / MDM2 inhibitor. Combination 65 comprises curcumin, TLR-2 inhibitor, hesperitin, Isatis tinctoria, and p53 / MDM2 inhibitor. Combination 66 comprises phloretin, TLR-2 inhibitor, hesperitin, Isatis tinctoria, and p53 / MDM2 inhibitor. Combination 67 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, hesperitin, Isatis tinctoria, and p53 / MDM2 inhibitor. Combination 68 comprises phloretin, TLR-2 inhibitor, curcumin, Isatis tinctoria, and p53 / MDM2 inhibitor. Combination 69 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, curcumin, Isatis tinctoria, and p53 / MDM2 inhibitor. Combination 70 comprises curcumin, TLR-2 inhibitor, baicalein, Withaferin A, and luteolin. Combination 71 comprises phloretin, TLR-2 inhibitor, baicalein, Withaferin A, and luteolin. Combination 72 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, baicalein, Withaferin A, and luteolin. Combination 73 comprises curcumin, TLR-2 inhibitor, hesperitin, Withaferin A, and luteolin. Combination 74 comprises phloretin, TLR-2 inhibitor, hesperitin, Withaferin A, and luteolin. Combination 75 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, hesperitin, Withaferin A, and luteolin. Combination 76 comprises phloretin, TLR-2 inhibitor, curcumin, Withaferin A, and luteolin. Combination 77 comprises curcumin, TLR-2 inhibitor, baicalein, Isatis tinctoria, and luteolin. Combination 78 comprises phloretin, TLR-2 inhibitor, baicalein, Isatis tinctoria, and luteolin. Combination 79 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, baicalein, Isatis tinctoria, and luteolin. Combination 80 comprises curcumin, TLR-2 inhibitor, hesperitin, Isatis tinctoria, and luteolin. Combination 81 comprises phloretin, TLR-2 inhibitor, hesperitin, Isatis tinctoria, and luteolin. Combination 82 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, hesperitin, Isatis tinctoria, and luteolin. Combination 83 comprises phloretin, TLR-2 inhibitor, curcumin, Isatis tinctoria, and luteolin. Combination 84 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, curcumin, Isatis tinctoria, and luteolin. Combination 85 comprises curcumin, TLR-2 inhibitor, baicalein, Withaferin A, and salidroside. Combination 86 comprises phloretin, TLR-2 inhibitor, baicalein, Withaferin A, and salidroside. Combination 87 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, baicalein, Withaferin A, and salidroside. Combination 88 comprises curcumin, TLR-2 inhibitor, hesperitin, Withaferin A, and salidroside. Combination 89 comprises phloretin, TLR-2 inhibitor, hesperitin, Withaferin A, and salidroside. Combination 90 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, hesperitin, Withaferin A, and salidroside. Combination 91 comprises phloretin, TLR-2 inhibitor, curcumin, Withaferin A, and salidroside. Combination 92 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, curcumin, Withaferin A, and salidroside. Combination 93 comprises curcumin, TLR-2 inhibitor, baicalein, Isatis tinctoria, and salidroside. Combination 94 comprises phloretin, TLR-2 inhibitor, baicalein, Isatis tinctoria, and salidroside. Combination 95 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, baicalein, Isatis tinctoria, and salidroside. Combination 96 comprises curcumin, TLR-2 inhibitor, hesperitin, Isatis tinctoria, and salidroside. Combination 97 comprises phloretin, TLR-2 inhibitor, hesperitin, Isatis tinctoria, and salidroside. Combination 98 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, hesperitin, Isatis tinctoria, and salidroside. Combination 99 comprises phloretin, TLR-2 inhibitor, curcumin, Isatis tinctoria, and salidroside. Combination 100 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, curcumin, Isatis tinctoria, and salidroside. Combination 101 comprises curcumin, TLR-2 inhibitor, baicalein, Withaferin A, and Aristoyagonine. Combination 102 comprises phloretin, TLR-2 inhibitor, baicalein, Withaferin A, and Aristoyagonine. Combination 103 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, baicalein, Withaferin A, and Aristoyagonine. Combination 104 comprises curcumin, TLR-2 inhibitor, hesperitin, Withaferin A, and Aristoyagonine. Combination 105 comprises phloretin, TLR-2 inhibitor, hesperitin, Withaferin A, and Aristoyagonine. Combination 106 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, hesperitin, Withaferin A, and Aristoyagonine. Combination 107 comprises phloretin, TLR-2 inhibitor, curcumin, Withaferin A, and Aristoyagonine. Combination 108 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, curcumin, Withaferin A, and Aristoyagonine. Combination 109 comprises curcumin, TLR-2 inhibitor, baicalein, Isatis tinctoria, and Aristoyagonine. Combination 110 comprises phloretin, TLR-2 inhibitor, baicalein, Isatis tinctoria, and Aristoyagonine. Combination 111 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, baicalein, Isatis tinctoria, and Aristoyagonine. Combination 112 comprises curcumin, TLR-2 inhibitor, hesperitin, Isatis tinctoria, and Aristoyagonine. Combination 113 comprises phloretin, TLR-2 inhibitor, hesperitin, Isatis tinctoria, and Aristoyagonine. Combination 114 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, hesperitin, Isatis tinctoria, and Aristoyagonine. Combination 115 comprises phloretin, TLR-2 inhibitor, curcumin, Isatis tinctoria, and Aristoyagonine. Combination 116 comprises Siegesbeckia pubescens Makino, TLR-2 inhibitor, curcumin, Isatis tinctoria, and Aristoyagonine. Example 2 – Measuring Epigenetic Dysregulation The success of the present composition in ameliorating epigenetic dysregulation in a subject (e.g., a human subject) can be measured, for example, by making any of the following determinations: (i) the subject’s epigenetic methylation, histonylation, and / or chromatin patterns more closely resemble the patterns of younger persons (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); (ii) an epigenetic clock (e.g., a Horvath clock or a Levine clock)-measuring methylation of DNA in different regions of the subject’s DNA more closely resembles the DNA methylation pattern of a younger subject (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); (iii) an epigenetic DNA methylation clock (e.g., a Horvath clock or a Levine clock) shows that an adult human subject has been rejuvenated by at least 3 months, one year, at least two years, or at least three years after being administered the present composition (or of which the epigenetic age or biological age has been decreased by at least 1%, at least 2%, at least 3%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% compared to a subject’s chronological age); (iv) the subject’s chromatin distribution more closely resembles that of a younger subject (e.g., by at least 0.2%, at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); (v) the subject’s transcriptome resembles the transcriptome of a younger subject (e.g., by at least 0.2%, at least 0.5%, at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); (vi) the subject’s expression profile of ribosome-related proteins and / or ribosome-related RNA more closely resembles that of a younger organism (e.g., by at least 0.2%, at least 0.5%, at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); or (vii) the subject’s levels of sirtuins have increased (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%). The success of the present composition in ameliorating epigenetic dysregulation in a subject (e.g., a human subject) can also be measured, for example, by making any of the following determinations: (i) an increase in the level of H3K9me3 in the subject (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); or (ii) an increase in the level of heterochromatin protein (Hp1y) in the subject (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%). The success of the present composition in ameliorating epigenetic alterations in a subject (e.g., a human subject) can be measured, for example, by making any of