Use of active ingredients for treating and / or preventing skin senescence

Abstract

A composition may include a cosmetic use of an active agent for treating and / or preventing skin senescence, wherein the agent is capable of inhibiting the senescence -associated secretory phenotype by i) mitigating release of IL-6, IL-8, TNF-oc and MMP1 (matrix metallopeptidase- 1); ii) reducing activity of b-galactosidase; iii) reducing secreted frizzled-related protein 4 (SFRP 4) biosynthesis; and iv) reducing expression of p21 in fibroblasts.

Description

[0001] USE OF ACTIVE INGREDIENTS FOR TREATING AND / OR PREVENTING SKIN SENESCENCE

[0002] CLAIM OF PRIORITY

[0003] [1] This patent application claims the benefit of priority to U.S. Provisional Application Serial No. 63 / 500,417, filed May 5, 2023; U.S. Provisional Application Serial No. 63 / 626,823, filed January 30, 2024; and French Application Serial No. 2313018, filed November 24, 2023, which are incorporated by reference herein in their entireties.

[0004] BACKGROUND

[0005] [2] The invention is generally directed to active ingredients capable of countering dermal intrinsic ageing and its manifestations, compositions containing them and their use as cosmetic or medical (e g. dermatological) dermal compositions.

[0006] [3] Skin is the largest organ of the human body: it provides a barrier against harmful organisms and substances, protects against UV radiation and regulates water loss and body temperature. The skin is a complex organ, consisting of several compartments with different functions. The outermost epidermis is stratified into four sublayers (basal, spinous, granular and cornified layer) with keratinocytes being the predominant cell type. Pigment-producing melanocytes reside within the basal layer of the epidermis, determine skin color and possess photo-protecting properties. The dermal-epidermal junction (DEJ) connects the epidermis to the underlying dermis, which harbors dermal fibroblasts and appendages such as hair follicles, sebaceous glands, and sweat glands (1).

[0007] [4] Skin aging is a multi-factorial process that affects nearly every aspect of its biology and function; it is driven by both intrinsic (e.g., time, genetic factors, hormones) and extrinsic (e.g., UV exposure, pollution) factors. The apparent signs of intrinsic ageing include the loss and descent of underlying fat, leading to hollowed cheeks and eye sockets, as well as loss of firmness and sagging skin as the bones shrink away from the skin due to bone loss. Other visible signs include thin and dry skin, fine wrinkles, decreased elasticity, aberrant pigmentation, hair graying and hair loss.

[0008] [5] Intrinsic and extrinsic aging are partly due to the process of senescence and represent an inevitable change attributable to the passage of time alone and is represented primarily by physiologic alterations with subtle but undoubtedly important consequences for

[0009] 1

[0010] SUBSTITUTE SHEET (RULE 26) both healthy and diseased skin and is largely genetically determined. Senescence, and in particular skin senescence, is a continuous process that usually begins in the mid-20s but may not become evident for decades. In a person’s 20s collagen production begins to slow and elastin has a bit less spring. Dead skin cells do not shed as quickly, and turnover of new skin cells decreases. The process of intrinsic skin aging resembles that seen in most internal organs and an explanation is thought to involve decreased proliferative capacity leading to cellular senescence, and altered biosynthetic activity of skin derived cells The intrinsic rate of skin aging in any individual can be dramatically influenced by personal and environmental factors, particularly the amount of exposure to ultraviolet light. For example, photodamage, which considerably accelerates the visible aging of skin, also greatly increases the risk of cutaneous neoplasms: the processes of intrinsic and extrinsic aging are superimposed. It is essential to stress however that the terms aging and cellular senescence cannot be used interchangeably: aging is a progressive decline with time whereas senescence occurs throughout the lifespan, including during embryogenesis. The number of senescent cells increases with age, but senescence also plays an important role during development (2).

[0011] [6] Senescence does not occur only in the skin. Its role in all tissues is to prevent the replication of cells harboring damaged DNA, which serves an important anti-tumorigenic function. Senescence typically occurs in response to damaging stimuli, including telomere shortening (replicative senescence), DNA damage (DNA damage-induced senescence), and oncogenic signaling (oncogene-induced senescence).

[0012] [7] Replicative senescence refers to the phenomenon whereby normal nonmalignant cells stop dividing in vitro, after approximately fifty divisions, which has been termed the Hayflick limit. Replicative senescence is induced by telomere shortening. With each round of DNA replication, telomeres are progressively shortened, eventually reaching a critical length which prevents further replication, thereby halting cell division. Critically short, uncapped telomeres initiate a DNA damage response which triggers senescence.

[0013] [8] DNA damage triggers the DNA repair machinery, apoptosis, or senescence depending on the extent of damage and physiological context. Senescent cells are characterized by a persistent DNA damage response (DDR), including chronic ATM (Ataxia Telangiectasia mutated) and ATR (Ataxia Telangiectasia and Rad3 related) kinase signaling which ultimately invokes cell cycle arrest and senescence through activation of the p53 / p21 and pl6 / pRb

[0014] 2

[0015] SUBSTITUTE SHEET (RULE 26) pathways. Persistent DNA damage and subsequent senescence can also be induced by ionizing radiation, chemotherapeutics, genotoxic stress, and oxidative stress.

[0016] [9] Cellular senescence is induced in response to oncogenic signaling as a potent cell autonomous anti-cancer mechanism. Senescence occurring in cells with oncogenic signaling is a response intended to prevent their transformation to malignant cells. Oncogene- induced senescence (OIS) results from the hyperactivation of oncogenes like H-Ras or the inactivation of tumor suppressors such as PTEN. For example, expression of H-RASV12, an oncogenic form of the GTPase H-RAS, triggers OIS by inducing chronic p38 mitogen- activated protein kinase (p38 MAPK) signaling. Strong mitogenic signaling can also induce DNA damage via replication stress which triggers the collapse of stalled replication forks (2).

[0017]

[0010] Senescent cells are characterized by stable cell cycle arrest as well as morphological and metabolic changes, chromatin reorganization, altered gene expression, and acquisition of the senescence-associated secretory phenotype (SASP). One important property of senescent cells is that they can also contaminate healthy cells, turning them into senescent cells too, and then accelerating their ageing. The new senescent cells adopt the same communication patterns with healthy cells, and the vicious cycle continues. Left unchecked, these cells can increase by up to three times after 65 years old.

