Nicotinamide adenine dinucleotide production activator, Sirt-1 activator, mitochondrial activator, GLS-1 activity inhibitor, pharmaceuticals, cosmetics, and food or beverages

Abstract

To provide a nicotinamide adenine dinucleotide production activator that can promote anti-aging. [Solution] The solution includes (i) or (ii) below. (i) Tamogitake mushroom or processed product thereof (ii) Nicotinamide mononucleotide and 5-deazaflavin

Description

Technical Field

[0001] The present invention relates to a nicotinamide adenine dinucleotide production activator, a Sirt-1 activator, a mitochondrial activator, a GLS-1 activity inhibitor pharmaceutical, a cosmetic, and a food or beverage.

Background Art

[0002] Nicotinamide adenine dinucleotide (hereinafter sometimes referred to as "NAD") is a coenzyme involved in redox reactions in major metabolic pathways in cells, such as glycolysis, the electron transport system, and the TCA cycle. NAD exists in cells as oxidized NAD + and reduced NADH, and it is important for cell function to maintain these amounts in an appropriate state. Also, the amount of NAD + has been pointed out to be related to aging and is also used as one of the indicators of aging-related diseases.

[0003] Nicotinamide mononucleotide (hereinafter sometimes referred to as "NMN") has attracted attention because it is converted into NAD in the body when administered orally (see, for example, Patent Document 1). According to Patent Document 1, it is described that adding cyclodextrin to NMN promotes the growth of health span compared to NMN alone.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] Therefore, there is a demand for substances that can increase the amount of NAD (especially the amount of NAD + amount) etc. other than NMN and achieve anti-aging. The object of the present invention is to provide a nicotinamide adenine dinucleotide production activator that can promote anti-aging.

[0006] Furthermore, in this invention, NAD in the body + We also investigated the point that when the amount increases, Sirt-1 is activated, and when Sirt-1 is activated, mitochondria are activated. Therefore, an objective of this invention is to provide a Sirt-1 activator and a mitochondrial activator that can promote anti-aging.

[0007] Furthermore, regarding anti-aging, it has been demonstrated that the accumulation of senescent cells in the body triggers the onset of so-called geriatric diseases, and it is believed that eliminating senescent cells can enable a full healthy lifespan. Among these, the induction of apoptosis in senescent cells dependent on glutamate metabolism is considered a promising approach, and GLS-1 inhibition is thought to lead to the elimination of senescent cells. Therefore, one of the objectives of this invention is to provide a GLS-1 activity inhibitor.

[0008] Furthermore, the present invention aims to provide pharmaceuticals, cosmetics, and foods or beverages containing the above-mentioned nicotinamide adenine dinucleotide production activator, Sirt-1 activator, mitochondrial activator, or GLS-1 activity inhibitor. [Means for solving the problem]

[0009] As a result of diligent research, the inventors of the present invention have found that the above problems can be solved by the following (1) to (4), and have completed the present invention. In other words, according to the present invention, (1) to (4) below (1) Nicotinamide adenine dinucleotide production activator containing (i) or (ii) below (i) Tamogitake mushroom or processed product thereof (ii) Nicotinamide mononucleotide and 5-deazaflavin (2) Sirt-1 activator comprising (i) or (ii) below (i) Tamogitake mushroom or processed product thereof (ii) Nicotinamide mononucleotide and 5-deazaflavin (3) Mitochondrial activators comprising at least one of the following (i), (iii), and (iv) (i) Tamogitake mushroom or processed product thereof (iii) Nicotinamide adenine dinucleotide and nicotinamide mononucleotide (iv) Nicotinamide adenine dinucleotide and 5-deazaflavin (4) GLS-1 activity inhibitors comprising (i) or (ii) below (i) Tamogitake mushrooms or processed products thereof (ii) Nicotinamide mononucleotide and 5-deazaflavin (5) A pharmaceutical product containing any of the following: (1) the nicotinamide adenine dinucleotide production activator, (2) the Sirt-1 activator, (3) the mitochondrial activator, or (4) the GLS-1 activity inhibitor. (6) Cosmetics containing any of the following: (1) the nicotinamide adenine dinucleotide production activator, (2) the Sirt-1 activator, (3) the mitochondrial activator, or (4) the GLS-1 activity inhibitor. (7) A food or beverage containing any of the following: (1) the nicotinamide adenine dinucleotide production activator, (2) the Sirt-1 activator, (3) the mitochondrial activator, or (4) the GLS-1 activity inhibitor. It will be provided. [Effects of the Invention]

[0010] The present invention provides a nicotinamide adenine dinucleotide production activator, a Sirt-1 activator, a mitochondrial activator, and a GLS-1 activity inhibitor that can promote anti-aging. Furthermore, the present invention provides pharmaceuticals, cosmetics, and foods or beverages containing a nicotinamide adenine dinucleotide production activator, a Sirt-1 activator, a mitochondrial activator, or a GLS-1 activity inhibitor.