the following determinations: (i) a reduction in specific DNA methylation changes, such as hypermethylation of the ELOVL2 gene, which have been correlated with chronological age and are linked to both intrinsic and extrinsic skin aging (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); or (ii) an improvement in epigenetic clocks such as the "skin-blood clock," which are predictive tools based on DNA methylation data and are used to measure age acceleration in skin cells, correlating strongly with chronological age and health outcomes (e.g., by at least 1 year, at least 2 years, at least 3 years, or at least 5 years). The success of the present composition can also be measured by (i) a reduction in histone modifications associated with aging, such as increased acetylation of histone H4K16, which affects gene expression and contributes to age-associated phenotypic changes (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); or (ii) increases significantly after UV exposure and reflects DNA damage and aging, detectable via immunohistochemistry in skin biopsy samples (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%). Further success of the present composition can be determined by (i) improvements in other epigenetic clocks such as DunedinPACE and GrimAge, which are used to predict biological age and estimate the pace of aging through DNA methylation patterns in skin cells (e.g., by at least 1 year, at least 2 years, at least 3 years, or at least 5 years); or (ii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in age-associated DNA methylation markers across skin cells, including loci tied to the regulation of skin health and regeneration, that are predictive of epigenetic age acceleration. Finally, the success of the present composition can be determined by (i) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in histone modifications associated with epigenetic regulation of inflammatory responses, such as H3K27me3, which has been linked to transcriptional repression and aging; or (ii) improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in epigenetic biomarkers related to stress responses, to interventions. Example 3 – Measuring Cell Senescence The success of the present composition in ameliorating cell senescence in a subject (e.g., a human subject) can be measured, for example, by making any of the following determinations: (i) a delay in the occurrence of senescent cells or a delay in the transition of normal cells into senescent cells in vitro or in vivo (e.g., by at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); and / or (ii) a decrease in the number of senescent cells in vitro or in vivo (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%). Senescence or senescent-like status of cells can be measured, for example, via one or more of the following: (i) epigenetic profiling such as measuring epigenetic markers of senescence (e.g., changes in histone H3 lysine 9 and 27 trimethylation (changed levels of H3K9me3 and H3K27me3), changed heterochromatin protein 1 (HP1) family protein levels, increased histone variant macroH2A levels, and / or chromatin remodeling enzyme ATRX levels); (ii) changes in cell morphology resembling the morphology of senescent cells, (e.g., enlarged size, a more flattened shape, polyploid nuclei, or accumulation of DNA damage foci); (iii) changes in levels of nuclear lamina-associated proteins such as lamins (e.g., a decline lamin B1); (iv) heterochromatin changes more resembling the heterochromatin status of senescent cells (e.g., an increase in senescence-associated heterochromatic foci (SAHF)); (v) an increase of senescence-associated distention of satellites (SADS) or other changes in pericentric satellite DNA more resembling that of senescent cells; or (vi) changes in secretory phenotype corresponding to that of senescent cells (e.g., the occurrence of a more senescence-associated secretome including, without limitation, cytokines, interleukins (e.g., IL-1, IL-2, IL-6, Il-8, and TNF- alpha), matrix metalloproteinases, pro angiogenetic factors, pro-inflammatory substances, and growth factors (e.g., vascular endothelial growth factor, insulin like growth factor, and GM-CSF)). The success of the present composition in ameliorating cell senescence in a subject (e.g., a human subject) can also be measured, for example, by making any of the following determinations: (i) an increase in the level of H3K9me3 in the subject (e.g., by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); (ii) an increase in the level of H3K27me3 in the subject (e.g., by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); (iii) a decrease in the level of P16INK4A in the subject (e.g., by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); or (iv) a decrease in the level of one or more of p16, p53, p21, p14, p15, and beta-galactosidase activity in the subject (e.g., by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%). Example 4 – Measuring Altered Intercellular Communication The success of the present composition in ameliorating altered intercellular communication in a subject (e.g., a human subject) can be measured, for example, by making any of the following determinations: (i) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in inflammatory cytokinesand chemokines such as IL- -18, CXCL1, CXCL8 (IL-8), CXCL9, CXCL10,CXCL12, CXCL16, and CCL11 (eotaxin), which are involved in inflammatory signaling within the skin; (ii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the levels of senescence-associated secretory phenotype (SASP) factors, which contribute to a pro-inflammatory environment in aged skin; or (iii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the levels of acute-phase proteins and other inflammatory mediators, such as serum amyloid A (SAA), Annexin A1, and COX-2, which play a role in age-related inflammatory processes. The success of the present composition can also be measured by determining (i) an improvement in signal transduction pathways, including reductions (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in components such as Aryl Hydrocarbon Receptor (AHR), Caveolin-1, Caveolin-2, and Fibroblast Growth Factor 7 (FGF7), which are essential for proper cell signaling in the skin; or (ii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in other signal transduction pathways components such as Neuregulin-1 (NRG1), Ephrin Receptors (EphRs), and Wnt signaling pathway components, indicating improved cellular communication. Further success can be determined by measuring changes in extracellular matrix (ECM) integrity and remodeling, as indicated by (i) increases (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the levels of collagen-related proteins such as Collagen IV, Collagen XVII (BP180), Procollagen Type I N-Terminal Propeptide (PINP), Procollagen Type III N-Terminal Propeptide (PIIINP), and enzymes like LOX (and its family members Loxl1, Loxl2, Loxl3, and Loxl4), all of which are involved in maintaining skin structure; or (ii) improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in ECM glycoproteins and proteoglycans such as Fibronectin, Fibrillin-1, Fibulin-5, Laminin, Perlecan, Versican, Syndecan-1, Decorin, and Glypican- 1, indicating a restoration of ECM integrity. The success of the present composition can further be measured by determining improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in cell-cell adhesion and junctional proteins, including Cadherins (e.g., E-cadherin, N-Cadherin), Catenins (e.g., Beta-catenin), Desmosomal components maintaining skin cellular adhesion and integrity. The composition’s success can also be measured by determining reductions (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in oxidative stress markers such as A2M (Alpha-2-Macroglobulin) and improvements in heat shock proteins like HSP70, HSP90, and Thioredoxin, which play key roles in cellular stress responses. Finally, the