Chondroitin and collagen peptide-based method for slowing senescence and prolonging life

Abstract

The present invention provides a composition comprising (i) chondroitin and / or collagen peptide and (ii) at least one substance selected from the group consisting of butyric acid, butyric acid equivalents, trehalose, trehalose equivalents, spermidine and spermidine equivalents. The invention also provides related pharmaceutical compositions, methods for improving senescence profile in a subject, and articles of manufacture.

Description

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 339,094, filed on May 6, 2022, the contents of which are incorporated herein by reference.

[0002] Various publications are cited throughout this application. The disclosures of these publications are incorporated herein by reference in order to more fully describe the prior art to which this invention pertains. Technical Field

[0003] The present invention relates to compositions and methods for improving one or more hallmarks of aging in a subject. Background Art

[0004] Physically, aging is characterized by the accumulation of molecular and cellular damage that leads to a deterioration in physiological function and normal homeostasis and increases the risk of frailty, weakness, disability, age-related diseases, and ultimately death.

[0005] For a long time, one of the main causes of aging is considered to be oxidative damage, as promoted and announced by Denham Harman's free radical theory of aging (1). According to this outdated theory, antioxidants have the ability to neutralize free radicals, thereby slowing down the aging process. However, studies have shown that most antioxidants do not slow down aging, and may even shorten lifespan or offset the beneficial effects of exercise (2-6). However, in the past 15 years, a better understanding of the aging process has emerged, resulting in an understanding of the various mechanisms and causes of aging. These include, for example, epigenetic disorders, epitranscriptome disorders, protease reduction (protein toxicity), mitochondrial dysfunction, genome damage, telomere shortening and depletion, transcriptome disorders, lysosomal dysfunction and cross-linking leading to the formation of senescent cells, decreased stem cell function and number, changes in the extracellular environment (e.g., changes to a proinflammatory environment), and changes in intercellular communication. These changes lead to an increased risk and occurrence of aging phenotypes and aging-related diseases such as heart disease, neurodegenerative diseases (eg, Alzheimer's disease or vascular dementia), osteoporosis, osteoarthritis, macular degeneration, renal dysfunction, etc.

[0006] There remains an unmet need for superior formulations that improve these hallmarks of aging. Summary of the invention

[0007] The present invention provides a composition comprising (i) chondroitin and / or collagen peptide and (ii) at least one substance selected from butyric acid, butyric acid equivalents, trehalose, trehalose equivalents, spermidine and spermidine equivalents.

[0008] The present invention also provides a pharmaceutical composition comprising (i) the composition of the present invention and (ii) a pharmaceutically acceptable carrier.

[0009] The present invention also provides a method for improving at least one characteristic of aging in a subject, comprising administering to the subject a composition of the present invention, wherein the characteristic of aging is selected from genomic instability, telomere attrition, epigenetic changes, loss of protein homeostasis, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, transcriptome dysregulation, cross-linking, and altered intercellular communication.

[0010] Finally, the present invention provides an article comprising (i) a composition of the present invention, wherein the composition does not contain butyric acid or butyric acid equivalents, and (ii) butyric acid and / or butyric acid equivalents in separate compartments. The present invention also provides an article comprising a composition containing butyric acid or butyric acid equivalents of the present invention, wherein (i) butyric acid and / or butyric acid equivalents and (ii) other components of the composition are located in separate compartments. DETAILED DESCRIPTION

[0011] The present invention provides compositions and methods for ameliorating a range of characteristics of aging in a subject.

[0012] definition

[0013] In this application, certain terms used shall have the meanings described below.

[0014] As used herein, "administering" means delivering a substance to a subject's body by any known method, with respect to a substance. Specific modes of administration include, but are not limited to, oral, sublingual, parenteral, intraperitoneal, intravenous, intraarterial, transdermal, intramuscular, rectal, transbuccal, intranasal, liposome, by inhalation, vaginally, intraocularly, topically (e.g., by catheter or stent), subcutaneously, intrathecally, or intrafatally. Preferably, the composition of the present invention is administered orally.

[0015] In addition, in the present invention, one or more conventionally used pharmaceutically acceptable carriers can be used to prepare various compositions. Such carriers are well known to those skilled in the art. For example, oral delivery systems include, for example, tablets, capsules, and powders (e.g., powders that can be added to water to form drinkable preparations). These can include excipients, such as binders (e.g., hydroxypropyl methylcellulose, polyvinyl pyrrolidone, other cellulose materials, and starch), diluents (e.g., lactose and other sugars, starch, dicalcium phosphate, and cellulose materials), disintegrants (e.g., starch polymers and cellulose materials), and lubricants (e.g., stearates and talc). In one embodiment, the oral delivery system is a powder and includes one or more of xylitol, erythritol, malic acid, flavoring agents, silicon dioxide, calcium silicate, and rebaudioside A.

[0016] As used herein, the term "signatures of aging" (used synonymously with "age-related signatures" and "signatures associated with aging") includes, but is not limited to, any of the following: genomic instability, telomere attrition, epigenetic alterations, loss of protein homeostasis, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, transcriptome dysregulation, cross-linking, and altered intercellular communication. These signatures are known and have been extensively studied by C. López Otín, et al. (7).

[0017] As used herein, the term "ameliorating" when used in reference to a characteristic of aging includes, but is not limited to (i) slowing, halting, reversing, or preventing the progression of the characteristic, (ii) slowing, halting, reversing, or preventing the progression of a symptom of the characteristic, (iii) preventing or reducing the likelihood of recurrence of the characteristic, and / or (iv) preventing or reducing the likelihood of recurrence of a symptom of the characteristic. In one embodiment, treating a subject having a characteristic of aging means (i) reversing the progression of the characteristic, ideally to the point of eliminating the characteristic, and / or (ii) reversing the progression of a symptom of the characteristic, ideally to the point of eliminating the symptom.

[0018] As used herein, "butyrate equivalents" include, but are not limited to, histone deacetylase (HDAC) inhibitors other than butyrate. These include, for example, butyric acid, butyrates (e.g., calcium butyrate, sodium butyrate, potassium butyrate, ammonium butyrate, and lithium butyrate), tributyrates, tributyrin, butyric glycerides, glyceryl tributyrate, phenyl butyrate, methyl butyrate, sodium phenylbutyrate, glycerides of butyric acid, amide derivatives of butyric acid, β-hydroxybutyric acid (BHB), β-hydroxybutyric acid, β-hydroxybutyric acid (BHB) derivatives, β-hydroxybutyrates (e.g., potassium β-hydroxybutyrate, sodium β-hydroxybutyrate, calcium β-hydroxybutyrate, and magnesium β-hydroxybutyrate), ketones based on β-hydroxybutyric acid, ketoesters based on β-hydroxybutyric acid, esters based on β-hydroxybutyric acid, β-hydroxybutyric acid esters, β-hydroxybutyric acid Butanediol, β-hydroxybutyric acid glycerol, R-1,3-butanediol-R-3-hydroxybutyric acid, butanediol, R-1,3-butanediol, R-3-hydroxybutyric acid, dihexanoyl-1,3-butanediol, β-ketovaleric acid, β-hydroxyvaleric acid, valeric acid, valerian extract containing valerian acid, valerian root, valproate / ester, valeric acid, alkyl carboxylic acid, alkyl carboxylic acid derivatives, butyric acid and butyric acid precursors (e.g., fibers such as inulin, fructo-oligosaccharide (FOS), resistant starch, Hi-maize, potato starch, arabinoxylan and β-glucan), and combinations thereof. Butyric acid equivalents also include, but are not limited to, another alkane carboxylic acid or alkane carboxylic acid derivative (e.g., propionic acid or other short-chain fatty acids, such as formic acid, acetic acid, isovaleric acid, valeric acid, isocaproic acid, caproic acid, caprylic acid, lactic acid, succinic acid, pyruvic acid, and combinations thereof).

[0019] "Collagen peptides" as used herein include, but are not limited to, collagen, collagen hydrolysate, collagen tripeptide, collagen dipeptide, collagen monopeptide, derivatives thereof, and combinations thereof. The term "collagen peptides" as used herein may mean, for example, a single peptide or a single type of peptide, as well as a mixture of two or more types of such peptides.

[0020] As used herein, "phospholipids" include, but are not limited to, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, phosphatidic acid, phosphoinositides, phosphatidylinositol, phosphatidylinositol phosphate (PIP), phosphatidylinositol bisphosphate (PIP2), phosphatidylinositol triphosphate (PIP3), phosphatidyl esters, glycerophospholipids, acetal phospholipids, ether lipids, sphingomyelin, and derivatives and combinations thereof.