Brief Description of the Drawings

[0011] [Figure 1] It is a diagram showing the results of examining the amount of NAD production in the examples. [Figure 2] It is a diagram showing the results of examining the Sirt-1 activity in the examples. [Figure 3] It is a diagram showing the results of examining the mitochondrial activity in the examples. [Figure 4] It is a diagram showing the results of examining the mitochondrial activity in the examples. [Figure 5] It is a diagram showing the results of examining the effect of removing senescent cells in the examples.

Modes for Carrying Out the Invention

[0012] (Nicotinamide adenine dinucleotide (NAD) production activator) The nicotinamide adenine dinucleotide production activator of the present invention contains the following (i) or (ii). (i) Ganoderma tsugae or a processed product thereof (ii) Nicotinamide mononucleotide (NMN) and 5-deazafavin

[0013] (Ganoderma tsugae or a processed product thereof) Ganoderma tsugae is an edible mushroom belonging to the genus Hirata of the family Hirataceae in the order Agaricales. In the present invention, Ganoderma tsugae or a processed product thereof is used as an active ingredient. Therefore, in the present invention, Ganoderma tsugae may be the whole or a part of the fruit body, and may be a wild one or an artificially cultivated one.

[0014] Methods for obtaining processed materials from Tamogitake mushrooms include extraction, heating, drying, crushing, pressing, and sterilization. These methods may be used individually or in combination of two or more. Furthermore, when obtaining processed materials from Tamogitake mushrooms, the entire mushroom may be used, or only parts such as the cap, stem, or volva may be used.

[0015] For example, the extraction process is not particularly limited, but solvent extraction, supercritical fluid extraction, etc., can be used. When performing solvent extraction, the extraction solvent used is not particularly limited, and water, organic solvents, and mixtures thereof can be used. Examples of organic solvents include alcohols such as methanol, ethanol, n-propanol, isopropanol, and n-butanol; glycols such as ethylene glycol and propylene glycol; ethyl acetate; acetone, etc. These organic solvents may be used individually or in combination of two or more. Alternatively, an aqueous solvent such as water may be mixed with an organic solvent.

[0016] Among these, water, ethanol, or an aqueous ethanol solution (a mixture of ethanol and water) is preferred. When using an aqueous ethanol solution, the concentration of ethanol is preferably 1-80 v / v% (EtOH), more preferably 5-50 v / v% (EtOH), and even more preferably 20-30 v / v% (EtOH).

[0017] Furthermore, when using water, tap water, purified water, or deionized water can be used, and the water temperature during extraction is preferably 60-100°C, more preferably 80-100°C, and even more preferably 90-100°C. Furthermore, when performing supercritical extraction, it is preferable to use carbon dioxide in a supercritical state.

[0018] Furthermore, when performing solvent extraction, extraction methods such as stirring extraction, immersion extraction, shaking extraction, reflux extraction, and ultrasonic extraction can be used. Among these, stirring extraction is particularly preferred.

[0019] Furthermore, the temperature during solvent extraction may be room temperature or under heated conditions. Also, the pressure during solvent extraction may be atmospheric pressure or under pressurized conditions. Furthermore, the extract obtained by solvent extraction may be subjected to filtration or other treatments as needed.

[0020] Alternatively, the extract obtained by solvent extraction may be dried and obtained as a powder. Known drying methods can be used, including spray drying, vacuum drying, and freeze-drying. These drying methods can also be used to obtain dried Tamogitake mushrooms.

[0021] The concentration of the active ingredient of Tamogitake mushroom or its processed product contained in the nicotinamide adenine dinucleotide (NAD) production activator of the present invention is preferably 0.01 μg / mL or higher, more preferably 0.1 μg / mL or higher, and preferably 100 μg / mL or lower.