success of the present composition can be evaluated by determining (i) reductions (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in dysfunction mediated by exosomes and extracellular vesicles (EVs), indicating restored intercellular communication, and (ii) improved vascular integrity (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) as measured by angiogenic markers such as VEGF, Angiogenin, and Endoglin (CD105), or vascular integrity proteins such as Caveolin-1, Caveolin-2, and ET-1. Example 5 – Measuring Autophagy The success of the present composition in ameliorating decreased autophagy in a subject (e.g., a human subject) can be measured, for example, by determining any of the following: (i) an increase in the level of one or more of LC3, p62, Ulk1, Parkin, PINK1, LAMP2A, Atg, FIP200, Vps15, Beclin, Lamp-1, Lamp-2, Hsp70, Hsp90, and SQSTM1 in the subject (e.g., by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); (ii) an increase (e.g., by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in any of phagophore formation, autophagosome formation, lysosome numbers, lysosomal activity, LC3 puncta, lysosomal content (as determined, for example, using immunochemistry, electron microscopy, Western blotting, or flow cytometry); (iii) increased lysosome acidity (e.g., by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); (iv) upregulation of the ubiquitin-proteasome system (e.g., by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); or (v) inhibition of mTOR or the mTOR pathway (e.g., by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%). Example 6 – Measuring Cell Oxidation The success of the present composition in ameliorating cell oxidation in a subject (e.g., a human subject) can be measured, for example, by making any of the following determinations: (i) a decrease in the level of 8-isoprostane in the subject (e.g., by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); (ii) a decrease in the level of 8-hydroxydeoxyguanosine (8-OHdG) in the subject (e.g., by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); or (iii) a decrease in the subject of levels of any of oxidized LDL, malondialdehyde (MDA), 4-HNA, lipid hydroperoxides, oxidized proteins, protein carbonylation and protein nitration (3-nitrotyrosines), advanced glycation end products (AGEs), and advanced oxidation protein products (e.g., by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%). Example 7 – Measuring Telomere Fitness The success of the present composition in ameliorating telomere shortening in a subject (e.g., a human subject) can be measured, for example, by making any of the following determinations: (i) an increase (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in telomere length as measured by quantitative fluorescence in situ hybridization (Q-FISH), which uses telomeric probes to measure fluorescence intensity directly in tissue sections, correlating well with traditional methods; (ii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in telomere shortening as measured by the Telomere Restriction Fragment (TRF) assay, which is considered the gold standard for measuring telomere length via Southern blotting, providing an accurate assessment of telomere health; or (iii) an increase in mRNA expression of telomerase, TERT, TERC, or telomerase-related genes (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%). The success of the present composition can also be measured by determining (i) an improvement (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in telomere length as assessed by quantitative PCR (qPCR), which is a widely used method that is cost-effective and suitable for large epidemiological studies; or (ii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in telomere dysfunction as measured by fluorescence in situ hybridization (FISH) combined with immunohistochemistry, allowing for cell-type-specific analysis in skin cells like fibroblasts. Further success of the present composition can be determined by measuring (i) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in proteins induced by telomere dysfunction, such as CRAMP, stathmin,and EF- -dysfunctional cells and increase with age,correlating with chronic diseases; or (ii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in telomere dysfunction- induced foci (TIF), markers that signal senescence in telomere-dysfunctional cells. The success of the present composition can also be measured by determining (i) an improvement (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in circulating telomerase activity, which can be detected in blood and tissue samples and is a useful indicator of both systemic and localized aging processes, particularly in skin aging and disease; or (ii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in critically short telomeres (CSTs) measured using high-throughput cytometry, providing an accurate picture of telomere health and aging. Finally, the success of the present composition can be assessed by measuring (i) improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in individual telomere length using the single-molecule telomere length assay, which measures individual telomere lengths and identifies critically short telomeres in aging and age-related diseases; or (ii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in chromosomes with critically short telomeres, as measured using high-throughput cytometry, to reflect improvements in telomere stability. Example 8 – Measuring Stem Cell Fitness The success of the present composition in ameliorating stem cell exhaustion in a subject (e.g., a human subject) can be measured, for example, by determining an increase in the number of stem cells in vivo (e.g., by at least 1%, at least 2%, at least 5%). This increase can be measured in vitro or in vivo via, for example, one or more of the following biomarkers (i) muscle satellite stem cell biomarkers (e.g., PAX7, LMNA, and emerin); (ii) neuronal stem cell biomarkers (e.g., Nestin, Sox2, ASCL1 / Mash1, ABCG2, BMI-1, beta-Catenin, Brg1, N-Cadherin, Calcitonin R, CD15 / Lewis X, CD133, CDCP1, COUP-TF I / NR2F1, CXCR4, FABP7 / B-FABP, FABP8 / M-FABP, FGFR2, FGFR4, FoxD3, Frizzled-9, GCNF / NR6A1, GFAP, Glut1, HOXB1, ID2, LRTM1, Meteorin, MSX1, Musashi-1, Musashi-2, Nestin, NeuroD1, Noggin, Notch-1, Notch-2, Nrf2, Nucleostemin, Numb, Otx2, Pax3, Pax6, PDGF R alpha, PKC zeta, Prominin 2, ROR2, RUNX1 / CBFA2, RXR alpha / NR2B1 sFRP-2, SLAIN1, SOX1, SOX2, SOX9, SOX11, SOX21, SSEA-1, SSEA-4, TRAF-4, Vimentin, and ZIC1); (iii) pluripotency stem cell markers (e.g., Oct4, NANOG, Sox2, and Myc); (iv) hematopoietic stem cell markers (e.g., CD34, CD59, and CD90 / Thy1); or (v) mesenchymal stem cell markers (e.g., CD105, CD90, CD73, CD44, CD45, CD29, CD166, Stro-1, CD106, and GSTT1). Since measuring stem cells in vivo is difficult and costly, success of the present composition in ameliorating stem cell exhaustion can also be measured, for example, by making the following preferred in vitro (“lab dish”) determinations (as well as in vivo determinations): (i) an increase in the number of stem cells (e.g., by at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); (ii) increased viability of the stem cells (e.g., by at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); (iii) an increase in potency of the stem cells in vitro (and in vivo as well) (e.g., by at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); (iv) an increase in the quality of stem cells, measured for example by an increase in growth of the stem cells, an increase in the ability to proliferate, an increase in the ability to form colonies, or an increase in the ability to produce cells (e.g., by at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); (v) an increased lifespan of stem cells, as measured in hours (e.g., by at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); or (vi) an increased resistance of stem cells