Anti-aging agent, oral composition for Anti-aging, and use of compound

Abstract

This anti-aging agent contains, as an active ingredient, a compound represented by formula (I), a racemate thereof, or a salt thereof. (In formula (I), a carbon atom in a glycerol skeleton may have a substituent, an oxygen atom bound to R1 is represented by *, and R1 is a compound that may have a substituent.)

Description

Use of anti-aging agents, oral anti-aging compositions and compounds

[0001] The present invention relates to anti-aging agents, oral compositions and compounds for use in anti-aging.

[0002] Nicotinamide adenine dinucleotide (NAD ＋ ) is a universal and essential coenzyme involved in cellular redox reactions. ＋ The main biosynthetic pathway of nicotinamide is the salvage pathway, which is controlled by the rate-limiting enzyme nicotinamide phosphoribosyltransferase (NAMPT). In this biosynthetic pathway, NAMPT converts nicotinamide to nicotinamide mononucleotide (NMN). The generated NMN is converted to NAD by nicotinamide mononucleotide adenylyltransferase (NMNAT1). ＋ is converted to

[0003] NAD ＋ functions as a coenzyme for a group of enzymes called sirtuins. Sirtuins are proteins believed to have the function of suppressing aging, and seven types of sirtuins (SIRT1 to SIRT7) are known in humans. In particular, activation of SIRT1 has a variety of anti-aging effects, such as cellular rejuvenation and increased metabolism.

[0004] Non-Patent Document 1 shows that calorie intake restriction in monkeys exhibits anti-aging effects. Non-Patent Document 2 shows that the anti-aging effects of calorie intake restriction in mice are SIRT1 dependent. Furthermore, Non-Patent Document 3 shows that 25% calorie restriction for 6 months induces SIRT1 expression in humans. Based on the above findings, it is expected that activation of NAMPT and SIRT1 will have anti-aging effects in humans.

[0005] It is known that the expression of NAMPT and SIRT1 decreases with age (Non-Patent Documents 4 and 5). Patent Document 1 discloses 2-palmitoylmonoglycerol as a substance that increases the expression of NAMPT and SIRT1.

[0006] Japanese Patent Application Laid-Open No. 2022-159178

[0007] Ricki J. Colman, 10 others, “Caloric restriction delays disease onset and mortality in rhesus” monkeys”, Science, 2009, 325 (5937), 201-204 Danica Chen, and 3 others, “Increase in Activity During Calorie Restriction Requires Sirt1”, Science, 2005, 310 (5754), 1641 Anthony E. Civitarese, 7 others, “Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans”, PLoS Medicine, 2007, 4(3), e76Jun Yoshino, 3 others, “Nicotinamide Mononucleotide, a Key NAD+ Intermediate, Treats the Pathophysiology of Diet-and Age-Induced Diabetes in Mice", Cell Metabolism, 2011, 14, 528-536 Cui Chen, 3 others, “SIRT1 and aging related signaling pathways”, Mech Aging Dev, 2020, 187, 111215

[0008] Restricting calorie intake may be a burden to the practitioner because it takes a long time for the effects to be seen. In order to suppress various physiological declines associated with aging, it is desired to increase the expression of NAMPT and SIRT1 safely and easily even in elderly people.

[0009] The present invention has been made in view of the above circumstances, and aims to provide an anti-aging agent, an oral composition for anti-aging, and use of a compound that can increase the expression of NAMPT and SIRT1.

[0010] The anti-aging agent according to the first aspect of the present invention comprises a compound represented by formula (I), its racemate or a salt thereof as an active ingredient. (In formula (I), the carbon atoms of the glycerol skeleton may have a substituent, and R １ The oxygen atom bonded to is *, and R １ may have a substituent It is.)

[0011] The anti-aging oral composition according to the second aspect of the present invention comprises a compound represented by formula (I), its racemate or a salt thereof as an active ingredient. (In formula (I), the carbon atoms of the glycerol skeleton may have a substituent, and R １ The oxygen atom bonded to is *, and R １ may have a substituent It is.)

[0012] A use according to a third aspect of the present invention is use of a compound represented by formula (I), its racemate or a salt thereof for the manufacture of an anti-aging agent or an oral composition for anti-aging. (In formula (I), the carbon atoms of the glycerol skeleton may have a substituent, and R １ The oxygen atom bonded to is *, and R １ may have a substituent It is.)

