Anti-aging agent and anti-aging method

Abstract

To provide an anti-aging agent, etc., that is safe to ingest over a long period of time and can effectively prevent the progression of aging. [Solution] Nicotinamide mononucleotide is used as the active ingredient.

Description

[Technical Field]

[0001] The present invention relates to an anti-aging agent and an anti-aging method. [Background technology]

[0002] Thanks to advances in medicine and improvements in public health, human life expectancy is steadily increasing. Recent reports indicate that in Japan, by 2060, the average life expectancy for men is projected to reach 84.19 years and for women 90.93 years, with women's average life expectancy exceeding 90 years. Furthermore, the proportion of the population aged 65 and over (the aging rate) in Japan's total population is approximately 25%, indicating a rapidly aging society. It is predicted that the aging rate will continue to rise along with the increase in average life expectancy, and the aging society will persist.

[0003] Incidentally, one of the problems facing Japan's aging society is that the increase in healthy life expectancy—the period during which daily life is not restricted—is smaller than the increase in average life expectancy, and the gap between average life expectancy and healthy life expectancy is widening. Even though aging is an unavoidable phenomenon for all living things, everyone desires to slow down aging as much as possible, extend healthy life expectancy, and live a long life in good health.

[0004] In order to address the problems of an aging society, research in the field of anti-aging medicine has become increasingly active in recent years. This field views aging as a disease and aims to delay the onset of aging itself through treatment. Anti-aging medicine covers a wide range of areas, including endocrinology, metabolism, arteriosclerosis, nutrition, musculoskeletal system, and sensory organs. Furthermore, it is not limited to the elderly, but targets people of all ages, with the goal of extending the time they can live healthily with youthful physical functions beyond their current age.

[0005] Generally, aging is understood as a phenomenon in which the number of cells decreases with age, leading to a decline in physical, physiological, and mental functions. Physical changes due to aging begin after reaching maturity, around the age of 40, and include wrinkles, hair and teeth loss, decreased vision and hearing, reduced motor function, and decreased bone density. While aging itself is not a disease, the decline in physical and physiological functions increases the risk of so-called geriatric diseases such as arteriosclerosis, osteoporosis, and cataracts, and the decline in mental functions such as memory and learning also occurs in conjunction with the decline in physical functions.

[0006] In the field of anti-aging medicine, research on aging is progressing in many areas, and as a result, several hypotheses regarding the causes of aging have been proposed, as shown below. However, all of these remain at the hypothesis level, and the full picture has not yet been elucidated. 1) Genetic Program Theory At the ends of chromosomes, which carry genetic information, there are regions called telomeres. These telomeres play a role in correctly copying and passing on genetic information during cell division. However, they shorten with each cell division, and when they become too short, telomere dysfunction occurs, which is thought to reduce cell regeneration and impair tissue function. In other words, telomeres limit the number of cell divisions, and when cell division becomes impossible, the body's activity inevitably declines, leading to aging. 2) DNA damage theory It is believed that aging occurs when DNA is damaged by stimuli such as ultraviolet rays and air pollutants, and cell division occurs before this damage can be repaired, resulting in the accumulation of damaged and deteriorated information. While damaged DNA is repaired at a constant rate, this repair rate decreases with age. 3) Reactive Oxygen Species Theory It is believed that some oxygen that is not used in the body becomes reactive oxygen species, which oxidize cells. When oxidized cells are unable to function normally, this is thought to accelerate aging. Factors that increase the generation of reactive oxygen species include exposure to ultraviolet light, stress, smoking, polluted environments, and a diet high in fat and additives. 4) Hormone theory It is believed that aging progresses as the secretion of certain hormones, such as growth hormone (which is involved in controlling metabolism), melatonin (which is involved in sleep), and sex hormones (which are involved in reproduction in both men and women), decreases in proportion to age, resulting in a loss of the physiological functions of these hormones. 5) Immune function theory It is believed that as we age, our immune function against foreign pathogens declines, and we develop a tendency towards excessive inflammatory responses, leading to a decline in metabolism and cell regeneration, and accelerating aging. The reason for the decline in immune function with age is linked to thymic atrophy. The thymus is a central organ where T cells differentiate and proliferate, and where immune responses are expressed, but it is known to atrophy with age.

[0007] Previous research suggests that improving daily lifestyle habits, maintaining a balanced diet, and getting moderate exercise are important for slowing the aging process and maintaining a youthful, healthy state. Regarding diet, in recent years, food components that are considered effective in preventing aging have become more widely known. For example, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and B vitamins (B6, B) are known to prevent brain aging. 12 , folic acid, lecithin, choline, tryptophan; as food ingredients that boost immunity, vitamin A, vitamin E, vitamin C, vitamin B group (pantothenic acid, B6, B) 12Foods known to increase bone mass include calcium, protein, vitamin D, and vitamin K; foods known to remove reactive oxygen species include carotenoids (lycopene, lutein, vitamin A, etc.), astaxanthin, polyphenols (flavonoids, catechins, isoflavones, sesamin, curcumin, etc.), vitamin E, vitamin C, and coenzyme Q. On the other hand, enzymes known to eliminate reactive oxygen species include superoxide dismutase (SOD), glutathione peroxidase, and catalase.