[0021] "Polyamine" used herein includes but is not limited to spermidine, putrescine, spermine, norspermidine, acetyl spermidine, diacetyl spermidine, methylated spermidine, spermidine salts, and derivatives and combinations thereof. The source of polyamines includes but is not limited to wheat germ, wheat germ extract, soybean, soybean extract, spermidine or other extracts with high polyamine content, and foods rich in spermidine.

[0022] As used herein, "sugars that support protein homeostasis" include, but are not limited to, trehalose, trehalose polysaccharides, mannitol, glucosamine, acetylglucosamine, galactosamine, mannosamine, and derivatives and combinations thereof.

[0023] "Spermidine equivalents" used herein include, but are not limited to, putrescine, spermine, norspermidine, acetyl spermidine, diacetyl spermidine, methylated spermidine, methylated polyamines, spermidine salts, and other polyamines that help protect cells from oxidative damage. Spermine and its equivalents are present in, for example, wheat germ, wheat germ extract, soybean, and soybean extract.

[0024] The term "subject" as used herein includes, but is not limited to, mammals, such as humans, non-human primates, dogs, cats, horses, sheep, goats, cattle, rabbits, pigs, rats, and rodents (e.g., mice). In the case where the subject is a human, the subject can be of any age. For example, the subject can be 60 years old or older, 65 years old or older, 70 years old or older, 75 years old or older, 80 years old or older, 85 years old or older, or 90 years old or older. Alternatively, the subject can be 50 years old or younger, 45 years old or younger, 40 years old or younger, 35 years old or younger, 30 years old or younger, 25 years old or younger, or 20 years old or younger.

[0025] As used herein, "trehalose equivalents" include, but are not limited to, mannitol, glucosamine, acetylglucosamine, galactosamine, mannosamine, glycerol, erythritol, xylitol, and other sugar-based molecules that help protect cells from stress and / or ameliorate protein toxicity.

[0026] Some embodiments of the present invention

[0027] The present invention provides compositions and methods for improving the characteristics of aging. These compositions contain certain combinations of substances that act synergistically to address the characteristics of aging, such as genomic instability, telomere attrition, epigenetic changes, loss of protein homeostasis, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. The present invention also provides related products.

[0028] Specifically, the present invention provides a composition comprising (i) chondroitin and / or collagen peptides and (ii) at least one substance selected from butyric acid, butyric acid equivalents, trehalose, trehalose equivalents, spermidine and spermidine equivalents.

[0029] In one embodiment of the composition of the present invention, the composition comprises (i) chondroitin and (ii) at least one substance selected from butyric acid, butyric acid equivalents, trehalose, trehalose equivalents, spermidine and spermidine equivalents. Preferably, the composition comprises chondroitin, butyric acid, trehalose and spermidine.

[0030] In another embodiment of the composition of the present invention, the composition comprises (i) collagen peptides and (ii) at least one substance selected from butyric acid, butyric acid equivalents, trehalose, trehalose equivalents, spermidine and spermidine equivalents. Preferably, the composition comprises collagen peptides, butyric acid, trehalose and spermidine.

[0031] In another embodiment, the composition comprises (i) chondroitin, (ii) collagen peptides and (iii) at least one substance selected from butyric acid, butyric acid equivalents, trehalose, trehalose equivalents, spermidine and spermidine equivalents. In a preferred embodiment, the composition comprises chondroitin, collagen peptides, butyric acid, trehalose and spermidine.

[0032] In one embodiment of the composition of the present invention, the trehalose equivalent is mannitol, glucosamine, acetylglucosamine, galactosamine, mannosamine, glycerol, erythritol or xylitol. In another embodiment, the spermidine equivalent is putrescine, spermine, norspermidine, acetyl spermidine, diacetyl spermine, methylated spermidine, methylated polyamines or spermidine salts. In another embodiment, the butyric acid equivalent is acetic acid.

[0033] In one example, the composition comprises 50mg to 6,000mg chondroitin, 50mg to 20,000mg collagen peptides, 50mg to 12,000mg butyric acid, 0.1g to 50g trehalose and 0.1mg to 30mg spermidine. In another example, the composition comprises 400mg to 1,200mg chondroitin, 1,000mg to 5,000mg collagen peptides, 400mg to 1,200mg butyric acid, 1g to 20g trehalose and 0.2mg to 20mg spermidine. In a preferred embodiment, the composition comprises 800mg chondroitin, 3,000mg collagen peptides, 800mg butyric acid, 5g trehalose and 2mg spermidine. In another preferred embodiment, the composition comprises 1,200mg chondroitin, 5,000mg collagen peptides, 1,100mg butyric acid, 10g trehalose and 2mg spermidine. Optionally, the composition of the present invention comprises one or more sweeteners, such as but not limited to erythritol, maltitol, mannitol, sorbitol, xylitol, isomalt, lactitol, tagatose, monk fruit, inuline and stevia-derived substances.

[0034] In another embodiment, the composition comprises (i) chondroitin, collagen peptides, butyric acid, trehalose and spermidine, and (ii) one or more substances selected from the following: ascorbic acid or ascorbic acid equivalents, α-ketoglutaric acid or α-ketoglutaric acid equivalents, pomegranate or pomegranate equivalents, phospholipids, B vitamins, and apigenin or apigenin equivalents. In one embodiment of the composition of the present invention, the composition comprises chondroitin, collagen peptides, butyric acid, trehalose, spermidine, ascorbic acid and α-ketoglutaric acid. In another embodiment, the composition comprises chondroitin, collagen peptides, butyric acid, trehalose, spermidine, ascorbic acid, α-ketoglutaric acid and phosphatidylcholine. In another embodiment, the composition comprises chondroitin, collagen peptides, butyric acid, trehalose, spermidine, ascorbic acid, α-ketoglutaric acid, phosphatidylcholine and B vitamins. In another embodiment, the composition comprises chondroitin, collagen peptides, butyric acid, trehalose, spermidine, ascorbic acid, alpha-ketoglutaric acid, phosphatidylcholine, B vitamins, and apigenin or apigenin equivalents. In one example, the composition comprises one or more substances selected from the following: 50 mg to 2,000 mg chondroitin, 200 mg to 10,000 mg collagen peptides, 100 mg to 7,000 mg butyric acid, 0.2 g to 20 g trehalose, 0.1 mg to 30 mg spermidine, 10 to 2,000 mg ascorbic acid, 100 mg to 10,000 mg alpha-ketoglutaric acid, 20 mg to 7,000 mg pomegranate or pomegranate equivalents, 40 mg to 5,000 mg phosphatidylcholine, 5% to 5,000% of the U.S. recommended daily allowance of B vitamins, and 50 mg apigenin. In another example, a composition comprises 400 mg to 1,200 mg chondroitin, 1,000 mg to 5,000 mg collagen peptides, 400 mg to 1,200 mg butyric acid, 1 g to 20 g trehalose, 0.2 mg to 20 mg spermidine, 500 mg ascorbic acid, 500 mg to 4,000 mg alpha-ketoglutaric acid, 100 mg to 3,000 mg pomegranate or pomegranate equivalent, 250 mg to 2,400 mg phosphatidylcholine, 100% to 300% of the U.S. Recommended Daily Allowance of B vitamins, and 50 mg apigenin. Preferably, in this example, the composition comprises the following daily doses: 1,200 mg chondroitin, 5,000 mg collagen peptides, 1,200 mg butyric acid, 10 g trehalose, 2 mg spermidine, 500 mg ascorbic acid, 1,100 mg α-ketoglutaric acid, 1,500 mg pomegranate or pomegranate equivalent, 1,200 mg phosphatidylcholine, 200% of the U.S. recommended daily allowance of B vitamins, and 50 mg apigenin. Optionally, the composition of the present invention comprises one or more sweeteners, such as, but not limited to, erythritol, maltitol, mannitol, sorbitol, xylitol, isomalt, lactitol, tagatose, monk fruit, inulin, and stevia-derived substances.

[0035] Preferably, one or more substances in the present composition are formulated for delayed release and / or extended release. In one embodiment of the present composition, chondroitin, collagen peptide, butyric acid, trehalose and spermidine are formulated for delayed release and / or extended release. In another embodiment of the present composition, butyric acid and spermidine and optional trehalose, alpha-ketoglutaric acid and ascorbic acid are formulated for delayed release and / or extended release. In another embodiment of the present composition, every kind of substance is formulated for delayed release and / or extended release. In another embodiment, the composition of the present invention comprises 1,200 mg delayed and / or extended release chondroitin, 5,000 mg delayed and / or extended release collagen peptides, 1,200 mg delayed and / or extended release butyric acid, 10 g delayed and / or extended release trehalose, 2 mg delayed and / or extended release spermidine, 500 mg delayed and / or extended release ascorbic acid, 1,100 mg delayed and / or extended release alpha-ketoglutaric acid, 1,500 mg delayed and / or extended release pomegranate or pomegranate equivalent, 1,200 mg delayed and / or extended release phosphatidylcholine, 200% of the U.S. Recommended Daily Allowance of B vitamins (in delayed and / or extended release form), and 50 mg delayed and / or extended release apigenin. Optionally, the composition of the present invention comprises one or more sweeteners, such as, but not limited to, erythritol, maltitol, mannitol, sorbitol, xylitol, isomalt, lactitol, tagatose, monk fruit, inulin and stevia-derived substances.