[0018]

[0011] Applied to the skin, this knowledge might reverse the concept of inside out beauty suggesting that the skin, our largest organ, could have an impact on how we age overall. It might be a whole new way to look at skin healthy longevity.

[0019]

[0012] As mentioned above, the hallmark of senescent cells is the appearance of the senescence-associated secretory phenotype (SASP). The SASP includes several families of soluble and insoluble factors that can be globally divided into the following major categories: soluble signaling factors (interleukins, chemokines, and growth factors), secreted proteases and secreted insoluble proteins / extracellular matrix (ECM) components (4).

[0020]

[0013] Because of their potential involvement in many aging and disease processes, eliminating senescent cells and attenuating the senescence-associated secretory phenotype (SASP) have emerged as attractive therapeutic and cosmetic strategies; however, translation of these findings into relevant human applications is currently limited by the fragmentary understanding of both the basic molecular cell biology of in vivo senescent cells and the overall importance of senescence to age-related diseases (3).

[0021] 3

[0022] SUBSTITUTE SHEET (RULE 26)

[0014] Known SASP inhibitors belong to one of the following pharmacological categories: a. Glucocorticoids as potent suppressors of selected components of the SASP; b. Statins such as simvastatin, that can reduce the expression of pro- inflammatory cytokines (IL-6, IL-8, and MCP-1); c. JAK1 / 2 inhibitors such as ruxolitinib; d. NF-KB and p38 inhibitors; e. Mitochondrial depleters in the case of impaired mitophagy

[0023]

[0015] There is however the need to develop new SASP inhibitors to meet the desire to shift dermatological focus from ameliorating the cosmetic consequences of skin aging to decreasing the genuine morbidity associated with problems of the aging skin in the face of an ageing population.

[0024]

[0016] There is also the need to develop new SASP inhibitors to selectively eliminate senescent cells in vivo, thereby reducing inflammation, enhancing immune system function, slowing the progression of age-related diseases, all of which would lead to increased health and lifespan.

[0025]

[0017] W02023 / 012115 discloses an active ingredient comprising at least one extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-P- glucans with a molar mass of between 2 and 5 kDa. Preferably, said extract consists of the cytosolic fraction of a Saccharomyces cerevisiae yeast (INCL Saccharomyces cerevisiae Extract). Said ingredient is proposed for use in ameliorating skin regeneration and in treating skin ageing, in particular wrinkles, dark circles and the radiance of the complexion. It is described as being able to improve the interplay of the cutaneous, vascular and immune systems by increasing the synthesis and secretion of the growth factors (KGF, EGF, IGF, FGF, PDGF, TGF-p and VEGF).

[0026] SUMMARY OF THE INVENTION

[0027]

[0018] The present invention provides an active ingredient capable of inhibiting the senescence -associated secretory phenotype by inhibiting or reducing i) release of IL-6, IL-8, TNF-a and MMP1 (matrix metallopeptidase-1); ii) activity of P-galactosidase; iii) secreted frizzled-related protein 4 (SFRP 4) biosynthesis; and iv) expression of p21 in fibroblasts.

[0028] 4

[0029] SUBSTITUTE SHEET (RULE 26) Specifically, the active ingredient comprises at least one extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo- - glucans with a molar mass of between 2 and 5 kDa, preferably in combination with adenosine and / or Schisandra Sphenanthera Fruit Extract.

[0030]

[0019] Reduction in the sense of the present invention means preferably at least about minus 20%, about minus 25%, about minus 30%, about minus 35%, about minus 40%, about minus 45%, about minus 50%, about minus 55%, about minus 60%, about minus 65%, about minus 70%, about minus 75%, about minus 80%, about minus 85%, about minus 90%, about minus 95% compared to the level of the respective marker in non-treated senescent cells. All the ranges laying between any pair of the values above are hereby explicitly disclosed.

[0031]

[0020] By inhibiting the senescence -associated secretory phenotype, the ingredient treats the apparent signs of intrinsic skin ageing like hollowed cheeks and eye sockets; loss of skin firmness; sagging, thin and dry skin; fine wrinkles; decreased elasticity; aberrant pigmentation; and hair graying and loss.

[0032]

[0021] The present invention also provides the cosmetic use of an extract of Saccharomyces cerevisiae for treating and / or preventing skin senescence, said extract corresponding to the cytosolic fraction comprising oligo- - glucans with a molar mass of between 2 and 5 kDa, particularly wherein skin senescence comprises the apparent signs of intrinsic skin ageing like hollowed cheeks and eye sockets; loss of skin firmness; sagging, thin and dry skin; fine wrinkles; decreased elasticity; aberrant pigmentation; and hair graying and loss.

[0033]

[0022] The present invention also provides the cosmetic use of a composition comprising an extract of of Saccharomyces cerevisiae for treating and / or preventing skin senescence, said extract corresponding to the cytosolic fraction comprising oligo- - glucans with a molar mass of between 2 and 5 kDa for treating and / or preventing skin senescence.

[0034]

[0023] The present invention also provides a therapeutically effective amount of an extract of Saccharomyces cerevisiae for use in treating and / or preventing senescence, said extract corresponding to the cytosolic fraction comprising oligo- - glucans with a molar mass of between 2 and 5 kDa, in particular wherein senescence can be in particular replicative senescence, DNA-damage induced senescence or oncogene-induced senescence. More particularly senescence can be skin senescence, e.g. the apparent signs of intrinsic skin ageing.

[0035] 5

[0036] SUBSTITUTE SHEET (RULE 26)

[0024] The present invention also provides a therapeutically effective amount of an extract of Saccharomyces cerevisiae for use in treating and / or preventing age-associated diseases in humans, said extract corresponding to the cytosolic fraction comprising oligo- - glucans with a molar mass of between 2 and 5 kDa. The age-associated disease can in particular be cancer, heart disease or dementia.