[0013] According to the present invention, the expression of NAMPT and SIRT1 can be increased.

[0014] FIG. 1 is a diagram showing the relative expression level of NAMPT according to Test Example 1. FIG. 2 is a diagram showing the relative expression level of SIRT1 according to Test Example 1. FIG. 3 is a diagram showing the relative expression level of NRF1 according to Test Example 1. FIG. 4 is a diagram showing the relative expression level of UQCRC1 according to Test Example 1. FIG. 5 is a diagram showing the relative expression level of ATP5A1 according to Test Example 1. FIG. 6 is a diagram showing the relative expression level of NAMPT according to Test Example 2. FIG. 7 is a diagram showing the relative expression level of SIRT1 according to Test Example 2.

[0015] Embodiments of the present invention will be described with reference to the drawings. Note that the present invention is not limited to the following embodiments and drawings. Note that in the following embodiments, the expressions "have," "include," or "contain" also include the meaning of "consisting of" or "consisting of."

[0016] The anti-aging agent according to the present embodiment contains, as an active ingredient, a compound represented by formula (I), its racemate, or a salt thereof (hereinafter also referred to as "compound, etc."). The carbon atoms of the glycerol skeleton in formula (I) may have a substituent. Examples of the substituent that the carbon atoms of the glycerol skeleton may have include a hydroxy group, a halogen, an aryl group, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms.

[0017]

[0018] In formula (I), R １ The oxygen atom bonded to is *, and R １ may have a substituent It is. １ Examples of the substituent that may be contained in the alkyl group include a hydroxy group, a halogen atom, an aryl group, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms.

[0019] Preferably, the compound according to this embodiment is represented by the following formula (II):

[0020]

[0021] The salt of the above compound is not particularly limited, but is preferably a pharmacologically acceptable salt. The salt of the above compound may be either an acid salt or a basic salt. Examples of the salt include alkali metal salts such as lithium salt, sodium salt, and potassium salt; alkaline earth metal salts such as magnesium salt and calcium salt; inorganic acid salts such as hydrochloride, hydrobromide, sulfate, nitrate, oxalate, and phosphate; acetate, propionate, hexanoate, cyclopentanepropionate, glycolate, pyruvate, lactate, malonate, succinate, malate, fumarate, tartrate, citrate, benzoate, o-(4-hydroxybenzoyl)benzoate, cinnamate, mandelate, methanesulfonate, ethoxylated ... and organic acid salts such as benzenesulfonate, 1,2-ethanedisulfonate, 2-hydroxyethanesulfonate, benzenesulfonate, p-chlorobenzenesulfonate, 2-naphthalenesulfonate, p-toluenesulfonate, camphorsulfonate, glucoheptanoate, 3-phenylpropionate, trimethyl acetate, tert-butyl acetate, lauryl sulfate, gluconate, glutamate, hydroxynaphthoate, salicylate, stearate, trifluoroacetate (TFA) salt, maleate, and muconate.

[0022] The compounds according to the present embodiment can be synthesized by known methods. １ When synthesizing a compound in which R is ethanolamine, first, arachidonic acid is reacted with tert-butyl(2-((tert-butoxy((R)-2-hydroxy-3-(octadecyloxy)propoxy)phosphoryl)oxy)ethyl)carbamate using a condensing agent. The resulting product is deprotected by the action of a strong acid such as trifluoroacetic acid, thereby obtaining the compound according to this embodiment. The condensing agent is not particularly limited, and examples that can be used include 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) hydrochloride, dicyclohexylcarbodiimide (DCC), HATU, HBTU, TATU, TBTU, and diphenylphosphoryl azide (DPPA). A nucleophile such as dimethylaminopyridine (DMAP) may be used to promote the dehydration condensation reaction by the condensing agent.

[0023] The plasmalogen content in the anti-aging agent according to the present embodiment is adjusted as appropriate. For example, the anti-aging agent may contain, as an active ingredient, 0.000001 to 99.9 mass%, 0.00001 to 99.8 mass%, 0.0001 to 99.7 mass%, 0.001 to 99.6 mass%, 0.01 to 99.5 mass%, 0.1 to 99 mass%, 0.5 to 60 mass%, 1 to 50 mass%, or 1 to 2 mass% of a compound or the like.