[0036] Each of the materials in the composition of the present invention is commercially available, for example in oral dosage form. The following are some non-limiting examples.

[0037] Chondroitin is commercially available, for example, in 600 mg capsules. Chondroitin is available as a sulfate salt, but all other forms are contemplated in the present invention. These include chains of acetylgalactosamine and glucuronic acid, mixtures of acetylgalactosamine and glucuronic acid, derivatives thereof, and combinations thereof. Collagen peptides are commercially available, for example, in a powder form of 5 g servings. Butyric acid is commercially available, for example, in capsule form. Butyric acid is available as a sodium salt, but all other salts of butyric acid are contemplated in the present invention. It is also contemplated that other histone deacetylase inhibitors are used in place of butyric acid for the present invention. Phosphatidylcholine (also referred to as phosphatidylcholine) is commercially available, for example, as a soft gel capsule. It is also contemplated that phosphatidylserine is used in place of phosphatidylcholine for the present invention.

[0038] B vitamins include thiamine (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), pantothenic acid, pyridoxine (vitamin B6), biotin (vitamin B7), folate and folic acid, and methylcobalamin (vitamin B12). They are commercially available, for example, individually or in combined "super B" forms (e.g., soft gelatin capsules and tablets). Additional B vitamins and their derivatives include, but are not limited to, nicotinamide, nicotinamide riboside, nicotinamide riboside (NR), nicotinamide, nicotinic acid, nicotinamide mononucleotide (NMN), nicotinic acid mononucleotide (NaMN), nicotinic acid riboside (NaR), nicotinamide adenine dinucleotide (NAD), NADH, nicotinamide riboside derivatives (or salts or prodrugs thereof or any molecule that can increase NAD+ levels in cells and organisms), choline, carnitine, adenine (vitamin B4), pyridoxal, pyridoxamine (vitamin B6), inositol (vitamin B8), myo-inositol, adenosine monophosphate (adenosine monophosphate), nicotinamide mono ... monophosphate (AMP), methylfolate (vitamin B9), cobalamin, cyanocobalamin, choline, dimethylglycine (DMG) (vitamin B16), trimethylglycine or betaine (TMG), benfotiamine, phosphatidylcholine, and derivatives and combinations thereof.

[0039] Apigenin is commercially available, for example, in capsules of 35 mg liposomal apigenin. Alpha-ketoglutarate (also known as alpha-ketoglutaric acid) is commercially available, for example, in 1,000 mg capsules. Alpha-ketoglutarate is available as a calcium salt, but all other forms of alpha-ketoglutarate are contemplated in the present invention. They include, for example, potassium alpha-ketoglutarate, sodium alpha-ketoglutarate, other salts of alpha-ketoglutarate, amino acid forms of alpha-ketoglutarate (e.g., arginine-alpha-ketoglutarate, alpha-ketoglutarate, and derivatives and combinations thereof).

[0040] Ascorbic acid (also known as vitamin C and ascorbate) is commercially available, for example, in 1,000 mg tablets. Also contemplated for use in the present invention in place of ascorbic acid are ascorbic acid derivatives. These derivatives include, but are not limited to, ascorbyl palmitate, tetrahexyldecyl ascorbic acid, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, sodium ascorbate, calcium ascorbate, ascorbic acid polypeptides, ascorbic acid peptides, ascorbyl glucosamine, ascorbyl glucoside, tetrahexyldecyl ascorbic acid, and combinations thereof.

[0041] Spermidine is commercially available, for example, in capsules of 400 mg of wheat germ extract containing 0.5 mg of spermidine. Trehalose is commercially available in powder form.

[0042] Pomegranate is, of course, widely available, as are its component active ingredients (i.e., "pomegranate equivalents"). Pomegranate equivalents include, but are not limited to, pomegranate extract, ellagic acid, urolithins, urolithins, urolithin A, urolithin B, urolithin C, urolithin D, ellagic acid metabolites, ellagitannins, urolithin glucuronides, ursolic acid, maresin, and foods high in ellagic acid (e.g., berries, black raspberries, blackberries, cloudberries, strawberries, red raspberries, cranberries, acai berries, apples, grapes, walnuts, chestnuts, pecans, and arctic blackberries).

[0043] Additional embodiments of the compositions of the present invention are described in the Examples section below.

[0044] The present invention also provides a pharmaceutical composition comprising (i) the composition of the present invention and (ii) a pharmaceutically acceptable carrier.

[0045] In a preferred embodiment, the composition of the present invention is in a form selected from food, powdered drink mix (mixed with water and taken orally), nutritional supplement, nutraceutical and skin care product. Preferably, each of these forms is self-administered daily.

[0046] The present invention also provides a method for improving at least one characteristic of aging in a subject, comprising administering a composition of the present invention to the subject (preferably once a day), wherein the characteristic of aging is selected from genomic instability, telomere attrition, epigenetic changes, loss of protein homeostasis, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, transcriptome dysregulation, cross-linking and altered intercellular communication.

[0047] In a preferred embodiment, the methods of the invention ameliorate genomic instability, telomere attrition, one or more epigenetic alterations, loss of proteostasis, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, transcriptome dysregulation, cross-linking, and altered intercellular communication.

[0048] In one embodiment, the methods of the present invention improve genomic instability. In another embodiment, the methods of the present invention improve telomere attrition. In another embodiment, the methods of the present invention improve one or more epigenetic changes. In another embodiment, the methods of the present invention improve loss of protein homeostasis. In another embodiment, the methods of the present invention improve nutrient sensing disorders. In another embodiment, the methods of the present invention improve mitochondrial dysfunction. In another embodiment, the methods of the present invention improve cellular aging. In another embodiment, the methods of the present invention improve stem cell exhaustion. In another embodiment, the methods of the present invention improve transcriptome disorders. In another embodiment, the methods of the present invention improve crosslinking. In another embodiment, the methods of the present invention improve changes in intercellular communication.

[0049] In another embodiment of the methods of the present invention, the methods improve at least two characteristics of aging in a subject. In another embodiment, the methods of the present invention improve at least three characteristics of aging in a subject. In another embodiment, the methods of the present invention improve at least four characteristics of aging in a subject. In another embodiment, the methods of the present invention improve at least five characteristics of aging in a subject. In another embodiment, the methods of the present invention improve at least six characteristics of aging in a subject. In another embodiment, the methods of the present invention improve at least seven characteristics of aging in a subject. In another embodiment, the methods of the present invention improve at least eight characteristics of aging in a subject. In another embodiment, the methods of the present invention improve at least nine characteristics of aging in a subject. In another embodiment, the methods of the present invention improve at least ten characteristics of aging in a subject. In another embodiment, the methods of the present invention improve at least eleven characteristics of aging in a subject.

[0050] For example, in one embodiment, the method of the present invention improves at least the following aging characteristics in a subject: genomic instability, epigenetic changes, and loss of protein homeostasis. In another embodiment, the method of the present invention improves at least the following aging characteristics in a subject: epigenetic changes, loss of protein homeostasis, and mitochondrial dysfunction. In another embodiment, the method of the present invention improves at least the following aging characteristics in a subject: epigenetic changes, loss of protein homeostasis, and dysregulated nutrient sensing. In another embodiment, the method of the present invention improves cell senescence or reduces the amount of senescent cells. In another embodiment, the method of the present invention improves cell senescence and stem cell exhaustion. In another embodiment, the method of the present invention improves mitochondrial dysfunction and loss of protein homeostasis. In another embodiment, the method of the present invention improves epigenetic changes and loss of protein homeostasis. In another embodiment, the method of the present invention improves intercellular communication changes and dysregulated nutrient sensing. In another embodiment, the method of the present invention improves intercellular communication changes and stem cell exhaustion. In another embodiment, the method of the present invention improves stem cell exhaustion and epigenetic changes. In another embodiment, the method of the present invention improves epigenetic changes and mitochondrial dysfunction. In another embodiment, the method of the present invention improves epigenetic changes, loss of protein homeostasis, and mitochondrial dysfunction. In another embodiment, the methods of the present invention improve stem cell exhaustion, cell aging, and altered intercellular communication. In another embodiment, the methods of the present invention improve epigenetic changes, cell aging, and mitochondrial dysfunction. In another embodiment, the methods of the present invention improve nutrient sensing disorders, mitochondrial dysfunction, and loss of protein homeostasis. In another embodiment, the methods of the present invention improve epigenetic changes, loss of protein homeostasis, mitochondrial dysfunction, and cell aging.