[0037]

[0025] According to the present invention, the composition can be for topical application, in particular in the form of an oil-in-water emulsion, a water-in-oil emulsion, a multiple emulsion (Water / Oil / Water or Oil / Water / Oil), a microemulsion, a nanoemulsion, a solution, a suspension, a hydrodispersion, a gel, an ointment, a paste, an aerosol foam, a spray, an aqueous gel, a powder, a foundation, a transdermal patch, a cream or a mask.

[0038]

[0026] The composition can also be suitable for enteral or parenteral administration, in particular intradermal or subcutaneous administration.

[0039]

[0027] According to the present invention, the extract can be present in a cosmetically or pharmaceutically useful amount. For example, a cosmetic or therapeutic composition comprises at least 0.00025% by weight, preferably between 0.001% and 2%, more preferably between 0.01% and 1%, even more preferably between 0.025% and 0.5%, even more preferably between 0.05% and 0.1%, most preferably 0.0625% by weight of the whole composition.

[0040] BRIEF DESCRIPTION OF THE FIGURES

[0041]

[0028] In the drawings, which are not necessarily drawn to scale, like numerals describe substantially similar components throughout the several views. The drawings illustrate generally, by way of example, but not by way of limitation, various aspects of the present invention.

[0042]

[0029] FIGS. 1A to 1C are summaries of Senescence-Associated IL6, IL8, and TNFoc release in the presence or absence of an active ingredient comprising oligo-0- glucans derived from the cytosolic fraction of Saccharomyces cerevisiae.

[0043]

[0030] FIG. 2 is a summary of expression of a SASP-associated matrix metalloproteinase, MMP1, in the presence or absence of an active ingredient comprising oligo- P- glucans derived from the cytosolic fraction of Saccharomyces cerevisiae.

[0044] 6

[0045] SUBSTITUTE SHEET (RULE 26)

[0031] FIG 3 is a summary of Senescence-Associated P-galactosidase activity in the presence or absence of an active ingredient comprising oligo-P- glucans derived from the cytosolic fraction of Saccharomyces cerevisiae.

[0046]

[0032] FIG 4 is a summary of SFRP4 (secreted frizzled-related protein 4) immunostaining in the presence or absence of an active ingredient comprising oligo-P- glucans derived from the cytosolic fraction of Saccharomyces cerevisiae.

[0047] DETAILED DESCRIPTION OF THE INVENTION

[0048]

[0033] Reference will now be made in detail to certain aspects of the disclosed subject matter, examples of which are illustrated in part in the accompanying drawings. While the disclosed subject matter will be described in conjunction with the enumerated claims, it will be understood that the exemplified subject matter is not intended to limit the claims to the disclosed subject matter.

[0049]

[0034] Throughout this document, values expressed in a range format should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. For example, a range of “about 0.1% to about 5%” or “about 0.1% to 5%” should be interpreted to include not just about 0.1% to about 5%, but also the individual values (e.g., 1%, 2%, 3%, and 4%) and the sub-ranges (e.g., 0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%) within the indicated range. The statement “about X to Y” has the same meaning as “about X to about Y,” unless indicated otherwise. Likewise, the statement “about X, Y, or about Z” has the same meaning as “about X, about Y, or about Z,” unless indicated otherwise.

[0050]

[0035] In this document, the terms “a,” “an,” or “the” are used to include one or more than one unless the context clearly dictates otherwise. The term “or” is used to refer to a nonexclusive “or” unless otherwise indicated. The statement “at least one of A and B” or “at least one of A or B” has the same meaning as “A, B, or A and B.” In addition, it is to be understood that the phraseology or terminology employed herein, and not otherwise defined, is for the purpose of description only and not of limitation. Any use of section headings is intended to aid reading of the document and is not to be interpreted as limiting; information that is relevant to a section heading may occur within or outside of that particular section. A comma can be used as a delimiter or digit group separator to the left or right of a decimal mark;

[0051] 7

[0052] SUBSTITUTE SHEET (RULE 26) for example, “0.000,1” is equivalent to “0.0001.” All publications, patents, and patent documents referred to in this document are incorporated by reference herein in their entirety, as though individually incorporated by reference In the event of inconsistent usages between this document and those documents so incorporated by reference, the usage in the incorporated reference should be considered supplementary to that of this document; for irreconcilable inconsistencies, the usage in this document controls

[0053]

[0036] The term “about” as used herein can allow for a degree of variability in a value or range, for example, within 10%, within 5%, or within 1% of a stated value or of a stated limit of a range and includes the exact stated value or range. The term “substantially” as used herein refers to a majority of, or mostly, as in at least about 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, 99.99%, or at least about 99.999% or more, or 100%. The term “substantially free of’ as used herein can mean having none or having a trivial amount of, such that the amount of material present does not affect the material properties of the composition including the material, such that about 0 wt% to about 5 wt% of the composition is the material, or about 0 wt% to about 1 wt%, or about 5 wt% or less, or less than or equal to about 4.5 wt%, 4, 3.5, 3, 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.01, or about 0.001 wt% or less, or about 0 wt%.

[0054]

[0037] When percentages of ingredients in compositions are indicated, the standard error applies. For example, 3.0% is to be interpreted as 2.9% to 3.1%.

[0055]

[0038] The term “comprises” and variations thereof is to be interpreted as meaning both “includes”, “substantially consists of and “consists of, and variations thereof.

[0056]

[0039] The present invention provides an active ingredient capable of inhibiting the senescence -associated secretory phenotype by mitigating release of IL-6, IL-8, TNF-oi and MMP1 (matrix metallopeptidase-1). Specifically, the active ingredient comprises at least one extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo- - glucans with a molar mass of between 2 and 5 kDa.

[0057]

[0040] The present invention also provides a cosmetic use of at least one extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-P- glucans with a molar mass of between 2 and 5 kDa for treating and / or preventing skin senescence. The extract may be present in a cosmetically effective amount.

[0058]

[0041] In particular, the present invention provides a cosmetic use of at least one extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising

[0059] 8

[0060] SUBSTITUTE SHEET (RULE 26) oligo-P- glucans with a molar mass of between 2 and 5 kDa for treating and / or preventing the apparent signs of intrinsic skin ageing like hollowed cheeks and eye sockets; loss of skin firmness; sagging, thin and dry skin; fine wrinkles; decreased elasticity; aberrant pigmentation; and hair graying and loss. The extract may be present in a cosmetically effective amount.