[0024] The anti-aging agent according to this embodiment is administered to cells, living tissues, organisms, animals, etc. The anti-aging agent as a pharmaceutical is administered to humans and animals. The animals are preferably mammals, and more specifically, include dogs, cats, cows, pigs, horses, sheep, deer, etc.

[0025] The route of administration of the anti-aging agent according to this embodiment to humans is not particularly limited. The anti-aging agent is preferably used as an external preparation, an injection, or an oral preparation. The anti-aging agent may include, for example, a compound and a pharmacologically acceptable carrier. The pharmacologically acceptable carrier is any of various organic or inorganic carrier substances used as formulation ingredients. Examples of pharmacologically acceptable carriers include excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, etc. in solid preparations, and solvents, solubilizers, suspending agents, isotonicity agents, buffers, flavoring agents, etc. in liquid preparations. Furthermore, additives such as preservatives, antioxidants, colorants, and sweeteners may be added as needed.

[0026] Examples of excipients include lactose, sucrose, D-mannitol, D-sorbitol, starch, pregelatinized starch, dextrin, crystalline cellulose, low-substituted hydroxypropyl cellulose, sodium carboxymethylcellulose, gum arabic, pullulan, soft anhydrous silicic acid, synthetic aluminum silicate, magnesium aluminometasilicate, xylitol, sorbitol, and erythritol.

[0027] Examples of binders include, in addition to the above-mentioned excipients, pregelatinized starch, sucrose, gelatin, gum arabic, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, crystalline cellulose, sucrose, D-mannitol, trehalose, dextrin, pullulan, hydroxypropyl cellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, and the like.

[0028] Examples of disintegrants include, in addition to the above-mentioned excipients, lactose, sucrose, starch, carboxymethylcellulose, carboxymethylcellulose calcium, croscarmellose sodium, carboxymethylstarch sodium, low-substituted hydroxypropylcellulose, soft anhydrous silicic acid, calcium carbonate, etc.

[0029] Examples of lubricants include magnesium stearate, calcium stearate, talc, colloidal silica, and polyethylene glycol.

[0030] Examples of stabilizers include parahydroxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride, acetic anhydride, sorbic acid, etc. Examples of flavoring agents include sweeteners, acidulants, fragrances, etc.

[0031] Examples of solvents include water for injection, physiological saline, Ringer's solution, alcohol, propylene glycol, polyethylene glycol, sesame oil, corn oil, olive oil, cottonseed oil, etc. Examples of solubilizers include polyethylene glycol, propylene glycol, D-mannitol, trehalose, benzyl benzoate, ethanol, tris(hydroxymethyl)aminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate, sodium salicylate, sodium acetate, etc.

[0032] Examples of suspending agents include surfactants such as stearyl triethanolamine, sodium lauryl sulfate, lauryl aminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, and glycerin monostearate; hydrophilic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, and hydroxypropylcellulose; polysorbates, and polyoxyethylene hydrogenated castor oil.

[0033] Examples of isotonic agents include sodium chloride, glycerin, D-mannitol, D-sorbitol, glucose, xylitol, fructose, etc. Examples of buffering agents include buffer solutions such as phosphates, acetates, carbonates, and citrates.

[0034] Examples of preservatives include parahydroxybenzoates, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, sorbic acid, etc. Examples of antioxidants include sulfites, ascorbic acid, etc. Examples of coloring agents include water-soluble colored tar dyes, lake dyes, natural dyes, etc. Examples of sweeteners include saccharin sodium, dipotassium glycyrrhizinate, aspartame, stevia, etc.

[0035] The anti-aging agent according to this embodiment is produced by a known method and is provided in the form of, for example, a liquid, cream, ointment, tablet, granule, fine granule, powder, tablet, capsule, or the like.

[0036] The dosage of the anti-aging agent according to this embodiment is determined as appropriate depending on the age, weight, symptoms, etc., of the human or animal to which it is administered. The anti-aging agent is administered so that the compound or the like is in an effective amount. An effective amount is the amount of the compound or the like necessary to achieve the desired result, i.e., the amount necessary to delay, inhibit, prevent, reverse, or cure the progression of the condition being treated or treated.

[0037] The dosage of the anti-aging agent according to this embodiment is, for example, 0.000001 μg or more, preferably 1 μg or more or 500 μg or more, and more preferably 1000 μg or more per day for an adult. The upper limit is, for example, 20,000 μg per day, preferably 10,000 μg. The anti-aging agent can be administered once or multiple times per day. The anti-aging agent may also be administered at various administration frequencies, such as every other day, once a week, every other week, or once a month. However, amounts outside the above ranges can also be used as needed.