[0051] The present invention also contemplates administering the compositions of the present invention to a subject to achieve one or more of the following goals: (i) increase lifespan, extend healthy lifespan, and / or increase stress resistance; (ii) slow aging; (iii) reduce, alleviate, and / or slow aging-related diseases, aging-related symptoms, and / or age-related damage; (iv) reduce the risk of, prevent, inhibit the onset of, or treat a disease, such as cardiovascular disease (e.g., atherosclerosis, hypertension, heart failure, cardiac hypertrophy, coronary syndrome, heart valve dysfunction, arterial and valve calcification, or stroke), metabolic disorders (e.g., metabolic syndrome, high blood cholesterol, high serum triglycerides, elevated serum HbA1c, insulin resistance, insulin resistance disorder, hyperglycemia, decreased insulin sensitivity, diabetes, obesity, thyroid disorder, metabolic syndrome, fatty liver, steatohepatitis, hepatic steatosis, or diabetic retinopathy), cancer, cachexia, frailty, sarcopenia, neurodegenerative diseases (e.g., Alzheimer's disease, vascular dementia, Lewy body disease, disease), frontotemporal dementia, Parkinson disease, mild cognitive impairment, amyotrophic lateral sclerosis, or Huntington's disease), neuropathy, eye disease (e.g., macular degeneration or cataracts), lethargy, musculoskeletal disease (e.g., rheumatoid arthritis, osteoarthritis, osteoporosis, or muscular dystrophy), lung disease (e.g., pulmonary fibrosis, chronic obstructive pulmonary disease, disease, COPD), emphysema, increased susceptibility to aging-related lung infections (including pneumonia), aging-related gastrointestinal diseases (e.g., constipation, decreased gastric and intestinal motility, gastroparesis, polyps, intestinal dysbiosis, colitis or inflammatory bowel disease), blood disorders (e.g., leukemia, lymphoma, anemia, platelet disorders, coagulopathy, multiple myeloma, myelodysplastic syndrome or myeloproliferative disorders), infertility, decreased fertility, increased risk of aging-related cancer or proliferative diseases, disorders caused or exacerbated by senescent cells, aging-related skin diseases, psoriasis, senescence Age-related kidney disease, sepsis or sleep disorders; (v) improve and / or reduce physiological stress and dysfunction of cells and organisms caused by surgery, exercise, combat or certain work environments; and (vi) inhibit the origin and progression of the following: weight gain, wrinkles, skin sagging, skin aging, endurance loss, vision loss, hearing loss, sarcopenia (i.e., loss of muscle mass), insulin resistance, fat deposition (e.g., abdominal fat deposition), hair graying, hair loss, baldness, loss of libido, erectile dysfunction, memory problems, cognitive decline, attention problems, memory problems, sleep disorders or emotional disorders.

[0052] In a preferred embodiment of the method of the present invention, the subject is a human. In another embodiment of the method of the present invention, the subject is a rodent, rabbit, cat, dog or horse.

[0053] Finally, the present invention provides an article comprising (i) a composition of the present invention, wherein the composition does not contain butyric acid or butyric acid equivalents, and (ii) butyric acid and / or butyric acid equivalents in separate compartments. The present invention also provides an article comprising a composition containing butyric acid or butyric acid equivalents of the present invention, wherein (i) butyric acid and / or butyric acid equivalents and (ii) other components of the composition are located in separate compartments.

[0054] In one embodiment of these products, butyric acid and / or butyric acid equivalents are the only substances that are encapsulated separately (i.e., separately) (e.g., in an extended release form, while the other substances are in a non-extended release form). In another embodiment, multiple substances are encapsulated separately (e.g., in an extended release form). For example, the following embodiments are contemplated: (i) each of chondroitin, collagen peptides, butyric acid, trehalose, and spermidine is encapsulated separately; (ii) each of chondroitin, collagen peptides, butyric acid, and spermidine is encapsulated separately; (iii) each of chondroitin, collagen peptides, butyric acid, and trehalose is encapsulated separately; (iv) each of chondroitin, collagen peptides, and butyric acid is encapsulated separately; (v) each of butyric acid, trehalose, and spermidine is encapsulated separately; (vi) each of butyric acid and spermidine is encapsulated separately; and (vii) each of butyric acid and trehalose is encapsulated separately.

[0055] An advantage of the product of the present invention is that the unpleasant-tasting butyric acid and / or its unpleasant-tasting equivalents are separated from the other components of the composition of the present invention, thereby facilitating the oral administration of the entire composition. In one example, the product of the present invention comprises (i) chondroitin, collagen peptides, trehalose and spermidine (and optionally other substances as described herein), which are blended into a nutritional bar for oral use, and (ii) microcapsules (or microspheres) of butyric acid and / or butyric acid equivalents, which are in the nutritional bar. In another example, the product of the present invention comprises (i) chondroitin, collagen peptides, trehalose and spermidine (and optionally other substances as described herein), which are formulated as a powdered beverage mix for oral use after combination with water, and (ii) one or more capsules of butyric acid and / or butyric acid equivalents, which are used for oral use in combination with a beverage. For example, in one embodiment, the article of manufacture of the invention comprises in separate compartments: (i) a composition (preferably in powder form) comprising 1,200 mg chondroitin, 5,000 mg collagen peptides, 10 g trehalose and 2 mg spermidine (and optionally 500 mg ascorbic acid, 1,200 mg α-ketoglutaric acid, 1,500 mg pomegranate or pomegranate equivalent, 1,200 mg phosphatidylcholine (or phosphatidylserine), 200% of the U.S. recommended daily allowance of B vitamins, and 50 mg apigenin), and (ii) 1,200 mg butyric acid or butyric acid equivalent (preferably in capsule form). In order to reduce the unpleasant smell and taste of butyric acid, a triacylglyceride or diacylglyceride form of butyric acid (e.g., tributyrin) can be used.

[0056] In the methods of the present invention, it is contemplated that the subject is orally administered a composition of the present invention daily. The following dosages are contemplated, but are not limited thereto: (i) 1,200 mg chondroitin (or optionally, 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 900 mg, 1,000 mg, 1,100 mg, 1,200 mg chondroitin) 0 mg, 1,300 mg, 1,400 mg, 1,500 mg, 1,600 mg, 2 g, 3 g, 4 g, 5 g, 10 g and 20 g); (ii) 5,000 mg collagen peptide (or optionally, 10 mg, 20 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 1,000 mg, 1,500 mg, 2,000 mg thereof); , 2,500 mg, 3,500 mg, 4,000 mg, 5,000 mg, 6,000 mg, 8,000 mg, 10 g, 20 g, 30 g, 40 g and 50 g); (iii) 1,100 mg butyric acid (or optionally, 80 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 900 mg, 1,00 0 mg, 1,100 mg, 1,200 mg, 1,300 mg, 1,400 mg, 1,500 mg and 1,600 mg); (iv) 10 g of trehalose (or optionally, any one of 0.5 g, 1 g, 2 g, 3 g, 4 g, 6 g, 7 g, 8 g, 9 g, 10 g, 15 g, 20 g, 25 g and 30 g thereof); (v) 2 mg of spermidine (or optionally, any one of 0.2 mg, 0.(vi) 500 mg of ascorbic acid (or optionally, 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 120 mg, 140 mg, 160 mg, 180 mg, 200 mg, 400 mg, 500 mg, 1,000 mg, 1,500 mg thereof); g, 2,000 mg, 3,000 mg, 4,000 mg and 5,000 mg thereof); (vii) 1,100 mg α-ketoglutaric acid (or optionally, 20 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1,200 mg, 1,400 mg, 1,600 mg, 1,800 mg, 2,000 mg, 3,000 mg, 4,000 mg, 5,000 mg thereof); 00mg, 6,000mg, 7,000mg, 8,000mg, 9,000mg and 10,000mg); (viii) 1,500mg pomegranate or pomegranate equivalent (or optionally, any one of 150mg, 300mg, 500mg, 1,000mg, 2,000mg, 3,000mg, 4,000mg and 5,000mg thereof); (ix) 1,200mg phosphatidylcholine (or optionally, any one of 100mg, 200mg, 300mg, 40 0 mg, 500 mg, 600 mg, 800 mg, 1,000 mg, 1,500 mg, 2,000 mg and 3,000 mg); (x) 200% of the U.S. recommended daily allowance of B vitamins; and (xi) 50 mg of apigenin (or optionally, any one of 5 mg, 10 mg, 20 mg, 30 mg, 40 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 200 mg, 500 mg, 1,000 mg and 2,000 mg thereof).