[0061]

[0042] The present invention also provides a therapeutically effective amount of an active agent comprising at least one extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-P- glucans with a molar mass of between 2 and 5 kDa, for use in treating and / or preventing skin senescence. The extract may be present in a pharmaceutically effective amount.

[0062]

[0043] In particular, the present invention provides a therapeutically effective amount of an active agent comprising at least one extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-P- glucans with a molar mass of between 2 and 5 kDa, for use in treating and / or preventing the apparent signs of intrinsic skin ageing like hollowed cheeks and eye sockets; loss of skin firmness; sagging, thin and dry skin; fine wrinkles; decreased elasticity; aberrant pigmentation; and hair graying and loss.

[0063]

[0044] The present invention also provides a cosmetic use of a composition comprising at least one extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-P- glucans with a molar mass of between 2 and 5 kDa, for treating and / or preventing skin senescence. The extract may be present in the composition in a cosmetically effective amount.

[0064]

[0045] In particular, the present invention provides a cosmetic use of a composition comprising at least one extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-P- glucans with a molar mass of between 2 and 5 kDa for treating and / or preventing the apparent signs of intrinsic skin ageing like hollowed cheeks and eye sockets; loss of skin firmness; sagging, thin and dry skin; fine wrinkles; decreased elasticity; aberrant pigmentation; and hair graying and loss. The extract may be present in the composition in a cosmetically effective amount.

[0065]

[0046] The present invention also provides a therapeutically effective amount of a composition comprising at least one extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-P- glucans with a molar mass of between 2 and 5 kDa, for use in treating and / or preventing skin senescence. The extract may be present in the composition in a pharmaceutically effective amount.

[0066] 9

[0067] SUBSTITUTE SHEET (RULE 26)

[0047] In particular, the present invention provides a therapeutically effective amount of a composition comprising at least one extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo- - glucans with a molar mass of between 2 and 5 kDa, for treating and / or preventing the apparent signs of intrinsic skin ageing like hollowed cheeks and eye sockets; loss of skin firmness; sagging, thin and dry skin; fine wrinkles; decreased elasticity; aberrant pigmentation; and hair graying and loss. The extract may be present in the composition in a pharmaceutically effective amount.

[0068]

[0048] According to the present invention, the extract can be present in a cosmetically or pharmaceutically useful amount For example, a cosmetic or therapeutic composition comprises at least 0.00025% by weight, preferably between 0.001% and 2%, more preferably between 0.01% and 1%, even more preferably between 0.025% and 0.5%, even more preferably between 0.05% and 0.1%, most preferably 0.0625% by weight of the whole composition.

[0069]

[0049] The compositions of the present invention may comprise other agents active to treat or prevent senescence, in particular adenosine and / or Schisandra Sphenanthera Fruit Extract (INCI). The extract of Saccharomyces cerevisiae corresponding to the cytosolic fraction comprising oligo-P- glucans with a molar mass of between 2 and 5 kDa together with adenosine and / or Schisandra Sphenanthera Fruit Extract may give rise to a synergistic effect in the cosmetic and / or therapeutic treatments of the present invention.

[0070]

[0050] The topical compositions according to the invention may comprise at least one further ingredient commonly found in topical cosmetic and / or medical (e.g. dermatological) compositions chosen from water, oils, which may be chosen in particular from volatile and / or non-volatile, linear or cyclic silicone oils, waxes (such as ozokerite, polyethylene wax, beeswax or carnauba wax), silicone elastomers, nonionic, anionic, cationic and / or amphoteric surfactants, co-surfactant (such as linear fatty alcohols), thickeners, gelling agents, humectants (such as polyols like glycerin), colorants, preservatives, fillers, tensors, sequestrants, perfumes, and mixtures hereof.

[0071]

[0051] These compositions can be in particular in the form of oil-in-water emulsions, water-in-oil emulsions, multiple emulsions (Water / Oil / Water or Oil / Water / Oil) which can optionally be microemulsions or nanoemulsions, or in the form of solutions, suspensions, hydrodispersions, gels, ointments, pastes, aerosol foams or sprays, aqueous gels, powders, or foundations or transdermal patches. They can be more or less fluid and have the appearance of

[0072] 10

[0073] SUBSTITUTE SHEET (RULE 26) creams, emulsions, gels, masks or any other aspect of healthy skin care cosmetics. The person skilled in the art is aware of the procedures, ingredients and forms of common use in the preparation of dermal formulations.

[0074]

[0052] A “gel” is a colloid in which the dispersed phase has combined with the continuous phase to produce a semisolid material, such as jelly.

[0075]

[0053] An “oil” is a composition containing at least 95% wt of a lipophilic substance. Examples of lipophilic substances include but are not limited to naturally occurring and synthetic oils, fats, fatty acids, lecithins, triglycerides and combinations thereof.

[0076]

[0054] A “continuous phase” refers to the liquid in which solids are suspended or droplets of another liquid are dispersed and is sometimes called the external phase. This also refers to the fluid phase of a colloid within which solid or fluid particles are distributed. If the continuous phase is water (or another hydrophilic solvent), water-soluble or hydrophilic drugs will dissolve in the continuous phase (as opposed to being dispersed). In a multiphase formulation (e.g., an emulsion), the discreet phase is suspended or dispersed in the continuous phase. Excipients for topical administration may include anti-microbial compounds, e.g. parabens, antioxidants, e g. sodium ascorbyl acetate and alpha-tocopherol, stabilizers, e.g. sorbitol, and / or emulsifying agents to produce a stable emulsion with both a hydrophilic and a hydrophobic phase.

[0077]

[0055] ‘Diluents” may be included in the formulations to dissolve, disperse or otherwise incorporate the carrier. Examples of diluents include, but are not limited to, water, buffered aqueous solutions, organic hydrophilic diluents, such as monovalent alcohols, and low molecular weight glycols and polyols (e.g. propylene glycol, polypropylene glycol, glycerol, butylene glycol).