against cellular stressors (e.g., heat, cold, or toxins) (e.g., by at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%). The success of the present composition in ameliorating stem cell exhaustion in a subject (e.g., a human subject) can further be measured, for example, by making any of the following determinations in vitro, but also in vivo: (i) improved stem cell function (e.g., by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) as measured, for example, by replication ability, potency, proliferation capability, survival (as measured, for example, temporally (e.g., number of extra hours of survival), by exposing stem cells to physiological stressors and toxins), potency, and quality (e.g., stem cells have an increased number of replications or can generate / produce larger numbers of cells stemming from the stem cells or display increase cell division markers (e.g., cyclin D1 or increased B-catechin); (ii) improved stem cell transcriptome (i.e., the stem cell’s transcriptome is more similar to the transcriptome of a younger stem cell or a more functional stem cell) (e.g., by at least 0.5%, at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); (iii) improved stem cell proteome (i.e., the stem cell’s proteome is more similar to the proteome of a younger stem cell or more functional stem cell) (e.g., by at least 0.5%, at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); or (iv) an improved stem cell epigenome (i.e., the stem cell’s epigenome is more similar to the epigenome of a younger stem cell or more functional stem cell) (e.g., by at least 0.5%, at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%), as assessed, for example, by measuring methylation or histonylation patterns and comparing them to those of younger, more functional, or more potent stem cells. Example 9 – Measuring Physiological Biomarkers as Indicators of Stem Cell Fitness and Senescent Cell Levels in an Organism The success of the present composition in ameliorating adverse physiological events in a subject (e.g., a human subject) can be measured, for example, by making any of the following determinations: (i) a decrease in the number and / or severity of skin wrinkles as measured, for example, via wrinkle surface area (e.g., via 3D topography or profilometry); (ii) an increase in skin radiance as measured, for example, via an identometer, cutometer, transepidermal water loss meter, corneometer, or a skin transcriptome or proteome biomarker panel that shows improved skin functioning; (iii) improved cognition as measured, for example, via a cognitive test; (iv) improved feelings of happiness as measured, for example, via the Depressive Symptoms Scale; (v) reduced frailty, as measured, for example, via an international frailty scale or mobility scale (such as the Canadian Study on Health & Aging Clinical Frailty Scale (CSHA-CFS)); (vi) improved reaction time; (vii) improved neuromuscular capability and strength (e.g., increased stamina, improved balance, improved proprioception, improved mobility (measured by 6-minute walk test (6MWT), 4-m gait speed test (4MGST), improved short physical performance battery (SPPB) score, or tests measuring balance, gait speed tests, chair stand tests or other markers of physical function), increased grip strength, increased power, increased activity levels, improved 400 m walk test, and improved arm curl test results); (viii) improved blood flow, as measured by increase of unit of blood per mm3of tissue; (ix) reduced blood pressure; (x) improved vascular health, as measured, for example, via pulse wave velocity of the blood vessels or flow-mediated vasodilatation; (xi) induced weight loss, a reduction in waist circumference or BMI, or a reduction in abdominal fat volume; (xii) improvement in heart rate variability (HRV); and (xiii) improvement in an AI-assessed facial aging profile (e.g., as measured via facial AI software that for example assesses wrinkle area, blood flow, or skin sagging). Importantly, if stem cell health is improved and cell senescence is reduced, the various physiological biomarkers discussed in this example will also improve. This is particularly the case with stem cells in that reducing the aging hallmark of stem cell decline (the measurement of which is discussed above) improves physiological biomarkers. Example 10 – Measuring Genomic Instability The success of the present composition in ameliorating genomic instability in a subject (e.g., a human subject) can be measured, for example, by making any of the following determinations: (i) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) -H2AX, which detects double-strand DNA breaks and can be used in skin biopsies to assess damage from UV exposure or aging; or (ii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in mitochondrial DNA (mtDNA) mutations, particularly the 4977 bp deletion in mtDNA, which is detectable in hair follicles and associated with aging and genomic instability. The success of the present composition can also be measured by determining (i) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in microsatellite instability (MSI), which is indicative of chromosomal instability and detectable in skin biopsies using in situ hybridization techniques; or (ii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in micronuclei formation, which is a biomarker for chromosomal instability and DNA damage, typically detected in DNA damage assays. Further success of the present composition can be determined by determining (i) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in DNA damage as measured by the micronucleus (MN) assay, which detects chromosomal instability and micronuclei formation in skin cells; or (ii) improvements in nuclear morphometry, using computer-assisted analysis to measure changes in nuclear size and shape (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%), which reflect DNA instability in skin biopsies. The success of the present composition can also be measured by determining (i) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in chromosomal aberrations, which are markers of chromosomal instability detected through in situ hybridization techniques, particularly in skin tissues; or (ii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the mitochondrial DNA deletion spectrum, using long PCR techniques to identify mtDNA deletions, which are biomarkers of UV radiation exposure and aging in the epidermis. Further success can be determined by measuring (i) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the mitochondrial DNA 3895-bp deletion, a biomarker of sunlight exposure in human skin, detectable using real-time PCR techniques; or (ii) improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in structural skin integrity as detected through imaging-based biomarkers such as reflectance confocal microscopy (RCM), which is a non-invasive imaging technique that visualizes signs of aging and genomic instability by detecting structural changes in the skin. Finally, the success of the present composition can be assessed by measuring improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in ultrasonic imaging, which can evaluate skin thickness and dermal changes due to aging, serving as a marker for structural genomic instability. Example 11 – Measuring Improvement in Deregulated Nutrient Sensing The success of the present composition in ameliorating deregulated nutrient sensing in a subject (e.g., a human subject) can be measured, for example, by making any of the following determinations: (i) an increase in the level of insulin sensitivity in the subject (e.g., by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); or (ii) a decrease in the level of fasting glucose, fasting insulin, LDL, HbA1c, mTOR activity, or mitochondrial reactive oxygen species in the subject (e.g., by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%). Example 12 – Measuring Microbiome