[0008] In recent years, new anti-aging agents have also been developed to prevent aging. For example, an anti-aging agent has been reported that can prevent skin aging, particularly improving skin pigment deposition, and contains (A) at least one selected from the group consisting of ascorbic acid 2-glucoside and its salts, and (B) at least one selected from the group consisting of adenine, adenosine, adenosine 2'-monophosphate, adenosine 3'-monophosphate, adenosine 5'-monophosphate, cyclic adenosine 3',5'-monophosphate, adenosine 5'-diphosphate, adenosine 5'-triphosphate, and salts thereof (Patent Document 1).

[0009] As another example, an anti-aging agent has been reported that is characterized by containing an extract obtained by extracting the brown alga Sargassum horneri (Sargassum horneri) with water and then enzymatically treating it with cellulase in the extraction process, as an active ingredient (Patent Document 2). [Prior art documents] [Patent Documents]

[0010] [Patent Document 1] Patent No. 4129574 [Patent Document 2] Patent No. 4926448 [Overview of the Initiative] [Problems that the invention aims to solve]

[0011] The present invention aims to provide an anti-aging agent and method that are effective in suppressing the progression of aging and restoring youthfulness, and that are safe even when ingested over a long period of time. [Means for solving the problem]

[0012] As a result of diligent research to solve the above problems, the inventors of the present invention discovered that nicotinamide mononucleotide, an intermediate metabolite involved in the biosynthesis of the coenzyme NAD (nicotinamide adenine dinucleotide), has excellent anti-aging effects, and thus completed the present invention.

[0013] The present invention is as follows: [1] An anti-aging agent containing nicotinamide mononucleotide as its active ingredient. [2] An anti-aging agent as described in [1], for the improvement of signs of skin aging, dry skin, skin spots, freckles, or rough skin. [3] The anti-aging agent described in [1], which is used to improve hormone secretion. [4] The anti-aging agent according to [3], wherein the hormone is one or more selected from growth hormone, ghrelin, thyroid-stimulating hormone, thyroid hormone, adrenocorticotropic hormone, adrenocortical hormone, sex hormone, prolactin, antidiuretic hormone, parathyroid hormone, calcitonin, and melatonin. [5] An anti-aging agent as described in [1], for reducing reactive oxygen species in the body. [6] Anti-aging agent is a food for preventing aging, an anti-aging agent as described in any of [1] to [5]. [7] An anti-aging agent is a pharmaceutical product for preventing aging, as described in any of [1] to [5]. [8] An anti-aging method (excluding medical procedures for humans) characterized by administering an effective amount of nicotinamide mononucleotide to a subject in need of it. [Effects of the Invention]

[0014] The present invention has an excellent anti-aging effect and is safe because it contains nicotinamide mononucleotide, an intermediate metabolite involved in the biosynthesis of NAD in vivo, and can be ingested over a long period of time. + It is safe because it contains nicotinamide mononucleotide, an intermediate metabolite involved in the biosynthesis of NAD in vivo, and can be ingested over a long period of time.