[0078]

[0056] Appropriate excipients are selected based on the type of formulation. Standard excipients include gelatin, casein, lecithin, gum acacia, cholesterol, tragacanth, stearic acid, benzalkonium chloride, calcium stearate, glyceryl monostearate, cetostearyl alcohol, cetomacrogol emulsifying wax, sorbitan esters, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyethylene glycols, polyoxyethylene stearates, colloidol silicon dioxide, phosphates, sodium dodecyl sulfate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethycellulose phthalate,

[0079] 11

[0080] SUBSTITUTE SHEET (RULE 26) noncrystalline cellulose, magnesium aluminum silicate, triethanolamine, polyvinyl alcohol, polyvinylpyrrolidone, sugars, and starches.

[0081]

[0057] An emulsion is a preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. The oil phase may consist at least in part of a propellant, such as an HFA propellant Either or both of the oil phase and the aqueous phase may contain one or more surfactants, emulsifiers, emulsion stabilizers, buffers, and other excipients. Preferred excipients include surfactants, especially non-ionic surfactants; emulsifying agents, especially emulsifying waxes; and liquid non-volatile non-aqueous materials, particularly glycols such as propylene glycol. The oil phase may contain other oily pharmaceutically approved excipients. For example, materials such as hydroxylated castor oil or sesame oil may be used in the oil phase as surfactants or emulsifiers.

[0082]

[0058] ‘Emollients” are an externally applied agent that softens or soothes skin and are generally known in the art and listed in compendia, such as the “Handbook of Pharmaceutical Excipients”, 4thEd., Pharmaceutical Press, 2003. These include, without limitation, almond oil, castor oil, ceratonia extract, cetostearoyl alcohol, cetyl alcohol, cetyl esters wax, cholesterol, cottonseed oil, cyclomethicone, ethylene glycol palmitostearate, glycerin, glycerin monostearate, glyceryl monooleate, isopropyl myristate, isopropyl palmitate, lanolin, lecithin, light mineral oil, medium-chain triglycerides, mineral oil and lanolin alcohols, petrolatum, petrolatum and lanolin alcohols, soybean oil, starch, stearyl alcohol, sunflower oil, xylitol and combinations thereof. In one embodiment, the emollients are ethylhexyl stearate and ethylhexyl palmitate.

[0083]

[0059] Surfactants” are surface-active agents that lower surface tension and thereby increase the emulsifying, foaming, dispersing, spreading and wetting properties of a product. Suitable non-ionic surfactants include emulsifying wax, glyceryl monooleate, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polysorbate, sorbitan esters, benzyl alcohol, benzyl benzoate, cyclodextrins, glycerin monostearate, poloxamer, povidone and combinations thereof. In one embodiment, the non-ionic surfactant is stearyl alcohol.

[0084] 12

[0085] SUBSTITUTE SHEET (RULE 26)

[0060] ‘Emulsifiers” are surface active substances which promote the suspension of one liquid in another and promote the formation of a stable mixture, or emulsion, of oil and water. Common emulsifiers are: metallic soaps, certain animal and vegetable oils, and various polar compounds. Suitable emulsifiers include acacia, anionic emulsifying wax, calcium stearate, carbomers, cetostearyl alcohol, cetyl alcohol, cholesterol, diethanolamine, ethylene glycol palmitostearate, glycerin monostearate, glyceryl monooleate, hydroxpropyl cellulose, hypromellose, lanolin, hydrous, lanolin alcohols, lecithin, medium-chain triglycerides, methylcellulose, mineral oil and lanolin alcohols, monobasic sodium phosphate, monoethanolamine, nonionic emulsifying wax, oleic acid, poloxamer, poloxamers, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, propylene glycol alginate, self-emulsifying glyceryl monostearate, sodium citrate dehydrate, sodium lauryl sulfate, sorbitan esters, stearic acid, sunflower oil, tragacanth, triethanolamine, xanthan gum and combinations thereof. In one embodiment, the emulsifier is glycerol stearate.

[0086]

[0061] A “lotion” is a low- to medium-viscosity liquid formulation. A lotion can contain finely powdered substances that are in soluble in the dispersion medium through the use of suspending agents and dispersing agents. Alternatively, lotions can have as the dispersed phase liquid substances that are immiscible with the vehicle and are usually dispersed by means of emulsifying agents or other suitable stabilizers. In one embodiment, the lotion is in the form of an emulsion having a viscosity of between 100 and 1000 centistokes. The fluidity of lotions permits rapid and uniform application over a wide surface area. Lotions are typically intended to dry on the skin leaving a thin coat of their medicinal components on the skin's surface.

[0087]

[0062] A “cream” is a viscous liquid or semi-solid emulsion of either the “oil-in-water” or “water-in-oil type”. Creams may contain emulsifying agents and / or other stabilizing agents. In one embodiment, the formulation is in the form of a cream having a viscosity of greater than 1000 centistokes, typically in the range of 20,000-50,000 centistokes. Creams are often time preferred over ointments as they are generally easier to spread and easier to remove.

[0088]

[0063] An “ointment” is a semisolid preparation containing an ointment base and optionally one or more active agents. Examples of suitable ointment bases include hydrocarbon bases (e.g., petrolatum, white petrolatum, yellow ointment, and mineral oil); absorption bases (hydrophilic petrolatum, anhydrous lanolin, lanolin, and cold cream); water-removable bases (e.g., hydrophilic ointment), and water-soluble bases (e.g., polyethylene glycol ointments).

[0089] 13

[0090] SUBSTITUTE SHEET (RULE 26) Pastes typically differ from ointments in that they contain a larger percentage of solids. Pastes are typically more absorptive and less greasy that ointments prepared with the same components.