[0057] The following dosages are also contemplated for daily administration, but are not limited thereto: (i) 10 mg to 50 mg, 50 mg to 100 mg, 100 mg to 400 mg, 400 mg to 1,200 mg, 1,200 mg to 2 g, 2 g to 10 g, or 10 g to 20 g of chondroitin; (ii) 10 mg to 50 mg, 50 mg to 100 mg, 100 mg to 500 mg, 500 mg to 2,000 mg, 2,000 mg to 4, (iii) 80 mg to 200 mg, 200 mg to 400 mg, 400 mg to 1,200 mg, or 1,200 mg to 8,000 mg of butyric acid; (iv) 0.5 g to 1 g, 1 g to 3 g, 3 g to 10 g, or 10 g to 50 g of trehalose; (v) 0.2 mg to 0.5 mg, 0.5 mg to 1 mg, 1 mg to 5 mg , or 5 mg to 30 mg spermidine; (vi) 10 mg to 50 mg, 50 mg to 150 mg, or 150 mg to 5,000 mg ascorbic acid; (vii) 100 mg to 400 mg, 400 mg to 800 mg, 800 mg to 1,200 mg, or 1,200 mg to 8,000 mg alpha-ketoglutaric acid; (viii) 150 mg to 300 mg, 300 mg to 1,000 mg, or 1,000 mg mg to 10,000 mg pomegranate or pomegranate equivalents; (ix) 100 mg to 400 mg, 400 mg to 800 mg, 800 mg to 1,500 mg, or 1,500 mg to 6,000 phosphatidylcholine; (x) 50% to 300% of the U.S. Recommended Daily Allowance of B vitamins; and (xi) 5 mg to 10 mg, 10 mg to 30 mg, 30 mg to 70 mg, or 70 mg to 2,000 mg apigenin.

[0058] The following three dosage regimens (i) are also intended for daily oral administration (in delayed release and / or extended release form, as well as in non-delayed release, non-extended release form), and (ii) are intended for use in the compositions and preparations of the present invention. They include, but are not limited to, the following: (i) 300 mg chondroitin, 1,250 mg collagen peptides, 275 mg butyric acid, 2.5 g trehalose, 0.5 mg spermidine, 125 mg ascorbic acid, 275 mg α-ketoglutaric acid, 375 mg pomegranate or pomegranate equivalent, 300 mg phosphatidylcholine, 50% of the U.S. recommended daily allowance of B vitamins, and 12.5 mg apigenin; (ii) 600 mg chondroitin, 2,500 mg collagen peptides, 550 mg butyric acid, 5 g trehalose, 1 mg spermidine, 250 mg ascorbic acid, 550 mg mg alpha-ketoglutaric acid, 750 mg pomegranate or pomegranate equivalent, 600 mg phosphatidylcholine, 100% of the U.S. recommended daily value of B vitamins, and 25 mg apigenin; and (iii) 900 mg chondroitin, 3,750 mg collagen peptides, 825 mg butyric acid, 7.5 g trehalose, 1.5 mg spermidine, 375 mg ascorbic acid, 825 mg alpha-ketoglutaric acid, 1,125 mg pomegranate or pomegranate equivalent, 900 mg phosphatidylcholine, 150% of the U.S. recommended daily value of B vitamins, and 37.5 mg apigenin.

[0059] The present invention will be better understood by reference to the following examples, however, those skilled in the art will readily appreciate that the specific examples detailed are merely illustrative of the invention as more fully described in the claims which follow.

[0060] Example

[0061] Example 1 - Some other embodiments of the composition of the present invention

[0062] Combinations of the following additional substances are contemplated for the present compositions, but are not limited thereto.

[0063] One additional combination comprises (i) chondroitin and (ii) butyric acid or a butyric acid equivalent. Another additional combination comprises (i) chondroitin and (ii) trehalose or a trehalose equivalent. Another additional combination comprises (i) chondroitin and (ii) spermidine or a spermidine equivalent. Another additional combination comprises (i) chondroitin and (ii) butyric acid or a butyric acid equivalent and (iii) trehalose or a trehalose equivalent. Another additional combination comprises (i) chondroitin, (ii) butyric acid or a butyric acid equivalent and (iii) spermidine or a spermidine equivalent. Another additional combination comprises (i) chondroitin, (ii) trehalose or a trehalose equivalent and (iii) spermidine or a spermidine equivalent. Another additional combination comprises (i) chondroitin, (ii) trehalose or a trehalose equivalent and (iii) spermidine or a spermidine equivalent.

[0064] Another additional combination comprises (i) collagen peptides and (ii) butyric acid or a butyric acid equivalent. Another additional combination comprises (i) collagen peptides and (ii) trehalose or a trehalose equivalent. Another additional combination comprises (i) collagen peptides and (ii) spermidine or a spermidine equivalent. Another additional combination comprises (i) collagen peptides, (ii) butyric acid or a butyric acid equivalent and (iii) trehalose or a trehalose equivalent. Another additional combination comprises (i) collagen peptides, (ii) butyric acid or a butyric acid equivalent and (iii) spermidine or a spermidine equivalent. Another additional combination comprises (i) collagen peptides, (ii) trehalose or a trehalose equivalent and (iii) spermidine or a spermidine equivalent.

[0065] Another additional combination comprises (i) chondroitin, (ii) collagen peptides and (iii) butyric acid or butyric acid equivalents. Another additional combination comprises (i) chondroitin, (ii) collagen peptides and (iii) trehalose or trehalose equivalents. Another additional combination comprises (i) chondroitin, (ii) collagen peptides and (iii) spermidine or spermidine equivalents. Another additional combination comprises (i) chondroitin, (ii) collagen peptides and (iii) butyric acid or butyric acid equivalents and (iv) trehalose or trehalose equivalents. Another additional combination comprises (i) chondroitin, (ii) collagen peptides, (iii) butyric acid or butyric acid equivalents and (iv) spermidine or spermidine equivalents. Another additional combination comprises (i) chondroitin, (ii) collagen peptides, (iii) butyric acid or butyric acid equivalents and (iv) spermidine or spermidine equivalents. Another additional combination comprises (i) chondroitin, (ii) collagen peptides, (iii) trehalose or trehalose equivalents and (iv) spermidine or spermidine equivalents.

[0066] Another additional combination comprises chondroitin, collagen peptides, butyric acid, trehalose, spermidine and ascorbic acid. Another additional combination comprises chondroitin, collagen peptides, butyric acid, trehalose, spermidine and alpha-ketoglutaric acid. Another additional combination comprises chondroitin, collagen peptides, butyric acid, trehalose, spermidine and pomegranate or pomegranate equivalent. Another additional combination comprises chondroitin, collagen peptides, butyric acid, trehalose, spermidine and phosphatidylcholine. Another additional combination comprises chondroitin, collagen peptides, butyric acid, trehalose, spermidine and B vitamins. Another additional combination comprises chondroitin, collagen peptides, butyric acid, trehalose, spermidine and apigenin. Another additional combination comprises chondroitin, collagen peptides, butyric acid, trehalose, spermidine, and ascorbic acid, alpha-ketoglutaric acid, pomegranate or pomegranate equivalents, phosphatidylcholine, B vitamins and apigenin.

[0067] Another additional combination comprises a histone deacetylase inhibitor, a polyamine, a sugar to support protein homeostasis, a chondroitin-based substance, a collagen peptide, an ascorbic acid derivative, alpha-ketoglutaric acid, a pomegranate derivative, a phospholipid, B vitamins and apigenin.

[0068] Another additional combination comprises a histone deacetylase inhibitor, a polyamine, a sugar to support protein homeostasis, a chondroitin-based substance, a collagen peptide, an ascorbic acid derivative, alpha-ketoglutarate, a phospholipid, B vitamins and apigenin.

[0069] Another additional combination comprises a histone deacetylase inhibitor, a polyamine, a sugar to support protein homeostasis, a chondroitin-based substance, a collagen peptide, an ascorbic acid derivative, alpha-ketoglutarate, a phospholipid and B vitamins.

[0070] Another additional combination comprises a histone deacetylase inhibitor, a polyamine, a sugar to support protein homeostasis, a chondroitin-based substance, a collagen peptide, an ascorbic acid derivative and alpha-ketoglutarate.

[0071] Another additional combination contains a histone deacetylase inhibitor, a polyamine, a sugar to support protein homeostasis, a chondroitin-based substance, and a collagen peptide.