Dysbiosis The success of the present composition in ameliorating microbiome dysbiosis in a subject (e.g., a human subject) can be measured, for example, by making any of the following determinations: (i) the subject’s skin microbiome diversity more closely resembles the microbial diversity of younger individuals (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); (ii) the presence of beneficial microbial species, such as Faecalibacterium prausnitzii, has increased (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); (iii) the levels of short-chain fatty acids (SCFAs), such as butyrate, have increased (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%), reflecting restored microbial function with positive systemic effects on skin health; or (iv) the subject’s gut-skin axis is rejuvenated (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%), indicated by improved microbial diversity and the restoration of age-related changes in skin health biomarkers. The success of the present composition in ameliorating microbiome dysbiosis can also be measured by making the following determinations: (i) an improvement in the subject’s skin biological age as measured by microbiome-related aging clocks (e.g., by at least 3 months, at least one year, at least two years, or at least three years); or (ii) an increase (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in beneficial gut metabolites, such as butyrate, correlating with a reduction in skin inflammation and improvements in skin barrier function. Example 13 – Measuring Chronic Inflammation The success of the present composition in ameliorating chronic inflammation (inflammaging) in a subject (e.g., a human subject) can be measured, for example, by making any of the following determinations: (i) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in skin-specific inflammatory biomarkers, such as S100 proteins (e.g., S100A8 / A9), which are associated with inflammatory responses in the skin; (ii) a decrease (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the levels of active caspase-1 (ACasp-1), an indicator of inflammasome activation in skin cells such as keratinocytes; or (iii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in systemic markers of chronic inflammation, such as tumor necrosis factor-alpha (TNF- receptor (suPAR), or circulating cell-free DNA (cfDNA), all of which contribute to skin aging. The success of the present composition in reducing chronic inflammation can also be determined by (i) measuring the reduction of pro-inflammatory cytokines secreted by senescent cells (e.g., IL-6, IL-8, and IL- least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); or (ii) assessing changes in microRNAs (miRNAs), particularly inflamma-miRs such as miR-21 and miR- 146a, which are linked to inflammation and are found in both serum and skin. A decrease (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the expression levels of these miRNAs would indicate a reduction in chronic inflammation. The success of the present composition in reducing chronic inflammation can also be determined by (i) assessing the decrease (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in histological signs of inflammation in skin biopsy samples, such as a reduction in the infiltration of inflammatory cells (e.g., T cells and macrophages) into the dermis; or (ii) monitoring improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in skin architecture using non-invasive imaging techniques, such as Optical Coherence Tomography (OCT) or Reflectance Confocal Microscopy (RCM), which detect changes in epidermal thickness or inflammatory cell infiltration. The success of the present composition can further be indicated by a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in inflammatory biomarkers collected through skin biopsy samples or skin imaging, including a decrease in inflamma-miRs such as miR-21 and miR-146a. Example 14 – Measuring Stem Cell Exhaustion The success of the present composition in ameliorating stem cell exhaustion in a subject (e.g., a human subject) can be measured, for example, by making any of the following determinations: (i) an increase (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the number of Keratin 19 (K19) positive cells, which are often associated with stem cell populations in the skin; (ii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the accumulation of 53BP1-foci, which are indicative of DNA damage and correlate with aging and stem cell exhaustion in the skin; or (iii) an improvement (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in glycan profiles, specifically a reduction in the age-related increase in sialylation and alterations in mannose-binding that affect stem cell regenerative capacity. The success of the present composition can also be measured by (i) an increase (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the density of miR-125b-positive epidermal stem cells, which decreases with age; (ii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in alterations in the Jak-Stat signaling pathway, which are linked to decreased function and an increased number of stem cells during aging; or (iii) a restoration (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) of RNA splicing patterns, particularly in splice isoforms of stem cell- related genes, which are altered in aging stem cells. The success of the present composition can further be measured by (i) an improvement (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the regenerative ability of stem cells, as indicated by an increased response to defensin peptides, which are released by neutrophils during wounding and activate specific stem cells to create new cells; or (ii) an increase (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the expression of dermal stem / progenitor cell biomarkers such as SOX2, NANOG, and S100B, which decline with photoaging and UVA irradiation. Finally, the success of the present composition can be measured by the reactivation (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) of embryonic and stemness genes, such as NANOG and LIN28, in aged skin cells, indicating an increase in the capacity for tissue repair and regeneration. Example 15 – Measuring Cellular Senescence The success of the present composition in ameliorating cellular senescence in a subject (e.g., a human subject) can be measured, for example, by making any of the following determinations: (i) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in senescence-associated enzymes such asSenescence-Associated Beta-Galactosidase (SA- -gal), which is commonly used fordetecting senescent cells via histochemical staining; (ii) a decrease (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) - fucosidase, a novel enzymatic biomarker for senescence detection in multiple models; (iii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in reactive oxygen species (ROS), which are by-products of oxidative metabolism and increase in senescent cells; or (iv) a decrease (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in serine protease inhibitors (SERPINs), which regulate proteolysis and are associated with senescence. The success of the present composition can also be measured by (i) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in cell cycle inhibitors such as p16INK4a and p21, which increase with age and can be measured in skin biopsy samples; or (ii) a decrease (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in p53, a tumor suppressor protein involved in regulating cell cycle arrest during senescence. Further success can be determined by measuring changes in DNA damage and repair markers, such as (i) reductions (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) -strand DNA breaks; (ii) decreases (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in 53BP1, a DNA damage response protein that localizes to double-strand