[0091]

[0064] A “gel” is a semisolid system containing dispersions of small or large molecules in a liquid vehicle that is rendered semisolid by the action of a thickening agent or polymeric material dissolved or suspended in the liquid vehicle. The liquid may include a lipophilic component, an aqueous component or both. Some emulsions may be gels or otherwise include a gel component. Some gels, however, are not emulsions because they do not contain a homogenized blend of immiscible components. Suitable gelling agents include, but are not limited to, modified celluloses, such as hydroxypropyl cellulose and hydroxyethyl cellulose; Carbopol homopolymers and copolymers; and combinations thereof. Suitable solvents in the liquid vehicle include, but are not limited to, diglycol monoethyl ether; alklene glycols, such as propylene glycol; dimethyl isosorbide; alcohols, such as isopropyl alcohol and ethanol. The solvents are typically selected for their ability to dissolve the drug. Other additives, which improve the skin feel and / or emolliency of the formulation, may also be incorporated. Examples of such additives include, but are not limited, isopropyl myristate, ethyl acetate, C12- C15 alkyl benzoates, mineral oil, squalane, cyclomethicone, capric / caprylic triglycerides, and combinations thereof.

[0092]

[0065] ‘Foams” consist of an emulsion in combination with a gaseous propellant. The gaseous propellant consists primarily of hydrofluoroalkanes (HF As). Suitable propellants include HFAs such as 1 , 1 , 1 ,2-tetrafluoroethane (HFA 134a) and 1, 1,1, 2, 3,3,3- heptafluoropropane (HFA 227), but mixtures and admixtures of these and other HFAs that are currently approved or may become approved for medical use are suitable. The propellants preferably are not hydrocarbon propellant gases which can produce flammable or explosive vapors during spraying. Furthermore, the compositions preferably contain no volatile alcohols, which can produce flammable or explosive vapors during use.

[0093]

[0066] Buffers are used to control pH of a composition. Preferably, the buffers buffer the composition from a pH of about 4 to a pH of about 7.5, more preferably from a pH of about 4 to a pH of about 7, and most preferably from a pH of about 5 to a pH of about 7. In a preferred embodiment, the buffer is based on triethanolamine, citric acid, sodium hydroxyde, disodium phosphate and potassium phosphate.

[0094] 14

[0095] SUBSTITUTE SHEET (RULE 26)

[0067] Preservatives can be used to prevent the growth of fungi and microorganisms. Suitable antifungal and antimicrobial agents include, but are not limited to, benzoic acid, butylparaben, ethyl paraben, methyl paraben, propylparaben, sodium benzoate, sodium propionate, benzalkonium chloride, benzethonium chloride, benzyl alcohol, cetylpyridinium chloride, chlorobutanol, phenol, phenylethyl alcohol, potassium sorbate, caprylyl alcohol, 1,2- hexandiol, and thimerosal.

[0096]

[0068] Antioxidants can be used in the compositions of the present invention. Examples of antioxidants are tocopherol, hydroxyacetophenone, dimethylmethoxy chromanol and phenethyl alcohol.

[0097]

[0069] Viscosity modifiers can additionally be present, such as potassium chloride and natural gums such as xanthan gum, gum arabic, gum tragacanth, carrageenan, chitosan, guar gum, konjac gum, sclerotium gum, dextrins and starch.

[0098]

[0070] Chelating agents may additionally be present, such as sodium glucuronate.

[0099]

[0071] Fragrances may be added to the compositions of the invention.

[0100]

[0072] Penetration enhancers are frequently used to promote transdermal delivery of drugs across the skin, in particular across the stratum corneum. The more commonly used enhancers include urea, (carbonyldiamide), imidurea, N, N-diethylformamide, N-methyl-2- pyrrolidine, 1 -dodecal -azacy cl opheptane-2-one, calcium thioglycate, 2-pyyrolidine, N,N- diethyl-m-toluamide, oleic acid and its ester derivatives, such as methyl, ethyl, propyl, isopropyl, butyl, vinyl and glycerylmonooleate, sorbitan esters, such as sorbitan monolaurate and sorbitan monooleate, other fatty acid esters such as isopropyl laurate, isopropyl myristate, isopropyl palmitate, diisopropyl adipate, propylene glycol monolaurate, propylene glycol monooleatea and non-ionic detergents such as BRIJ® 76 (stearyl poly(10 oxy ethylene ether), BRU® 78 (stearyl poly(20)oxyethylene ether), BRU® 96 (oleyl poly(10)oxy ethylene ether), and BRU® 721 (stearyl poly (21) oxyethylene ether) (ICI Americas Inc. Corp.).

[0101]

[0073] Emulsion stabilizers, surfactants and emulsifying agents may additionally be present, such as sorbitan isostearate, hydroxyethyl acrylate / sodium acryloxydiethyl taurate copolymer and sorbitan isostearate.

[0102]

[0074] Humectants are crucial in skincare by providing essential skin hydration and maintaining the skin's moisture balance. Exemplary humectant are Glycerin, Hyaluronic acid, Aloe vera, Honey, Hydrolyzed proteins, Panthenol, Allantoin, Seaweed & algae, Sodium PCA (sodium pyrrolidone carboxylic acid), Saccharide Isomerate, Sugar Alcohols (e.g. sorbitol),

[0103] 15

[0104] SUBSTITUTE SHEET (RULE 26) Hydroxy acids (e.g.. lactic acid and gluconolactone), Agave nectar, Betaine, Chitosan, Trehalose, Beta-glucan, Topical collagen, Galactoarabinan and propanediol

[0105]

[0075] Solvents used in the compositions of the present invention may include water, alcohols such as ethanol and isopropyl alcohol, alkanes such as C15-19 Alkane, silicone oils and mineral oils.

[0106]

[0076] Skin conditioning agents may be added to the compositions of the present invention, for example caprylic / capric triglyceride, alpha-glucan triglycerides, palmitoyl tripeptide-5, glycerine, diglucosyl gallic acid, panthenol, pantolactone, sodium stearoyl glutamate, lactic acid, hydrolysed hyaluronic acid, sodium hyaluronate and maltodextrin.

[0107]

[0077] Further natural extracts may be present in compositions of the present invention, for example Saccharomyces / Xylinum / Black Tea Ferment, Bellis Perennis (Daisy) Flower Extract, Thermus Thermophillus Ferment and Sphingomonas Ferment Extract.

[0108]

[0078] After formulation, the product is filled into an appropriate dispenser and shipped to the end user. Examples of final container may include a pump bottle, squeeze bottle, jar, tube or vial.

[0109]

[0079] The invention will now be illustrated by non-limiting examples of compositions according to the invention and by test results.