[0038] As shown in the examples below, the compounds serving as active ingredients in the anti-aging agent according to this embodiment increase the expression levels of NAMPT and SIRT1, thereby achieving an anti-aging effect.

[0039] The compounds according to this embodiment may be used as reagents for enhancing the expression of NAMPT, SIRT1, NRF1, UQCRC1 and ATP5A1 in in vitro and in vivo experiments.

[0040] In another aspect of the present embodiment, there is provided an anti-aging oral composition. Specific examples of the oral composition include supplements, food and drink compositions, functional foods, and food additives.

[0041] The form of the supplement is not particularly limited and may be any form such as tablets, powders, granules, capsules, sugar-coated tablets, films, lozenges, chewable tablets, solutions, emulsions, suspensions, etc. The supplement may contain any ingredient typically used as a supplement.

[0042] The term "functional food" refers to food or beverages taken for the purpose of maintaining health, and includes foods with health claims, foods with functional health uses, foods with functional claims, foods with nutrient functions, health foods, and nutritional supplements. Functional foods are preferably foods with health claims or foods with nutrient functions. When commercializing the anti-aging oral composition as a functional food, various additives used in foods, specifically colorants, preservatives, thickening stabilizers, antioxidants, bleaching agents, antibacterial and antifungal agents, acidulants, sweeteners, seasonings, emulsifiers, strengthening agents, manufacturing agents, flavorings, etc., may be added to the anti-aging oral composition.

[0043] Functional foods may be either foods or beverages, and are not particularly limited as long as they can be taken orally. Examples of functional foods include beverages, confectioneries, processed grain products, paste products, dairy products, seasonings, etc. Examples of beverages include nutritional drinks, soft drinks, black tea, green tea, etc. Examples of confectioneries include candy, cookies, tablet candy, chewing gum, jelly, etc. Examples of processed grain products include noodles, bread, cooked rice, biscuits, etc. Examples of paste products include sausages, ham, kamaboko, etc. Examples of dairy products include butter, yogurt, etc.

[0044] The anti-aging oral composition may be added to food as a food additive, which may be in the form of a paste, gel, powder, liquid, suspension, emulsion, granules, or the like, to facilitate its addition to food.

[0045] The anti-aging oral composition according to this embodiment may contain water, vitamins, minerals, organic acids, organic bases, fruit juice, flavors, functional ingredients, food additives, etc., within the range in which the anti-aging effect is maintained. The anti-aging oral composition can be produced by a known method, adding ingredients other than the above-mentioned compound as the active ingredient, as needed.

[0046] The anti-aging oral composition may be divided and stored in one or more containers so that the daily intake amount is the above-mentioned intake amount. In this case, it is preferable that one container stores one day's worth of the anti-aging oral composition.

[0047] The anti-aging oral composition is provided in a form that can be distinguished from other products in that it contains the above-mentioned compound, etc. and is used for anti-aging. For example, at least one of the packaging, instructions, and promotional materials for the product relating to the anti-aging oral composition indicates that it has an anti-aging effect.

[0048] When the anti-aging oral composition according to this embodiment is provided as a food or beverage composition, it may be provided or sold as a food or beverage labeled with uses (including health uses) such as anti-aging effects, anti-aging, and reduction of aging risks. The act of "labeling" includes all acts for informing consumers of the above uses. Any expression that can recall or infer the above uses is considered an act of "labeling," regardless of the purpose of the labeling, the content of the labeling, the object or medium used for labeling, etc.

[0049] It is preferable that the "labeling" be done in an expression that allows consumers to directly recognize the intended use. Specifically, this includes acts of transferring, delivering, displaying for the purpose of transferring or delivering, or importing food and beverage products or product packaging that lists the intended use, displaying or distributing advertisements, price lists, or transaction documents that list the intended use, or providing information containing the above-mentioned uses by electromagnetic means (such as the Internet).