[0072] Another additional combination comprises a histone deacetylase inhibitor, a polyamine, a sugar supporting protein homeostasis, and a chondroitin-based substance.

[0073] Another additional combination comprises a histone deacetylase inhibitor, spermidine, trehalose, chondroitin, collagen peptides, ascorbic acid derivatives, alpha-ketoglutaric acid, ellagic acid, phospholipids, B vitamins and apigenin or an apigenin derivative.

[0074] Another additional combination comprises a histone deacetylase inhibitor, spermidine, trehalose, chondroitin, collagen peptides, ascorbic acid derivatives, phospholipids, B vitamins and apigenin.

[0075] Another additional combination comprises a histone deacetylase inhibitor, spermidine, chondroitin, collagen peptides, ascorbic acid derivatives, phospholipids and B vitamins.

[0076] Another additional combination comprises butyric acid, spermidine, chondroitin sulfate, collagen peptides, ascorbic acid derivatives, alpha-ketoglutaric acid, phosphatidylcholine and B vitamins.

[0077] Another additional combination includes butyric acid, spermidine, chondroitin sulfate, collagen peptides, ascorbic acid, alpha-ketoglutaric acid, phosphatidylcholine, and B vitamins.

[0078] Another additional combination comprises butyric acid, spermidine, trehalose, chondroitin sulfate, collagen peptides, ascorbic acid derivatives and phosphatidylcholine.

[0079] Another additional combination comprises trehalose, spermidine, chondroitin sulfate, collagen peptides, ascorbic acid derivatives, alpha-ketoglutaric acid, phosphatidylcholine and B vitamins.

[0080] Another additional combination comprises butyric acid, spermidine, chondroitin sulfate, collagen peptides, ascorbic acid derivatives, alpha-ketoglutaric acid, phosphatidylcholine and B vitamins.

[0081] Another additional combination comprises spermidine, chondroitin sulfate, collagen peptides, ascorbic acid derivatives, alpha-ketoglutaric acid, phosphatidylcholine and B vitamins.

[0082] Another additional combination comprises a supplement or nutraceutical containing a histone deacetylase inhibitor (such as but not limited to butyrate), spermidine, trehalose, chondroitin, collagen peptides, ascorbic acid derivatives, alpha-ketoglutaric acid, ellagic acid, phospholipids, B vitamins, and apigenin or an apigenin derivative.

[0083] Another additional combination comprises a food or treat containing a histone deacetylase inhibitor (eg, butyrate), spermidine, trehalose, chondroitin, collagen peptides, ascorbic acid derivatives, alpha-ketoglutaric acid, ellagic acid, phospholipids, B vitamins, and apigenin or an apigenin derivative.

[0084] Another additional combination comprises a food or treat containing a histone deacetylase inhibitor (e.g., butyrate), spermidine, trehalose, chondroitin, collagen peptides, ascorbic acid derivatives, alpha-ketoglutaric acid, ellagic acid, phospholipids, B vitamins, apigenin or apigenin derivatives, and all essential macronutrients (e.g., fat, carbohydrates, and protein) or a group of specific macronutrients (e.g., fat, carbohydrates, or protein).

[0085] Another additional combination comprises a food or treat containing spermidine, trehalose, chondroitin, collagen peptides, ascorbic acid derivatives, alpha ketoglutaric acid, pomegranate extract, phospholipids, B vitamins and apigenin.

[0086] Another additional combination includes a food or treat containing spermidine, trehalose, chondroitin, and collagen peptides.

[0087] Another additional combination comprises a skin cream, skin serum or skin care product containing: a histone deacetylase inhibitor (such as butyric acid), spermidine, trehalose, chondroitin, collagen peptides, ascorbic acid derivatives, alpha-ketoglutaric acid, ellagic acid, phospholipids, B vitamins and apigenin or an apigenin derivative.

[0088] In another further embodiment of the method of the invention, the daily dose administered comprises (i) 40 mg to 10,000 mg butyric acid (ideally 400 mg to 4,000 mg), (ii) 0.1 mg to 20 mg spermidine (average 1 mg to 6 mg spermidine), (iii) 0.2 g to 70 g trehalose, (iv) 20 mg to 4,000 mg chondroitin, (v) 20 mg to 15,000 mg collagen peptides, (vi) 10 to 5,000 mg ascorbic acid, (vii) 20 mg to 10,000 mg α-ketoglutaric acid (average =Approximately 1,100 mg), (viii) 10 mg to 10,000 mg pomegranate or pomegranate derivatives, or pomegranate extract containing 50 mg to 1,000 mg, or urolithin or pomegranate extract standardized to 30% punicalagin, or a pomegranate blend standardized to 20% punicic acid, or pomegranate extract standardized to contain 40% ellagic acid, (ix) 20 mg to 4,000 mg phosphatidylcholine (the average ideal dose is 1,200 mg), (x) 100% to 300% of the U.S. Recommended Daily Allowance of B vitamins, and (xi) 50 mg apigenin.

[0089] Example 2 - Measuring epigenetic dysregulation

[0090] The success of the compositions of the invention in improving 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, histone modification and / or chromatin pattern more closely resembles that of a younger person (e.g., 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 at least 100% similar); (ii) the epigenetic clock is increased in magnitude, or more closely resembles that of a younger person; (iii) an epigenetic DNA methylation clock (e.g., a Horvath clock or a Levine clock) that measures methylation of DNA in different regions of a subject's DNA that more closely resembles the DNA methylation pattern of a younger subject (e.g., 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 at least 100% similar); (iv) an epigenetic DNA methylation clock (e.g., a Horvath clock or a Levine clock) that shows that an adult subject has been rejuvenated for at least three months, one year, at least two years, or at least three years after administration of a composition of the invention (or wherein the epigenetic age or biological age has been reduced 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 at least 100% compared to the subject's chronological age); (e.g., 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 at least 100% similar); (v) the subject's transcriptome is more closely similar to the transcriptome of the younger subject (e.g., 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 at least 100% similar); (vi) the expression profile of ribosome-associated proteins and / or ribosome-associated RNA in the subject more closely resembles the expression profile of a younger organism (e.g., 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 at least 100% similar).or (vii) the subject's sirtuin levels have been increased (e.g., increased 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 at least 100%).

[0091] The success of the compositions of the invention in improving epigenetic disorder in a subject (e.g., a human subject) can also be measured, for example, by performing any of the following determinations: (i) an increase in the level of H3K9me3 in a subject (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 at least 100%); or (ii) an increase in the level of a heterochromatin protein (Hp1y) in a subject (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 at least 100%).

[0092] Example 3 - Measuring Cellular Senescence

[0093] The success of the compositions of the invention in improving cellular senescence in a subject (e.g., a human subject) can be measured, for example, by performing any of the following determinations: (i) a delay in the appearance of senescent cells or a delay in the transition of normal cells to senescent cells in vitro or in vivo (e.g., a delay of 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 at least 100%); and / or (ii) a reduction in the number of senescent cells in vitro or in vivo (e.g., a reduction 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 at least 100%). Senescence or a senescence-like state of a cell can be measured, for example, by one or more of the following: (i) an epigenetic profile, such as measuring epigenetic markers of senescence (e.g., changes in histone H3 lysine 9 and 27 trimethylation (altered levels of H3K9me3 and H3K27me3), altered levels of heterochromatin protein 1 (HP1) family proteins, increased levels of the histone variant macroH2A, and / or levels of the chromatin remodeling enzyme ATRX); (ii) changes in cell morphology that are similar to the morphology of senescent cells (e.g., increased size, flatter shape, accumulation of polyploid nuclei or DNA damage foci); (iii) changes in the levels of nuclear lamina propria-associated proteins (e.g., lamins) (e.g., decreased lamin B1); (iv) changes in heterochromatin that are more similar to the heterochromatin state of senescent cells (e.g., increased senescence-associated heterochromatic foci (SAHF)); (v) senescence-associated distention of satellites (e.g., increased ... (vi) changes in the secretory phenotype of senescent cells (e.g., the presence of a greater number of senescence-associated secretomes, which include, but are not limited to, cytokines, interleukins (e.g., IL-1, IL-2, IL-6, IL-8, and TNF-α), matrix metalloproteinases, pro-angiogenic factors, pro-inflammatory substances, and growth factors (e.g., vascular endothelial growth factor, insulin-like growth factor, and GM-CSF)).

[0094] The success of the compositions of the invention in improving cellular senescence in a subject (e.g., a human subject) can also be measured, for example, by performing any of the following determinations: (i) an increase in the level of H3K9me3 in a subject (e.g., an increase of 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 at least 100%); (ii) an increase in the level of H3K27me3 in a subject (e.g., an increase of 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 at least 100%); (e.g., a decrease of 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 at least 100%); (iii) a decrease in the level of P16INK4A in a subject (e.g., a decrease of 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 at least 100%); or (iv) a decrease in the level of one or more of p16, p53, p21, p14, p15, and β-galactosidase activity in a subject (e.g., a decrease of 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 at least 100%).