[0110] EXEMPLES

[0111] Example 1

[0112]

[0080] FIGS. 1A-1C show the results of studies conducted on cells utilizing

[0113] REGENIXIR® (SiLab) (https: / / www.silab.fr / en / products / skincare / 113 / regenixir) a yeast extract and assaying for SASP prevention efficacy by measuring the amounts of TNF-alpha; IL-6; and IL-8 produced by cells treated and untreated with REGENIXIR. As can be seen in FIGS. 1A-1C, cells treated with Reginixir exhibited a decreased level of TNF-alpha; IL-6; and IL-8 expression. Normal human fibroblasts were incubated with H2O2 for Ihour. Following H2O2 stress, media was removed and changed by culture medium containing the composition, cells were incubated at 37°C, 5% CO2 for 24hours. This stress was performed during seven days. Then the senescence-associated secretome (SASP) was quantified by using Elisa assay kits specific for IL6, IL8 and TNFa. Results were normalized with the total proteins content.

[0114]

[0081] FIG. 2 shows the results of study conducted on cells treated with REGENIXIR®

[0115] (SiLab) and assaying for SASP prevention efficacy by measuring the amount of MMP1 release by cells treated and untreated with REGENIXIR. As can be seen in FIG.2, MMP1 release

[0116] 16

[0117] SUBSTITUTE SHEET (RULE 26) increased with senescent cells compared to non-senescent cells. The treatment of senescent cells with REGENIXIR induced a significant decrease of MMP1. The senescence of normal human dermal fibroblasts was induced by replicative senescence according to the Hayflick model. Senescent cells were treated by the composition for 72 hours. Non treated senescent cells and non-treated non-senescent cells were cultured in the same conditions. MMP1 (matrix metalloproteinase- 1) release was assessed by using specific ELISA kit.

[0118]

[0082] FIG. 3 shows the results of study conducted on cells treated with REGENIXIR® (SiLab) and assaying for Senescence-Associated P-galactosidase activity (SA-P-gal) on cells treated and untreated with REGENIXIR. As can be seen in FIG.3, intracellular Senescence- Associated P-galactosidase activity was statistically reduced when cells were treated with the composition. Normal human dermal fibroblasts from aged donor were cultured and treated with the composition for 72 hours. Non-treated cells were cultured in the same conditions. Intracellular Senescence- Associated P-galactosidase activity (SA-P-gal) was then quantified using CellEvent Senescence Green Detection Kit.

[0119]

[0083] FIG. 4 shows the results of study conducted on cells treated with REGENIXIR® (SiLab) and assaying for SFRP4 (secreted frizzled-related protein 4) expression on cells treated and untreated with REGENIXIR. As can be seen in FIG.4, a clear decrease of SFRP4 expression was observed on cells treated with the composition. Normal human dermal fibroblasts from aged donor were cultured and treated with the composition for 72 hours. Nontreated cells were cultured in the same conditions. SFRP4 (secreted frizzled-related protein 4) were then quantified through immunostaining.

[0120]

[0084] The effect of REGENIXIR® on cellular senescence was studied on senescent normal human fibroblasts. The results show a significant reduction of intracellular SA-p-gal activity, and a decrease of SFRP4 (secreted frizzled-related protein 4) expression. The SASP profile was also modulated with significant decrease of interleukin-6 (IL-6), interleukin-8 (IL- 8), tumor necrosis factor-alpha (TNF-a), and matrix metalloproteinase- 1 (MMP-1) release. REGENIXIR® allows to treat and / or prevent cell senescence and modulate the SASP, limiting its adverse effects on neighboring non-senescent cells.

[0121] Example 2

[0122]

[0085] This study aimed to investigate a dual approach of an actives blend addressing cellular senescence via senostatic (also called senomorphic) and senolytic effects.

[0123] Method

[0124] 17

[0125] SUBSTITUTE SHEET (RULE 26)

[0086] A blend of biotechnological actives comprising adenosine, Schisandra sphenanthera and Saccharomyces cerevisiae extracts was tested for its senostatic and senolytic potential.

[0126]

[0087] To evaluate the dual approach, we used different technologies: i) For the senostatic approach, using fibroblasts artificially aged via the Hayflick method: SASP was assessed by measuring the release of cytokines and matrix metalloproteinases using enzyme-linked immunosorbent assay (ELISA) ii) For the senolytic approach, using aged fibroblasts of mature donor: SFRP4 was examined through immunostaining in Normal Human Fibroblasts from mature donor. Senescence-Associated P-galactosidase activity (SA-P-gal) was quantified using CellEvent Senescence Green Detection Kit.

[0127] Results

[0128]

[0088] Upon treatment, the in vitro results related to senostatic effect revealed a significant modulation of SASP profile, with decreased levels of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-a), and matrix metalloproteinase- 1 (MMP-1)

[0129]

[0089] Regarding senolytic action, experimentations resulted in a significant reduction of intracellular SA-P-gal activity. There was also a downregulation of SFRP4 (secreted frizzled-related protein 4).

[0130] Discussion and conclusions

[0131]

[0090] This study demonstrates the potential of a biotechnological actives blend made of Adenosine, Schisandra sphenanthera and Saccharomyces cerevisiae extracts in modulating cellular senescence by reducing senescent cells prevalence as demonstrated via beta galactosidase and SFRP4 down regulation, mitigating the SASP as shown in SASP assessment as revealed by SFRP4 downregulation in aged fibroblasts, thereby limiting its adverse effects on neighboring non-senescent fibroblasts.

[0132]

[0091] By minimizing cellular senescence, these actives can be beneficial for improving skin texture and decelerating the skin aging process.

[0133]

[0092] This anti senescence approach can be implemented in antiaging skincare strategies as a prerequisite allowing optimal efficacy of the active ingredients that help increase healthy cells, aged or not, in their metabolic functions and in particular in collagen synthesis.