[0050] "Labeling" includes labeling as health food, functional food, enteral nutritional food, special dietary food, health functional food, food for specified health uses, food with nutrient functions, food with functional claims, quasi-drugs, etc. Among these, labeling approved under systems related to foods for specified health uses, foods with nutrient functions, or foods with functional claims, or similar systems, is particularly included. Specific examples include labeling as a food for specified health uses, labeling as a conditional food for specified health uses, labeling that indicates an effect on the structure or function of the body, labeling that reduces disease risk, and labeling of functionality based on scientific evidence. More specifically, labeling as a food for specified health uses (especially labeling of health uses) and similar labeling are typical examples.

[0051] In another aspect of the present embodiment, there is provided use of the compound, etc. for the manufacture of an anti-aging agent or an oral composition for anti-aging. In another aspect of the present embodiment, there is provided an anti-aging method comprising the step of administering the compound, etc. to a subject. In another aspect of the present embodiment, there is provided the compound, etc. for use in anti-aging.

[0052] The present invention will be explained in more detail with reference to the following examples, but the present invention is not limited to these examples.

[0053] Example 1 Synthesis of Compound KIT13 KIT13 was synthesized as a compound according to formula (I) as follows.

[0054]

[0055] To a dichloromethane solution (3 mL) of tert-butyl (2-((tert-butoxy((R)-2-hydroxy-3-(octadecyloxy)propoxy)phosphoryl)oxy)ethyl)carbamate (187 mg, 0.30 mmol), EDC hydrochloride (115 mg, 0.60 mmol), DMAP (37 mg, 0.30 mmol), and arachidonic acid (100 mg, 0.33 mmol) were added at room temperature, and the mixture was stirred for 20 hours. The reaction solution was diluted with ethyl acetate and then washed with water. The ethyl acetate layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by column chromatography to give the desired (2R)-1-((tert-butoxy(2-((tert-butoxycarbonyl)amino)ethoxy)phosphoryl)oxy)-3-(octadecyloxy)propan-2-yl(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate as a colorless liquid (260 mg, 95%).

[0056] 1 ​H NMR (500 MHz, CDCl3) δ 5.43-5.31 (m, 8H), 5.16 (quin, J = 4.9 Hz, 1H), 5.16 (br, 1H), 4.21 (m, 1H), 4.14-4.09 (m, 1H), 4.07-4.02 (m, 2H), 3.55 (d, J = 5.3 Hz, 2H), 3.47-3.38 (m, 5.3 Hz), 2.85-2.79 (m, 6H), 2.35 (t, J = 7.6 Hz), 2.12 (q, J = 7.0 Hz, 2H), 2.06 (q, J = 7.1 Hz, 2H), 1.74-1.67 (m, 2H), 1.56-1.54 (m, 2H), 1.502 (s, 9H, one diastereomer), 1.496 (s, 9H, the other diastereomer), 1.39-1.25 (m, 38H), 0.90-0.87 (m, 6H).

[0057]

[0058] To a dichloromethane solution (2 mL) of (2R)-1-((tert-butoxy(2-((tert-butoxycarbonyl)amino)ethoxy)phosphoryl)oxy)-3-(octadecyloxy)propan-2-yl(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate (260 mg, 0.29 mmol), 2 mL of trifluoroacetic acid was added at room temperature, and the mixture was stirred for 3 hours. The reaction mixture was concentrated under reduced pressure to give the desired 2-(hydroxy((R)-2-(((5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoyl)oxy)-3-(octadedecyloxy)propoxy)phosphoryl)oxy)ethane-1-ammonium 2,2,2-trifluoroacetate (KIT13) as a colorless liquid (249 mg, quant.).

[0059] 1 ​H NMR (500 MHz, CDCl3) δ 11.31 (br, 1H), 5.41-5.31 (m, 8H), 5.16-5.15 (m, 1H), 4.17 (br, 2H), 4.07-4.00 (m, 2H), 3.54 (d, J = 4.9 Hz, 2H), 3.45-3.39 (m, 2H), 3.27 (br), 2.84-2.78 (m, 6H), 2.35 (t, J = 7.4 Hz, 2H), 2.10 (q. J = 7.1 Hz, 2H), 2.05 (q. J = 7.2 Hz, 2H), 1.69-1.66 (m, 2H), 1.54-1.51 (m, 2H), 1.39-1.25 (m, 38H), 0.90-0.86 (m, 6H).