breaks; or (iii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in senescence-associated DNA damage foci (DNA-SCARS), which are hallmark structures of senescent cells. The success of the present composition can further be measured by (i) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in nuclear and chromatin changes such as the loss of Lamin B1, a marker of nuclear lamina alterations and senescence; (ii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in Senescence- Associated Heterochromatin Foci (SAHF), which are regions of condensed chromatin in senescent cells; or (iii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in High Mobility Group Box 1 (HMGB1), a nuclear protein that relocates to the extracellular space during senescence. The success of the present composition can also be measured by (i) reductions (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in markers related to apoptosis resistance and senescence differentiation, such as Annexin V, used to distinguish apoptosis from senescence; or (ii) a decrease (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in cleaved caspases and PARP, which are indicators of apoptosis resistance in senescent cells. Further success can be measured by reductions (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in secretory phenotype (SASP) components such as fibronectin, an ECM protein secreted by senescent cells that contributes to tissue remodeling. Finally, the success of the present composition can be determined by (i) reductions (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in senescence-associated structural and metabolic changes, including a decrease in lipofuscin, an age-related pigment that accumulates in senescent cells; (ii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in senescence-associated lipid droplets, lipid accumulations linked to metabolic dysfunction in senescent cells; (iii) improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in mitochondrial dysfunction, as indicated by mitochondrial membrane potential and ROS production in senescent cells; (iv) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in altered autophagy processes, as measured by autophagy markers LC3 and p62; or (v) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in novel and emerging senescence biomarkers, such as Pregnancy Zone Protein (PZP) and Senescence- Associated Distension of Satellites (SADS), which indicate altered chromatin structure in senescent cells. Example 16 – Measuring Mitochondrial Dysfunction The success of the present composition in ameliorating mitochondrial dysfunction in a subject (e.g., a human subject) can be measured, for example, by making any of the following determinations: (i) an increase (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in mitochondrial DNA (mtDNA) content, which typically declines with age; (ii) an improvement (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in mitochondrial membrane potential (MMP), using fluorescence-based dyes like JC-1, indicating restored mitochondrial function; or (iii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in mitochondrial fragmentation detected through imaging techniques, reflecting improvements in mitochondrial structure. The success of the present composition can also be measured by (i) improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in NADH fluorescence imaging (using two-photon excited fluorescence), which indicates restored mitochondrial redox status and energy metabolism; or (ii) an increase (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in mitochondrial fusion and fission protein expression, such as Mitofusins (MFN1 / 2) and Dynamin-related protein 1 (DRP1), which regulate mitochondrial dynamics. Further success of the present composition can be determined by (i) an increase (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in autophagy markers such as LC3-II and p62, which are involved in the degradation and recycling of damaged mitochondria; (ii) improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in cytochrome c oxidase (COX) activity, measured in skin biopsies to assess the respiratory function of mitochondria; or (iii) a significant increase (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in mitochondrial ATP production levels, reflecting restored mitochondrial energy production. The success of the present composition can further be measured by determining (i) reductions (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in oxidative stress markers such as 8-hydroxy-2'-deoxyguanosine (8- OHdG), which are indicative of oxidative damage to mitochondrial DNA; or (ii) improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in mitochondrial morphology, assessed by electron microscopy to evaluate mitochondrial structure and fragmentation. Further success can be assessed by detecting mitochondrial DNA (mtDNA) mutations or deletions, such as the 4977 bp deletion in circulating blood cells, which are associated with aging. Finally, the success of the present composition can be determined by measuring (i) improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in serum growth differentiation factor 15 (GDF15), which reflects mitochondrial health and cellular stress responses; or (ii) an increase (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in lipophilic antioxidants such as coenzyme Q10 and vitamin E, which protect mitochondrial function and reduce oxidative stress. Example 17 – Measuring Deregulated Nutrient-Sensing The success of the present composition in ameliorating deregulated nutrient-sensing in a subject (e.g., a human subject) can be measured, for example, by making any of the following determinations: (i) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) - H2AX, which reflect cellular stress in aging skin; or (ii) an increase (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the levels of sirtuins, such as SIRT1 and SIRT6, which are proteins involved in regulating cellular metabolism, DNA repair, and aging processes. The success of the present composition can also be measured by (i) increases (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in involved in dermal fibroblast aging and extracellular matrix remodeling; or (ii) an increase (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in Fibroblast Growth Factor 21 (FGF-21), a metabolic regulator that plays a role in nutrient-sensing pathways and aging. Further success of the present composition can be determined by (i) an improvement (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the levels of Insulin-like Growth Factor Receptor (IGF-1R), which is linked to nutrient-sensing pathways and skin aging; or (ii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in collagen glycation and glycoxidation products, such as Pentosidine and Carboxymethyllysine (CML), which indicate modifications to collagen due to glucose metabolism and skin aging. The success of the present composition can also be measured by (i) an improvement (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the expression of Tubulin Beta-3 Chain, a protein that has been identified as a marker for skin aging; or (ii) an increase (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in ceramides and lipid metabolism markers, which are key indicators of skin barrier function and changes in lipid metabolism associated with aging. Further success of the present composition can be determined by (i) an improvement (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in skin intrinsic fluorescence (SIF), a non-invasive imaging technique that assesses skin aging through autofluorescence of metabolic byproducts; or (ii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the accumulation of advanced glycation end products (AGEs), which contribute to chronic inflammation and oxidative stress, both of which are linked to skin aging. Additionally, the