[0022] (Nicotinamide mononucleotide (NMN) and 5-deazaflavin) Examples of NMN used in the present invention include α-NMN and β-NMN, but β-NMN is preferred. Derivatives of NMN or salts thereof may also be used.

[0023] NMN may be obtained by extraction and purification from animals, plants, microorganisms, etc., or it may be artificially synthesized and purified by methods such as chemical synthesis, enzymatic methods, or fermentation.

[0024] The concentration of NMN contained in the nicotinamide adenine dinucleotide (NAD) production activator of the present invention is preferably 0.01 μg / mL or higher, more preferably 0.1 μg / mL or higher, and preferably 100 μg / mL or lower.

[0025] The 5-deazaflavin used in this invention is obtained by replacing the nitrogen atom at the flavin 5 position of riboflavin (vitamin B2), a water-soluble vitamin, with a methylene group, and is represented by the following chemical formula (1).

[0026] [ka] (In formula (1), R1 and R2 represent a hydrogen atom or an alkyl group, respectively.)

[0027] The concentration of 5-deazaflavin contained in the nicotinamide adenine dinucleotide (NAD) production activator of the present invention is preferably 0.01 μg / mL or higher, more preferably 0.1 μg / mL or higher, and preferably 100 μg / mL or lower.

[0028] In the present invention, the mixing ratio of NMN and 5-deazaflavin is preferably 10:0.1 to 10:10 by mass ratio of NMN:5-deazaflavin, more preferably 10:0.5 to 10:7, and even more preferably 10:1 to 10:5.

[0029] The nicotinamide adenine dinucleotide (NAD) production activator of the present invention can increase the amount of NAD+ in cells, which is thought to lead to anti-aging effects.

[0030] (Sirt-1 activator) The Sirt-1 activator of the present invention comprises either (i) or (ii) below. (i) Tamogitake mushroom or processed product thereof (ii) Nicotinamide mononucleotide (NMN) and 5-deazaflavin

[0031] The following describes the ingredients of Tamogitake mushroom or its processed product, nicotinamide mononucleotide (NMN), and 5-deazaflavin. Furthermore, the mixing ratio of nicotinamide mononucleotide (NMN) and 5-deazaflavin can be the same as that of the nicotinamide adenine dinucleotide (NAD) production activator. The concentrations can also be the same. The Sirt-1 activator of the present invention is thought to be able to activate Sirt-1, which in turn is believed to lead to anti-aging effects.

[0032] (Mitochondrial activator) The mitochondrial activator of the present invention comprises at least one of the following (i), (iii), and (iv). (i) Tamogitake mushrooms or processed products thereof (iii) Nicotinamide adenine dinucleotide (NAD) and nicotinamide mononucleotide (NMN) (iV) Nicotinamide adenine dinucleotide (NAD) and 5-deazaflavin

[0033] The following applies to *Pleurotus ostreatus* or its processed products, nicotinamide mononucleotide (NMN), and 5-deazaflavin. The concentrations can also be the same.

[0034] Nicotinamide adenine dinucleotide (NAD), as described above, is a coenzyme involved in redox reactions in major intracellular metabolic pathways such as glycolysis, the electron transport chain, and the TCA cycle. The concentration of NAD contained in the mitochondrial activator of the present invention is preferably 0.01 μg / mL or higher, more preferably 0.1 μg / mL or higher, and preferably 100 μg / mL or lower.

[0035] The mixing ratio of nicotinamide adenine dinucleotide (NAD) to nicotinamide mononucleotide (NMN) is preferably 10:0.1 to 10:10 by mass ratio of nicotinamide adenine dinucleotide (NAD) to nicotinamide mononucleotide (NMN).

[0036] Furthermore, the mixing ratio of nicotinamide adenine dinucleotide (NAD) to 5-deazaflavin is preferably 10:0.1 to 10:10 in terms of the mass ratio of nicotinamide adenine dinucleotide (NAD) to 5-deazaflavin.

[0037] The mitochondrial activator of the present invention is thought to be able to activate mitochondria, which in turn can lead to anti-aging effects.

[0038] (GLS-1 activity inhibitors) The GLS-1 activity inhibitor of the present invention comprises either (i) or (ii) below. (i) Tamogitake mushroom or processed product thereof (ii) Nicotinamide mononucleotide (NMN) and 5-deazaflavin

[0039] The following describes the ingredients of Tamogitake mushroom or its processed product, nicotinamide mononucleotide (NMN), and 5-deazaflavin. Furthermore, the mixing ratio of nicotinamide mononucleotide (NMN) and 5-deazaflavin can be the same as that of the nicotinamide adenine dinucleotide (NAD) production activator. The concentrations can also be the same.