[0060] Test Example 1: Examination of the effect of compound KIT13 on the expression levels of NAMPT and SIRT1 Human hair outer root sheath cells (HHORSC, ScienCell Research Laboratories, #2420) were cultured for 7 hours in a culture medium containing 5 μg / ml of KIT13. Note that Mesenchymal Stem Cell Medium (ScienCell Research Laboratories, #7501) was used as the culture medium for HHORSC. As a control (-), HHORSC were cultured in a culture medium not containing KIT13.

[0061] RNA was extracted from the cells using TRIzol (Thermo Fisher Scientific). Next, first-strand cDNA was prepared using PrimeScript RT Master Mix (Takara). mRNA expression of the target gene and endogenous control gene was detected by real-time PCR using TB Green Premix Ex Taq II (Takara) on a T100™ Thermal Cycler (BIO-RAD). The target genes were NAMPT, SIRT1, and NRF1, UQCRC1, and ATP5A1, whose expression is induced by SIRT1 activation (Yuanyuan Huang et al., "Resveratrol-induced Sirt1 phosphorylation by LKB1 mediates mitochondrial metabolism," J. Biol. Chem., 2021, 297(2), 100929). 18S ribosomal RNA (18S rRNA) was used as an endogenous control gene, and the measured values ​​of each gene were normalized to the measured values ​​of 18S rRNA. The base sequences of the primers used in real-time PCR are shown in Table 1.

[0062]

[0063] (Results) As shown in Figures 1 and 2, KIT13 significantly increased the expression levels of NAMPT and SIRT1. Furthermore, as shown in Figures 3, 4, and 5, the expression levels of NRF1, UQCRC1, and ATP5A1 also increased. The increase in the expression levels of NRF1, UQCRC1, and ATP5A1 is dependent on SIRT1 activation.

[0064] Test Example 2: Study of the effect of compound KIT13 on the expression levels of NAMPT and SIRT1 in vivo in mice. KIT13 was administered in drinking water at a dose of 20 μg / kg to 4-week-old male c57BL6J mice (5 mice per group, n=5) for 4 weeks. Thigh muscles were collected from each mouse and analyzed as follows.

[0065] The thigh muscles were homogenized with Buffer A (0.25 M sucrose, 10 mM Hepes-KOH (pH 7.5), 1 mM EDTA, protease inhibitor cocktail) using an 18G to 25G needle and disrupted. RNA was extracted from the cells using the same protein amount using TRIzol (Thermo Fisher Scientific). Next, first-strand cDNA was prepared using PrimeScript RT Master Mix (Takara). The mRNA expression of the target gene and endogenous control gene was detected by real-time PCR using TB Green Premix Ex Taq II (Takara) in a T100™ Thermal Cycler (BIO-RAD). The target genes were NAMPT and SIRT1, and the endogenous control gene was β-actin. The measured values ​​of each gene were normalized to the measured value of β-actin. The base sequences of the primers used in real-time PCR are shown below.

[0066]

[0067] (Results) As shown in Figures 6 and 7, KIT13 significantly increased the expression levels of NAMPT and SIRT1 in muscle.

[0068] The present invention allows various embodiments and modifications without departing from the broad spirit and scope of the present invention. Furthermore, the above-described embodiments are intended to illustrate the present invention and do not limit the scope of the present invention. That is, the scope of the present invention is defined by the claims, not the embodiments. Various modifications made within the scope of the claims and the meaning of the invention equivalent thereto are considered to be within the scope of the present invention.

[0069] This application is based on Japanese Patent Application No. 2023-146775, filed on September 11, 2023. The entire specification, claims, and drawings of Japanese Patent Application No. 2023-146775 are incorporated herein by reference.

[0070] The present invention is useful as an anti-aging agent.

Claims

1. An anti-aging agent comprising a compound represented by formula (I), its racemate or a salt thereof as an active ingredient. (In formula (I), the carbon atom of the glycerol skeleton may have a substituent, and R １ The oxygen atom bonded to is *, and R １ may have a substituent It is.) 2. An anti-aging oral composition comprising a compound represented by formula (I), its racemate or a salt thereof as an active ingredient. (In formula (I), the carbon atom of the glycerol skeleton may have a substituent, and R １ The oxygen atom bonded to is *, and R １ may have a substituent It is.) 3. Use of a compound represented by formula (I), its racemate or a salt thereof for the manufacture of an anti-aging agent or an oral composition for anti-aging. In formula (I), the carbon atom of the glycerol skeleton may have a substituent, and R １ The oxygen atom bonded to is *, and R １ may have a substituent It is.)

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