[0095] Example 4 - Measuring changes in intercellular communication

[0096] The success of the compositions of the invention in improving alterations in intercellular communication in a subject (e.g., a human subject) can be measured, for example, by determining a decrease in the level of one or more of IL-1, IL-2, IL-6, IL-8, IL-17a, and TNF-α signaling in the subject (e.g., a decrease of 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 at least 100%).

[0097] Example 5 - Measuring Autophagy

[0098] The success of the compositions of the invention in improving the reduction of 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., an increase of 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 at least 100%); (ii) an increase in any of phagophore formation, autophagosome formation, lysosome number, lysosomal activity, LC3 spots, lysosomal content (as determined, for example, using immunochemistry, electron microscopy, Western blotting, or flow cytometry) (e.g., an increase of 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 at least 100%). (iii) an increase in lysosomal acidity (e.g., an increase of 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 at least 100%); (iv) upregulation of the ubiquitin-proteasome system or (v) inhibition of mTOR or the mTOR pathway (e.g., inhibition of 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 at least 100%).

[0099] Example 6 - Measuring Cellular Oxidation

[0100] The success of the compositions of the invention in improving cellular oxidation in a subject (e.g., a human subject) can be measured, for example, by performing any of the following determinations: (i) a reduction in the level of 8-isoprostane in a subject (e.g., a reduction of 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 at least 100%); (ii) a reduction in the level of 8-hydroxydeoxyguanosine (8-OHdG) in a subject (e.g., a reduction of 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 at least 100%); or (iii) a reduction in the level of oxidized LDL, malondialdehyde (MDA), 4-HNA, lipid hydroperoxides, oxidized proteins, protein carbonylation and protein nitration (3-nitrotyrosine), advanced glycation end products (AGEs) in a subject.

[00136] In some embodiments, the present invention provides a reduction in the level of any of EGFR (EGFR) products, AGEs, and advanced oxidation protein products (e.g., a reduction of 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 at least 100%).

[0101] Example 7 - Measuring Telomere Fitness

[0102] The success of the compositions of the invention in improving telomere attrition in a subject (e.g., a human subject) can be measured, for example, by performing any of the following determinations: (i) an increase in telomere length in a subject (e.g., an increase of at least 0.01%, at least 0.1%, at least 0.5%, at least 1.0%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, or at least 50%); or (ii) an increase in mRNA expression of telomerase, TERT, TERC, or a telomerase-related gene (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 at least 100%).

[0103] Example 8 - Measuring stem cell fitness

[0104] The success of the compositions of the invention in improving 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., an increase of at least 1%, at least 2%, at least 5%). This increase can be measured in vitro or in vivo by, 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, β-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 receptor-9, GCNF / NR6A1, GFAP, Glut1, HOXB1, ID2, LRTM1, Meteorin, MSX1, Musashi-1, Musashi-2, Nestin, NeuroD1, Noggin, Notch-1, Notch-2, Nrf2, Nuclear stem cell factor (Nucleostemin), Numb, Otx2, Pax3, Pax6, PDGF Rα, PKCζ, Prominin 2, ROR2, RUNX1 / CBFA2, RXRα / NR2B1 (e.g., sFRP-2, SLAIN1, SOX1, SOX2, SOX9, SOX11, SOX21, SSEA-1, SSEA-4, TRAF-4, vimentin, and ZIC1); (iii) pluripotent stem cell markers (e.g., Oct4, NANOG, Sox2, and Myc); (iv) hematopoietic stem cell markers (e.g., CD34, CD59, and CD90 / Thy1); and (v) mesenchymal stem cell markers (e.g., CD105, CD90, CD73, CD44, CD45, CD29, CD166, Stro-1, CD106, and GSTT1).

[0105] Because measuring stem cells in vivo is difficult and expensive, the success of the compositions of the invention in ameliorating stem cell depletion can also be measured, for example, by performing the following preferred in vitro ("lab dish") assays (as well as in vivo assays): (i) an increase in stem cell number (e.g., an increase of 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 at least 100%); (ii) survival of the stem cells; (iii) an increase in the potency of the stem cells in vitro (and in vivo) (e.g., an increase of 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 at least 100%); (iv) an increase in the potency of the stem cells in vitro (and in vivo) (e.g., an increase of 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 at least 100%). (iv) an increase in stem cell quality as measured, for example, by an increase in stem cell growth, an increase in proliferation capacity, an increase in the ability to form colonies, or an increase in the ability to generate cells (e.g., an increase of 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 at least 100%); (v) an increase in stem cell lifespan as measured in hours (e.g., an increase of 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 at least 100%). or (vi) an increase (e.g., an increase of 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 at least 100%) in the resistance of stem cells to a cellular stressor (e.g., heat, cold, or a toxin).

[0106] The success of the compositions of the invention in ameliorating stem cell exhaustion in a subject (e.g., a human subject) can also be measured, for example, by performing any of the following determinations in vitro and in vivo: (i) improvement in stem cell function, such as, for example, by replicative capacity, potency, proliferation capacity, survival (such as measured, for example, over time (e.g., number of additional survival times) by exposing stem cells to physiological stressors and toxins), potency, and quality (e.g., stem cells have an increased number of replications or can give rise to a greater number of cells derived from stem cells or show increased markers of cell division (e.g., cell proliferation), or (ii) an improvement in the stem cell transcriptome (i.e., the transcriptome of the stem cells is more similar to the transcriptome of younger stem cells or more functional stem cells) (e.g., an improvement of 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 at least 100%). , at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 100%); (iii) an improvement in the stem cell proteome (i.e., the proteome of the stem cells is more similar to the proteome of younger stem cells or more functional stem cells) (e.g., an improvement of 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 at least 100%); or ( iv) an improvement in the stem cell epigenome (i.e., the epigenome of the stem cells is more similar to the epigenome of younger stem cells or more functional stem cells) (e.g., an improvement of 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 at least 100%), as assessed, for example, by measuring methylation or histone methylation patterns and comparing them to younger, more functional, or more potent stem cells.

[0107] Example 9 - Measurement of physiological biomarkers as indicators of stem cell fitness and senescent cell levels in an organism Markers

[0108] The success of the compositions of the invention in improving 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 reduction in the number and / or severity of skin wrinkles, as measured, for example, by wrinkle surface area (e.g., by 3D topography or profilometry); (ii) an increase in skin radiance, as measured, for example, by an identometer, a cutometer, a transepidermal water loss meter, a corneometer, or a skin transcriptome or proteome biomarker panel, which indicates improved skin function; (iii) an improvement in cognition, as measured, for example, by cognitive testing; (iv) an improvement in well-being, as measured, for example, by the Depressive Symptoms Scale; (v) a reduction in frailty, as measured, for example, by the International Frailty Scale or an activity scale (e.g., the Canadian Study on Health & Aging Clinical Frailty Scale). (e.g., improved endurance, improved balance, improved proprioception, improved mobility (as measured by the 6-minute walk test (6MWT), 4-meter gait speed test (4MGST), improved short physical performance battery (SPPB) score, or tests measuring balance, gait speed test, chair stand test, or other physical function markers), improved grip strength, improved power, increased activity level, improved 400-meter walk test, and improved arm curl test results); (viii) improved blood flow, as measured by 100% stamina, 100% stamina, and 100% stamina; (viii) improved blood flow, as measured by 200% stamina, 100% stamina, and 100% stamina; (viii) improved blood flow, as measured by 100% stamina, 100% stamina, and 100% stamina; (viii) improved blood flow, as measured by 200% stamina, 100% stamina, and 100% stamina. 3 The invention provides for the present invention to provide a method for improving the aging of the face by improving the blood flow to the tissue; (ix) reducing blood pressure; (x) improving vascular health, as measured, for example, by pulse wave velocity or flow-mediated vasodilation of the blood vessels; (xi) causing weight loss, waist circumference or BMI reduction, or abdominal fat volume reduction; (xii) improving heart rate variability (HRV); and (xiii) improving the AI-assessed facial aging curve (e.g., as measured by facial AI software that assesses wrinkle area, blood flow, or skin relaxation, for example).

[0109] Importantly, if stem cell health improves and cellular senescence decreases, many of the physiological biomarkers discussed in this example will also improve. This is particularly true for stem cells, as reducing senescence markers of stem cell decline (measurements of which are discussed above) improves physiological biomarkers.