[0040] The GLS-1 activity inhibitor of the present invention is thought to eliminate senescent cells by inhibiting GLS-1 activity, thereby leading to anti-aging effects. Furthermore, since enhanced GLS-1 activity is observed in cancer cells, anti-cancer effects are also expected.

[0041] (Pharmaceuticals) Furthermore, the nicotinamide adenine dinucleotide (NAD) production activator, Sirt-1 activator, mitochondrial activator, and GLS-1 activity inhibitor of the present invention can also be incorporated into pharmaceuticals for these purposes. As pharmaceuticals, they can be used in both preventive and therapeutic drugs.

[0042] When incorporated into pharmaceuticals, the ingredient formulation may be used alone, or it may be mixed with generally pharmaceutically acceptable additives to form a pharmaceutical product. Regarding the form of administration, examples include oral formulations such as tablets, granules, capsules, pills, powders, liquids, suspensions, emulsions, syrups, elixirs, and extracts, or parenteral formulations such as injections, liquids, suppositories, ointments, patches, poultices, and lotions. There are no particular restrictions, and the appropriate form can be selected as appropriate depending on the purpose of treatment or prevention.

[0043] Furthermore, in the case of tablets, granules, pills, capsules, and powders, additives such as excipients, binders, disintegrants, and lubricants may be included. Examples of excipients include starch, carboxymethylcellulose, sucrose, dextrin, and corn starch.

[0044] Examples of binders include crystalline cellulose, crystalline cellulose-carmellose sodium, methylcellulose, hydroxypropylcellulose, low-substituted hydroxypropylcellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, carmellose sodium, ethylcellulose, carboxymethyl ethylcellulose, hydroxyethylcellulose, wheat starch, rice starch, corn starch, potato starch, dextrin, pregelatinized starch, partially pregelatinized starch, hydroxypropyl starch, pullulan, polyvinylpyrrolidone, aminoalkyl methacrylate copolymer E, aminoalkyl methacrylate copolymer RS, methacrylic acid copolymer L, methacrylic acid copolymer, polyvinyl acetal diethylaminoacetate, polyvinyl alcohol, gum arabic, gum arabic powder, agar, gelatin, white shellac, tragacanth, refined sucrose, and macrogol.

[0045] Examples of disintegrants include crystalline cellulose, methylcellulose, low-substituted hydroxypropylcellulose, carmellose, carmellose calcium, carmellose sodium, croscarmellose sodium, wheat starch, rice starch, corn starch, potato starch, partially pregelatinized starch, hydroxypropyl starch, carboxymethyl starch sodium, and tragacanth.

[0046] Examples of lubricants include wheat starch, rice starch, corn starch, stearic acid, calcium stearate, magnesium stearate, hydrated silicon dioxide, light anhydrous silicic acid, synthetic aluminum silicate, dried aluminum hydroxide gel, talc, magnesium aluminometasilicate, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, sucrose fatty acid esters, waxes, hydrogenated vegetable oils, and polyethylene glycol.

[0047] Furthermore, in the case of liquid preparations, syrups, suspensions, emulsions, and elixirs, in addition to commonly used inert diluents such as water and vegetable oil, colorants, flavoring agents, and fragrances may be included as additives.

[0048] Furthermore, in the case of injectable preparations, additives such as suspensions, emulsions, and solvents for use may be included. In the case of ointments and suppositories, additives such as fats, fatty oils, lanolin, petrolatum, paraffin, waxes, resins, plastics, bases, glycols, higher alcohols, water, emulsifiers, and suspending agents may be included. In the case of poultices, additives such as glycerin, water, water-soluble polymers, and superabsorbent polymers may be included. In the case of lotions, additives such as solvents, emulsifiers, and suspending agents may be included.

[0049] (cosmetics) Furthermore, the nicotinamide adenine dinucleotide (NAD) production activator, Sirt-1 activator, mitochondrial activator, and GLS-1 activity inhibitor of the present invention can also be incorporated into cosmetics. Examples of cosmetics include lotions, emulsions, facial washes, cleansers, serums, creams, foundations, eyebrow products, mascaras, eyeshadows, eyeliners, lipsticks, lip glosses, blushes, face powders, and nail polishes. Cosmetics can also be used in various forms, such as liquids, creams, solids, sticks, and powders.