[0134] Example 3

[0135] 18

[0136] SUBSTITUTE SHEET (RULE 26)

[0093] Cosmetic / dermatological composition

[0137]

[0094] A cosmetic / dermatological composition according to the present invention comprises the following ingredients:

[0138] Clauses

[0095] Clause 1 : Method of treating and / or preventing senescence comprising administering to a human or animal being a therapeutically effective amount of an extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-P- glucans with a molar mass of between 2 and 5 kDa

[0139]

[0096] Clause 2: Method of treating and / or preventing senescence comprising administering to a human or animal being a therapeutically effective amount of an extract of

[0140] Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-P- glucans with a molar mass of between 2 and 5 kDa, wherein senescence is replicative senescence, DNA-damage induced senescence or oncogene-induced senescence.

[0141]

[0097] Clause 3: Method of treating and / or preventing skin senescence comprising administering to a human or animal being a therapeutically effective amount of an extract of

[0142] Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-P- glucans with a molar mass of between 2 and 5 kDa.

[0143]

[0098] Clause 4: Method of treating and / or preventing the apparent signs of intrinsic skin ageing comprising administering to a human or animal being a therapeutically effective

[0144] 19

[0145] SUBSTITUTE SHEET (RULE 26) amount of an extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-P- glucans with a molar mass of between 2 and 5 kDa.

[0146]

[0099] Clause 5: Method of treating and / or preventing age-associated diseases in humans comprising administering to a human or animal being a therapeutically effective amount of an extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-P- glucans with a molar mass of between 2 and 5 kDa.

[0147]

[0100] Clause 6: The method of Clause 5, wherein the age-associated disease is cancer, heart disease or dementia.

[0148]

[0101] Clause 7: Method of treating and / or preventing a disease in humans according to any of Clauses 1-6, comprising administering a pharmaceutical composition comprising a pharmaceutically effective amount of an extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-P- glucans with a molar mass of between 2 and 5 kDa.

[0149]

[0102] Clause 8: Method according to Clause 7, wherein the composition is for enteral or parenteral administration, in particular intradermal or subcutaneous administration.

[0150]

[0103] It should be understood that although the present invention has been specifically disclosed by specific aspects and optional features, modification and variation of the concepts herein disclosed may be resorted to by those of ordinary skill in the art, and that such modifications and variations are considered to be within the scope of aspects of the present invention.

[0151] 20

[0152] SUBSTITUTE SHEET (RULE 26)

Claims

CLAIMSWhat is claimed is:

1. A cosmetic use of an active agent for treating and / or preventing skin senescence, wherein the agent is capable of inhibiting the senescence -associated secretory phenotype by i) mitigating release of IL-6, IL-8, TNF-oc and MMP1 (matrix metallopeptidase-1); ii) reducing activity of P-galactosidase; iii) reducing secreted frizzled-related protein 4 (SFRP 4) biosynthesis; and iv) reducing expression of p21 in fibroblasts.

2. The cosmetic use according to claim 1, wherein the active agent is an extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-P- glucans with a molar mass of between 2 and 5 kDa, and / or the fruit extract of Schisandra sphenanthera.

3. The cosmetic use according to claim 2, wherein skin senescence comprises the apparent signs of intrinsic skin ageing.

4. The cosmetic use according to claim 2, wherein the apparent signs of intrinsic skin ageing comprise hollowed cheeks and eye sockets; loss of skin firmness, sagging, thin and dry skin; fine wrinkles; decreased elasticity; aberrant pigmentation; and hair graying and loss.

5. The cosmetic use according to claim 4, wherein the extracts are present in a cosmetically useful amount.

6. The cosmetic use according to claim 5, wherein the active agent additionally comprises adenosine in a cosmetically useful amount.

7. Therapeutically effective amount of an active agent for use in treating and / or preventing skin senescence or age-associated diseases in humans, wherein the agent is capable of inhibiting the senescence -associated secretory phenotype by i) mitigating release of IL-6, IL-8, TNF-a and MMP1 (matrix metallopeptidase-1); ii) reducing activity of - galactosidase; iii) reducing secreted frizzled-related protein 4 (SFRP 4) biosynthesis; and iv) reducing expression of p21 in fibroblasts.21SUBSTITUTE SHEET (RULE 26)8. Therapeutically effective amount of an active agent for use according to claim 7, wherein the active agent is an extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-P- glucans with a molar mass of between 2 and 5 kDa, and / or the fruit extract of Schisandra sphenanthera.

9. Therapeutically effective amount of an active agent for use according to claim 8, wherein the active agent additionally comprises adenosine.

10. Therapeutically effective amount for use according to any of claims 7 to 9, wherein senescence is replicative senescence, DNA-damage induced senescence or oncogene- induced senescence.

11. Therapeutically effective amount for use according to any of claims 7 to 9, wherein the age-associated disease is cancer, heart disease or dementia.

12. Cosmetic or pharmaceutic composition comprising a cosmetically or pharmaceutically effective amount of an extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-P- glucans with a molar mass of between 2 and 5 kDa, and the fruit extract of Schisandra sphenanthera.

13. Cosmetic or pharmaceutic composition according to claim 12, further comprising adenosine.

14. Cosmetic or pharmaceutic composition according to any of claims 12 or 13, wherein the extract of Saccharomyces cerevisiae, said extract corresponding to the cytosolic fraction comprising oligo-P- glucans with a molar mass of between 2 and 5 kDa, is present in an amount of at least 0.00025% by weight, preferably between 0.001% and 2%, more preferably between 0.01% and 1%, even more preferably between 0.025% and 0.5%, even more preferably between 0.05% and 0.1%, most preferably 0.0625% by weight of the whole composition.

15. Cosmetic or pharmaceutic composition according to any of claims 12 to 14, wherein the composition is in the form of an oil-in-water emulsion, a water-in-oil emulsion, a multiple emulsion (Water / Oil / Water or Oil / Water / Oil), a microemulsion, a nanoemulsion, a solution, a suspension, a hydrodispersion, a gel, an ointment, a paste,22SUBSTITUTE SHEET (RULE 26)an aerosol foam, a spray, an aqueous gel, a powder, a foundation, a transdermal patch, a cream or a mask.

16. Cosmetic or pharmaceutic composition according to any of claims 12 to 15, wherein the composition is for enteral or parenteral administration, in particular intradermal or subcutaneous administration.

17. Cosmetic or pharmaceutic composition according to claim 13 comprising:SUBSTITUTE SHEET (RULE 26)

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