success of the present composition can be measured by (i) changes in the bioelectrical properties of the skin during aging, especially as assessed through bioimpedance spectroscopy (BIS) (e.g., a decrease in resistance and time constant of at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) and an increase in phase angle (e.g., of at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); or (ii) improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in epigenetic clocks, including DNA methylation patterns that estimate biological age, which can be reversed through improvements in nutrient-sensing pathways. Additionally, the success of the present composition can be assessed by (i) an improvement (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the levels of metabolic and endocrine biomarkers such as Insulin-like Growth Factor 1 (IGF-1), which is a systemic regulator of growth and nutrient-sensing linked to aging-related skin changes; or (ii) improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in adipokines such as Leptin and Adiponectin, which are involved in fat metabolism and indirectly affect skin aging by influencing collagen and elasticity. The success of the present composition can further be measured by (i) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in glycated hemoglobin (HbA1c), which is a marker of glucose metabolism dysregulation contributing to glycation of skin proteins; or (ii) a decrease (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in circulating microRNAs, such as miR-302b-3p, which are involved in nutrient-sensing and skin fibroblast senescence. Finally, the success of the present composition can be determined by a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in mitochondrial DNA (mtDNA) damage, which is an indicator of nutrient-sensing dysfunction in aged skin. Example 18 – Measuring Disabled Macroautophagy The success of the present composition in ameliorating disabled macroautophagy in a subject (e.g., a human subject) can be measured, for example, by making any of the following determinations: (i) a change (e.g., an increase of at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the LC3-II / I ratio, which reflects autophagosome formation; a decrease in this ratio suggests impaired autophagy; or (ii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the accumulation of p62 / SQSTM1, which accumulates when autophagy is impaired and indicates disrupted autophagic flux. The success of the present composition can also be measured by (i) improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the expression of autophagy-related genes such as ATG7 and ATG5, whose reduced expression is linked to aging and autophagy impairment in skin; or (ii) an increase (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in Beclin-1, which is involved in the initiation of autophagy and whose decline contributes to aging-related phenotypes. Further success can be determined by (i) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in oxidative stress markers such as 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker for oxidative stress and mitochondrial DNA damage, which is linked to impaired autophagy; or (ii) improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the levels of fibrillin-1 and SIRT1, which are downregulated in skin dermal fibroblasts during aging and correlate with cellular stiffness and aging. The success of the present composition can also be measured using non-invasive imaging techniques, including (i) reflectance confocal microscopy (RCM), which allows visualization of structural changes related to aging, such as collagen degradation and dermal-epidermal junction changes in vivo; or (ii) optical coherence tomography (OCT), a high-resolution "virtual biopsy" method that quantifies structural skin changes such as fibrosis and dermal-epidermal junction abnormalities. Further, the success of the present composition can be determined by (i) fluorescence imaging (Fluorocoxib A), which targets cyclooxygenase-2 (COX-2), a marker expressed in aging or damaged tissues, allowing real-time imaging of early skin aging changes (e.g., a decrease of at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%); or (ii) ultrasonic imaging, which provides in vivo cross-sectional images of the skin and allows for the assessment of skin thickness and density, reflecting changes in collagen degradation and structural changes associated with aging (e.g., an increase of skin thickness or density by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%). Example 19 – Measuring Loss of Proteostasis The success of the present composition in ameliorating the loss of proteostasis in a subject (e.g., a human subject) can be measured, for example, by making any of the following determinations: (i) an increase (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the expression of heat shock proteins (HSPs), such as HSP70, which are linked to proteostasis mechanisms in skin aging; (ii) improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the levels of extracellular matrix biomarkers such as Collagen V and Versican, which are associated with ECM degradation and protein aggregation in aged skin; or (iii) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in oxidation-related proteins such as Peroxiredoxins and SERPINs, which are altered in photoaged skin. The success of the present composition can also be measured by (i) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in Lamin B1 levels, a marker of cellular senescence and proteostasis loss in photoaged skin; (ii) changes (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in cytoskeletal proteins such as Keratins, which are linked to structural changes in aged skin; or (iii) changes (e.g., a decrease of at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in Tubulin Beta-3 Chain expression, which is altered in aged skin and serves as a biomarker for proteostasis loss. Further success of the present composition can be measured by determining (i) a reduction (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in the overexpression of Matrix Metalloproteinase-1 (MMP-1), which degrades collagen and is a hallmark of aging skin, along with reduced levels of tissue inhibitors of metalloproteinases (TIMP-1); (ii) improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in collagen structure, as detected by automated histological analysis, revealing collagen thinning and loss with aging; or (iii) improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in collagen and elastin fibers visualized by multiphoton imaging of dermal collagen and elastin. The success of the present composition can also be determined by improvements in nerve fiber biomarkers, such as intraepidermal and subepidermal nerve fibers (IENF, SENF), which are marked by reductions (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in PGP9.5 and TRPV1 in skin biopsies, tracking proteostasis loss in aging. The success of the present composition can also be measured by improvements (e.g., by at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) in ribosomal proteins and TRiC complex subunits, which are involved in protein synthesis and folding, with dysregulation leading to proteostasis issues in aging skin. Additionally, the success of the present composition can be evaluated using non- invasive imaging techniques, including optical coherence tomography (OCT), which provides "virtual biopsies" and quantifies skin fibrosis and proteostasis-related changes in aging skin. Finally, the success of the present composition can be measured by assessing the levels of senescence-related molecules (SRMs) such as ETF1, PLBD2, ASAH1, and MOXD1, which are linked to aging-related pathways and can be used to measure proteostasis loss (e.g., an increase of at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%) via transcriptomic and proteomic analysis.