[0110] Example 10 - Measuring genomic fitness

[0111] The success of the compositions of the invention in ameliorating genomic instability in a subject (e.g., a human subject) can be measured, for example, by determining a decrease (e.g., a decrease of 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 at least 100%) in the level of a biomarker of 8-hydroxydeoxyguanosine (8-OHdG), γ-H2AX, or DNA mutations (e.g., double strand breaks) in the subject.

[0112] Example 11 - Measuring Improvement of Nutritional Perception Disorders

[0113] The success of the compositions of the invention in improving dysregulated nutrient sensing in a subject (e.g., a human subject) can be measured, for example, by performing any of the following determinations: (i) an increase in the level of insulin sensitivity in a subject (e.g., an increase of 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 at least 100%); or (ii) a decrease in fasting glucose, fasting insulin, LDL, HbA1c, mTOR activity, or mitochondrial reactive oxygen species levels in a subject (e.g., a decrease of 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 at least 100%).

[0114] References

[0115] 1. D. Harman, The Aging Process. Proc. Nat'l. Acad. Sci. USA, 1981 Nov; 78 (11): 7124-8.

[0116] 2.G.Bjelakovic,etal.,Mortality in randomized trials of antioxidantsupplements for primary and secondary prevention:systematic review and meta-analysis.JAMA,2007,Feb 28;297(8):842-57.

[0117] 3.H.Macpherson,et al.,Multivitamin-multimineral supplementation andmortality:a meta-analysis of randomized controlled trials.Am.J.Cliin.Nutr.,2013,Feb;97(2):437-44.

[0118] 4.H.D.Sesso,et al.,Multivitamins in the prevention of cardiovasculardisease in men:the Physicians'Health Study II randomized controlledtrial.JAMA,2012,Nov 7;308(17):1751-60.

[0119] 5.W.Yang and S.Hekimi,A Mitochondrial Superoxide Signal TriggersIncreased Longevity in Caenorhabditis elegans.PLOS Biology,2010 Dec7;8(12):e1000556.

[0120] 6.M.Ristow,et al.,Antioxidants prevent health-promoting effects ofphysical exercise in humans.Proc.Nat’l.Acad.Sci.U.S.A.,2009,106,8665-8670.

[0121] 7.C.López-Otín,et al.,The Hallmarks of Aging,Cell,Vol.153,lssue 6,pp.1194-1217(2013).

[0122] 8.W.Zhang,et al.,The ageing epigenome and its rejuvenation.NatureReviews Mol.Cell Biol.,21,pages137-150(2020).

[0123] 9.P.Sen,et al.,Epigenetic Mechanisms of Longevity and Aging,Cell,2016,Aug11;166(4):822-839.

Claims

1. A composition comprising (i) chondroitin and / or collagen peptide and (ii) at least one substance selected from the group consisting of butyric acid, butyric acid equivalents, trehalose, trehalose equivalents, spermidine and spermidine equivalents.

2. The composition of claim 1, wherein the composition comprises (i) chondroitin and (ii) at least one substance selected from the group consisting of butyric acid, butyric acid equivalents, trehalose, trehalose equivalents, spermidine, and spermidine equivalents.

3. The composition of claim 2, wherein the composition comprises chondroitin, butyric acid, trehalose and spermidine.

4. The composition of claim 1, wherein the composition comprises (i) collagen peptides and (ii) at least one substance selected from the group consisting of butyric acid, butyric acid equivalents, trehalose, trehalose equivalents, spermidine, and spermidine equivalents.

5. The composition of claim 4, wherein the composition comprises collagen peptides, butyric acid, trehalose and spermidine.

6. The composition of claim 1, wherein the composition comprises (i) chondroitin, (ii) collagen peptide and (iii) at least one substance selected from butyric acid, butyric acid equivalents, trehalose, trehalose equivalents, spermidine and spermidine equivalents.

7. The composition of any one of claims 1, 2, 4 and 6, wherein the trehalose equivalent is mannitol, glucosamine, acetylglucosamine, galactosamine, mannosamine, glycerol, erythritol or xylitol.

8. The composition of any one of claims 1, 2, 4 and 6, wherein the spermidine equivalent is putrescine, spermine, norspermidine, acetylspermidine, diacetylspermidine, methylated spermidine, methylated polyamines or spermidine salts.

9. The composition of any one of claims 1, 2, 4, and 6, wherein the butyrate equivalent is acetic acid.

10. The composition of claim 6, wherein the composition comprises chondroitin, collagen peptides, butyric acid, trehalose, and spermidine.

11. The composition of claim 10, wherein the composition comprises 50 mg to 6,000 mg chondroitin, 50 mg to 20,000 mg collagen peptides, 50 mg to 12,000 mg butyric acid, 0.1 g to 50 g trehalose, and 0.1 mg to 30 mg spermidine.

12. The composition of claim 11, wherein the composition comprises 1,200 mg chondroitin, 5,000 mg collagen peptides, 1,100 mg butyric acid, 10 g trehalose, and 2 mg spermidine.

13. The composition of claim 10, wherein the composition comprises (i) chondroitin, collagen peptides, butyric acid, trehalose, and spermidine, and (ii) one or more substances selected from the group consisting of ascorbic acid or ascorbic acid equivalents, α-ketoglutaric acid or α-ketoglutaric acid equivalents, pomegranate or pomegranate equivalents, phospholipids, B vitamins, and apigenin or apigenin equivalents.

14. The composition of claim 13, wherein the composition comprises chondroitin, collagen peptides, butyric acid, trehalose, spermidine, ascorbic acid, and alpha-ketoglutarate.

15. The composition of claim 13, wherein the composition comprises chondroitin, collagen peptides, butyric acid, trehalose, spermidine, ascorbic acid, alpha-ketoglutaric acid, and phosphatidylcholine.

16. The composition of claim 10, wherein the composition comprises chondroitin, collagen peptides, butyric acid, trehalose, spermidine, ascorbic acid, alpha-ketoglutaric acid, phosphatidylcholine, and B vitamins.

17. The composition of claim 10, wherein the composition comprises chondroitin, collagen peptides, butyric acid, trehalose, spermidine, ascorbic acid, alpha-ketoglutaric acid, phosphatidylcholine, B vitamins, and apigenin or an apigenin equivalent.

18. The composition of claim 13, wherein the composition comprises 400 mg to 1,200 mg chondroitin, 1,000 mg to 5,000 mg collagen peptides, 400 mg to 1,200 mg butyric acid, 1 g to 20 g trehalose, 0.2 mg to 20 mg spermidine, 500 mg ascorbic acid, 500 mg to 4,000 mg alpha-ketoglutaric acid, 100 mg to 3,000 mg pomegranate or pomegranate equivalent, 250 mg to 2,400 mg phosphatidylcholine, 100% to 300% of the U.S. Recommended Daily Allowance of B vitamins, and 50 mg apigenin.

19. The composition of claim 18, wherein the composition comprises 1,200 mg chondroitin, 5,000 mg collagen peptides, 1,100 mg butyric acid, 10 g trehalose, 2 mg spermidine, 500 mg ascorbic acid, 1,100 mg alpha-ketoglutaric acid, 1,500 mg pomegranate or pomegranate equivalent, 1,200 mg phosphatidylcholine, 200% of the U.S. Recommended Daily Allowance of B vitamins, and 50 mg apigenin.

20. The composition of any one of claims 1 to 19, wherein one or more of the substances in the composition are formulated for delayed release and / or extended release.

21. A composition comprising (i) the composition of any one of claims 1 to 20 and (ii) a pharmaceutically acceptable carrier.

22. The composition of any one of claims 1 to 21, wherein the composition is in a form selected from a food, a nutritional supplement, a nutraceutical, and a skin care product.

23. A method for ameliorating at least one characteristic of aging in a subject, comprising administering to the subject the composition of any one of claims 1 to 22, wherein the characteristic of aging is selected from genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, transcriptome dysregulation, cross-linking, and altered intercellular communication.

24. The method of claim 23, wherein the method ameliorates genomic instability, loss of proteostasis, one or more epigenetic alterations, telomere attrition, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, transcriptome dysregulation, cross-linking, and altered intercellular communication.

25. The method of claim 23 or 24, wherein the subject is a human.

26. The method of claim 23 or 24, wherein the subject is a rodent, rabbit, cat, dog, or horse.

27. An article comprising, in separate compartments, (i) the composition of any one of claims 1, 2, 4, and 6 to 9, wherein the composition does not contain butyric acid or a butyric acid equivalent, and (ii) butyric acid and / or a butyric acid equivalent.

28. An article comprising the composition of any one of claims 3, 5, and 10 to 22, wherein (i) the butyric acid and / or butyric acid equivalents and (ii) other components of the composition are located in separate compartments.