[0050] (Food or beverage) Furthermore, the nicotinamide adenine dinucleotide (NAD) production activator, Sirt-1 activator, mitochondrial activator, and GLS-1 activity inhibitor of the present invention may be incorporated into foods and beverages. Examples of foods include bread, noodles, confectionery, processed meat products, processed seafood products, frozen foods, jellies, ice cream, dairy products, and various seasonings. In addition to general foods, they can also be incorporated into foods for specified health uses, quasi-drugs, health foods, and supplements. Examples of beverages include soft drinks, dairy beverages, alcoholic beverages, tea, black tea beverages, coffee, fruit juices, carbonated drinks, mineral water, and fruit and vegetable beverages.

[0051] Furthermore, foods and beverages containing the nicotinamide adenine dinucleotide (NAD) production activator, Sirt-1 activator, mitochondrial activator, and GLS-1 activity inhibitor of the present invention may be in the same form as oral formulations such as tablets, capsules, and syrups.

[0052] Furthermore, when manufacturing foods and beverages containing the nicotinamide adenine dinucleotide (NAD) production activator, Sirt-1 activator, mitochondrial activator, and GLS-1 activity inhibitor of the present invention, additives such as sweeteners, colorants, preservatives, thickeners, stabilizers, gelling agents, antioxidants, color fixatives, bleaching agents, emulsifiers, leavening agents, acidulants, glazing agents, and flavorings; solvents; and oils may be added as needed, to the extent that they do not interfere with the effects of the present invention. These additives may be used individually or in combination of two or more types.

[0053] The proportions of the nicotinamide adenine dinucleotide (NAD) production activator, Sirt-1 activator, mitochondrial activator, and GLS-1 activity inhibitor of the present invention incorporated into the above-mentioned foods and beverages can be appropriately adjusted according to the intended use, but the proportion of the ingredient formulation incorporated into the above-mentioned foods and beverages is preferably 0.01 to 20% by weight, more preferably 0.01 to 15% by weight, and even more preferably 0.1 to 10% by weight. [Examples]

[0054] The present invention will be described below with reference to examples, but the present invention is not limited thereto.

[0055] (Example 1: Investigation of NAD production levels) Samples 1-5 listed below were added to cultured skeletal muscle cells, and the cells were cultured at 37°C for 18 hours. After that, the cells were harvested, lysed, and the NAD levels in the cells were analyzed. + The quantity was measured. Quantitative analysis was performed using an NAD / NADH colorimetric kit. The results are shown in Figure 1.

[0056] Samples 1-5 are: Sample 1) NMN, Sample 2) NAD, Sample 3) 5-deazaflavin, Sample 4) Tamogitake mushroom (bio-got powder), and Sample 5) a mixture of NMN and 5-deazaflavin in a mass ratio of 10:3 (hereinafter referred to as "NMN + 5-deazaflavin"). The concentration of each sample was set to an upper limit of 60 μg / mL, and was added to cells by serial dilution 10 times to 6 μg / mL, 0.6 μg / mL, and 0.06 μg / mL. The same applies to Samples 1-5 in Examples 2-5 below.

[0057] As shown in Figure 1, among the four types of samples stimulated individually, the Tamogitake extract had the strongest NAD. + NAD, which shows production capacity + The production capacity was stronger than that of direct addition. Furthermore, an additive effect between NMN and 5-deazaflavin was observed.

[0058] (Example 2: Investigation of Sirt-1 activity) Samples 1-5 were added to cultured skeletal muscle cells, and the cells were cultured at 37°C for 18 hours. After that, the cells were harvested, lysed, and the level of Sirt-1-mRNA in the cells was measured quantitatively by RT-PCR. The results are shown in Figure 2.

[0059] As shown in Figure 2, Sirt-1 levels showed the highest increase with NMN stimulation, but the *Pleurotus ostreatus* also showed stable Sirt-1 levels regardless of concentration. Although an additive effect between NMN and 5-deazaflavin could not be confirmed, the concentrations in c and d for each sample could be considered non-physiologically high, so feedback may have occurred.