[0002] References 1. The Aging Process, Denham Harman. Proceedings of the National Academy of Sciences of the United States of America, 1981. 2. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA, 2007. 3. Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials. Am. J. Clin. Nutr., 2013. 4. Multivitamins in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. JAMA, 2012. 5. A Mitochondrial Superoxide Signal Triggers Increased Longevity in Caenorhabditis elegans. PLOS Biology, 2017. 6. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc. Natl. Acad. Sci. USA 2009, 106, 8665–8670. 7. The Hallmarks of Aging, Cell, Vol.153, Issue 6, pp.1194-1217 (2013). 8. Senolytic drugs: from discovery to translation, J. Internal Medicine 2020 Nov. 288(5), 518-536.

Claims

What is claimed is:

1. A composition comprising (i) a first agent selected from the group consisting of a BH3 mimetic, an HDAC6 inhibitor, and a TLR-1, -2, and / or -4 inhibitor, and (ii) a second agent selected from the group consisting of a mitochondrial uncoupler, a Bcl-2 inhibitor, a p53 / MDM2 inhibitor, a HSP-90 inhibitor, a PI3K / AKT inhibitor, a BET inhibitor, and a general senolytic.

2. The composition of claim 1, further comprising at least one additional agent selected from the group consisting of a BH3 mimetic, an Mcl-1 inhibitor, a TLR-1, -2, and / or -4 inhibitor, a p53 / MDM2 inhibitor, a PI3K / AKT inhibitor, an HSP-90 inhibitor, a BET inhibitor, and a Bcl-2 inhibitor.

3. The composition of claim 1 or 2, further comprising at least one additional agent selected from the group consisting of a mitochondrial uncoupler, a BH3 mimetic, an Mcl-1 inhibitor, an HSP-90 inhibitor, a PI3K / AKT inhibitor, a BET inhibitor, and a Bcl-2 inhibitor.

4. The composition of any of claims 1-3, further comprising at least one additional agent selected from the group consisting of a mitochondrial uncoupler and a BH3 mimetic.

5. The composition of any of claims 1-4, further comprising an additional agent which is a mitochondrial uncoupler.

6. The composition of any of claims 1-5, further comprising (i) at least one additional agent selected from the group consisting of a BH3 mimetic, an Mcl-1 inhibitor, a TLR-1, -2, and / or -4 inhibitor, a p53 / MDM2 inhibitor, a PI3K / AKT inhibitor, an HSP-90 inhibitor, a BET inhibitor, a general senolytic, and a Bcl-2 inhibitor; (ii) at least one additional agent selected from the group consisting of a mitochondrial uncoupler, a BH3 mimetic, an Mcl-1 inhibitor, an HSP-90 inhibitor, a PI3K / AKT inhibitor, a BET inhibitor, and a Bcl-2 inhibitor; (iii) at least one additional agent selected from the group consisting of a mitochondrial uncoupler and a BH3 mimetic; and / or (iv) an additional agent which is a mitochondrial uncoupler.

7. The composition of any of claims 1-6, wherein one or more of the agents in the composition is formulated for delayed release and / or extended release.

8. A composition comprising (i) the composition of any of claims 1-7 and (ii) a pharmaceutically acceptable carrier.

9. The composition of claim 8, wherein the composition is suitable for dermal administration.

10. The composition of claim 8 or 9, wherein the composition comprises one or more bioavailability enhancers and / or one or more skin penetration enhancers.

11. The composition of any of claims 1-8, wherein the composition is in a form selected from the group consisting of a food, a nutritional supplement, a nutraceutical, an injectable, and a skincare product.

12. The composition of claim 11, wherein the skincare product is a skin cream, serum, or gel.

13. The composition of claim 12, wherein the skincare product is a facial skin cream, a facial serum, or a facial gel.

14. The composition of any of claims 11-13, wherein the skincare product is a face mask.

15. The composition of claim 11, wherein the nutritional supplement is an orally administered nutritional supplement.

16. A method for selectively reducing the number of senescent cells in a subject comprising administering to the subject the composition of any of claims 1-15.

17. The method of claim 16, wherein the senescent cells are selected from the group consisting of senescent liver-related cells, senescent adipose tissue-related cells, senescent vascular-related cells, senescent connective tissue-related cells, senescent nervous system-related cells, senescent immune-related cells, senescent progenitorcells, senescent blood-related cells, senescent skin-related cells, senescent epithelial cells, senescent gland-related cells, senescent retinal cells, senescent beta cells, senescent ovarian cells, senescent hematopoietic stem cells, and combinations thereof.

18. A method for selectively reducing the number of senescent cells in a subject’s skin comprising administering to the subject’s skin the composition of any of claims 1- 15.

19. The method of claim 18, wherein the method comprises topically administering the composition to the subject’s skin.

20. The method of claim 19, wherein the method comprises topically administering the composition to the subject’s face.

21. The method of claim 19, wherein the method comprises topically administering the composition to the subject’s hands, neck, scalp, and / or décolleté area.

22. The method of any of claims 16-21, wherein the subject is a human.

23. The method of any of claims 16-21, wherein the subject is a rodent, a rabbit, a cat, a dog, or a horse.

24. An article of manufacture comprising a face mask having releasably affixed thereto the composition of any of claims 1-10, 12, and 13, wherein, when the subject wears the face mask, the composition is administered to the subject’s face.