[0060] (Example 3: Examination of mitochondrial activity - Part 1) Cultured skeletal muscle cells were pre-treated by adding a fluorescent probe (MitoBright LT Green) to activate mitochondria, which increased the fluorescence intensity. The test sample was then added, and the cells were cultured at 37°C for 18 hours. The fluorescence within the cells was then observed using a fluorescence microscope. Since it was not possible to quantify the total fluorescence amount, all cells were harvested, lysed, and the fluorescence amount within the cells was measured. The results are shown in Figure 3.

[0061] As shown in Figure 3, the fluorescence levels of the samples were measured at each concentration, but a clear difference was observed only in the 6 μg / mL stimulation group. A clear increase in fluorescence levels, i.e., mitochondrial activation, was observed in NAD and Pleurotus ostreatus. No additive effect between NMN and 5-deazaflavin was observed.

[0062] (Example 4: Examination of mitochondrial activity - Part 2) Adipocytes were pre-treated by adding a fluorescent probe (MitoBright LT Green) to activate mitochondria, which increased the fluorescence intensity. The test sample was then added, and the cells were incubated at 37°C for 18 hours. The fluorescence intensity was then measured by observing the fluorescence within the cells using a fluorescence microscope. The results are shown in Figure 4.

[0063] As shown in Figure 4, NAD and Pleurotus erythrosora showed high levels. At 60 μg / mL, the concentration dependence was slightly disrupted, and a tendency toward suppression was observed, which may be due to cytotoxicity.

[0064] Previous studies on energy metabolism have provided evidence supporting the commonly reported phenomena of increased NAD levels and elevated Sirt-1 gene levels. However, mitochondrial activation was only observed when NAD was directly added or when complex components such as Pleurotus ostreatus were used. While it was confirmed that NMN and 5-deazaflavin do not contribute to activation on their own, and do not inhibit the action of NAD in the presence of NAD, no synergistic effects were observed. Furthermore, no difference in the characteristics of NMN and 5-deazaflavin in mitochondrial activation could be found.

[0065] (Example 5: Investigation of senescent cell removal effect) Cancer cells were treated with the following samples 1-5 and cultured at 37°C for 18 hours. The cells were then harvested, lysed, and the intracellular GLS-1 levels were measured quantitatively by RT-PCR. The results are shown in Figure 5(a). Similar studies were also performed on normal cells. The results are shown in Figure 5(b).

[0066] As shown in Figure 5, cancer cells enhance glutamine metabolism to prevent cell death, and therefore GLS-1 is already in an activated state. However, NMN, Tamogitake mushroom extract, and NMN+5-deazaflavin formulations were found to have an inhibitory effect on this activation. In normal cells, some inhibition was observed at high concentrations of NMN and NMN+5-deazaflavin formulations, but no particularly strong inhibitory effect was observed at physiological concentrations.

Claims

1. A nicotinamide adenine dinucleotide production activator comprising (i) or (ii) below. (i) Tamogitake mushroom or processed product thereof (ii) Nicotinamide mononucleotide and 5-deazaflavin

2. A Silt-1 activator comprising (i) or (ii) below. (i) Tamogitake mushroom or processed product thereof (ii) Nicotinamide mononucleotide and 5-deazaflavin

3. A mitochondrial activator comprising at least one of the following (i), (iii), and (iv). (i) Tamogitake mushroom or processed product thereof (iii) Nicotinamide adenine dinucleotide and nicotinamide mononucleotide (iv) Nicotinamide adenine dinucleotide and 5-deazaflavin

4. A GLS-1 activity inhibitor comprising (i) or (ii) below. (i) Tamogitake mushroom or processed product thereof (ii) Nicotinamide mononucleotide and 5-deazaflavin

5. A pharmaceutical product comprising any one of the nicotinamide adenine dinucleotide production activator described in claim 1, the Sirt-1 activator described in claim 2, the mitochondrial activator described in claim 3, and the GLS-1 activity inhibitor described in claim 4.

6. A cosmetic product containing any of the nicotinamide adenine dinucleotide production activator described in claim 1, the Sirt-1 activator described in claim 2, the mitochondrial activator described in claim 3, and the GLS-1 activity inhibitor described in claim 4.

7. A food or beverage containing any of the nicotinamide adenine dinucleotide production activator described in claim 1, the Sirt-1 activator described in claim 2, the mitochondrial activator described in claim 3, and the GLS-1 activity inhibitor described in claim 4.

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