Brief Description of the Drawings

[0015] [Figure 1] It is an explanatory diagram showing the metabolic pathway involving niacin (a general term for nicotinamide and nicotinic acid). [Figure 2a] It is a graph showing the change in melatonin blood concentration of the entire group of subjects when nicotinamide mononucleotide was orally administered to the subjects over 24 weeks. [Figure 2b] It is a graph showing the change in melatonin blood concentration of male subjects when nicotinamide mononucleotide was orally administered to the subjects over 24 weeks. [Figure 2c] It shows the change in melatonin blood concentration of female subjects when nicotinamide mononucleotide was orally administered to the subjects over 24 weeks. [Figure 3a] It is a graph showing the change rate (%) of melatonin blood concentration up to 24 weeks of the entire group of subjects when nicotinamide mononucleotide was orally administered to the subjects over 24 weeks. [Figure 3b] It is a graph showing the change rate (%) of melatonin blood concentration up to 24 weeks of male subjects when nicotinamide mononucleotide was orally administered to the subjects over 24 weeks. [Figure 3c] It is a graph showing the change rate (%) of melatonin blood concentration up to 24 weeks of female subjects when nicotinamide mononucleotide was orally administered to the subjects over 24 weeks. [Figure 4a] It is a graph showing the change in growth hormone blood concentration of the entire group of subjects when nicotinamide mononucleotide was orally administered to the subjects over 24 weeks. [Figure 4b] It is a graph showing the change in growth hormone blood concentration of male subjects when nicotinamide mononucleotide was orally administered to the subjects over 24 weeks. [Figure 4c] This figure shows the changes in blood growth hormone levels in female subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 5a] This graph shows the percentage change in growth hormone blood concentration in all subjects up to 24 weeks after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 5b] This graph shows the percentage change in growth hormone blood concentration in male subjects up to 24 weeks after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 5c] This graph shows the percentage change in growth hormone blood concentration in female subjects up to 24 weeks after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 6a] This figure shows the changes in ghrelin blood concentration in all subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 6b] This graph shows the changes in ghrelin blood concentration in male subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 6c] This figure shows the changes in ghrelin blood concentration in female subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 7a] This graph shows the percentage change in ghrelin blood concentration in all subjects up to 24 weeks after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 7b] This graph shows the percentage change in ghrelin blood concentration up to 24 weeks in male subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 7c] This graph shows the percentage change in ghrelin blood concentration up to 24 weeks in female subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 8a]This figure shows the changes in thyroid-stimulating hormone (THS) blood concentration in all subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 8b] This figure shows the changes in thyroid-stimulating hormone (THS) blood levels in male subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 8c] This figure shows the changes in thyroid-stimulating hormone (THS) blood levels in female subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 9a] This figure shows the percentage change in thyroid-stimulating hormone (THS) blood concentration in all subjects up to 24 weeks after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 9b] This figure shows the percentage change in thyroid-stimulating hormone (THS) blood concentration up to 24 weeks in male subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 9c] This figure shows the percentage change in thyroid-stimulating hormone (THS) blood concentration up to 24 weeks in female subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 10a] This figure shows the changes in free thyroxine blood concentration across all subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 10b] This figure shows the changes in free thyroxine blood concentration in male subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 10c] This figure shows the changes in free thyroxine blood concentration in female subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 11a] This figure shows the percentage change in free thyroxine blood concentration in all subjects up to 24 weeks after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 11b]This figure shows the percentage change in free thyroxine blood concentration up to 24 weeks in male subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 11c] This figure shows the percentage change in free thyroxine blood concentration up to 24 weeks in female subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 12a] This figure shows the changes in parathyroid hormone blood concentration in all subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 12b] This figure shows the changes in parathyroid hormone blood concentration in male subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 12c] This figure shows the changes in parathyroid hormone blood concentration in female subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 13a] This figure shows the percentage change in parathyroid hormone blood concentration in all subjects up to 24 weeks after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 13b] This figure shows the percentage change in parathyroid hormone blood concentration up to 24 weeks in male subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 13c] This figure shows the percentage change in parathyroid hormone blood concentration up to 24 weeks in female subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 14a] This figure shows the changes in estradiol blood concentration across all subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 14b] This figure shows the changes in estradiol blood concentration in male subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 14c]This figure shows the changes in estradiol blood concentration in female subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 15a] This figure shows the percentage change in estradiol blood concentration in all subjects up to 24 weeks after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 15b] This figure shows the percentage change in estradiol blood concentration up to 24 weeks in male subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 15c] This figure shows the percentage change in estradiol blood concentration up to 24 weeks in female subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 16a] This graph shows the changes in testosterone blood concentration across all subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 16b] This graph shows the changes in testosterone blood levels in male subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 16c] This graph shows the changes in testosterone blood levels in female subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 17a] This graph shows the percentage change in testosterone blood concentration in all subjects up to 24 weeks after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 17b] This graph shows the percentage change in testosterone blood concentration (%) up to 24 weeks in male subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 17c] This graph shows the percentage change in testosterone blood concentration (%) up to 24 weeks in female subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 18a]This figure shows the changes in prolactin blood concentration in all subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 18b] This graph shows the changes in prolactin blood concentration in male subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 18c] This graph shows the changes in prolactin blood concentration in female subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 19a] This figure shows the percentage change in prolactin blood concentration in all subjects up to 24 weeks after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 19b] This graph shows the percentage change in prolactin blood concentration (%) up to 24 weeks in male subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 19c] This graph shows the percentage change in prolactin blood concentration up to 24 weeks in female subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 20a] This figure shows the changes in adrenocorticotropic hormone (ACTH) blood concentration in all subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 20b] This figure shows the changes in adrenocorticotropic hormone (ACTH) blood concentration in male subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 20c] This figure shows the changes in adrenocorticotropic hormone (ACTH) blood concentration in female subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 21a] This figure shows the percentage change in adrenocorticotropic hormone (ACTH) blood concentration in all subjects up to 24 weeks after oral administration of nicotinamide mononucleotide to the subjects over a 24-week period. [Figure 21b]This figure shows the percentage change in adrenocorticotropic hormone (ACTH) blood concentration up to 24 weeks in male subjects who received oral administration of nicotinamide mononucleotide for 24 weeks. [Figure 21c] This figure shows the percentage change in adrenocorticotropic hormone (ACTH) blood concentration up to 24 weeks in female subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 22a] This graph shows the changes in cortisol blood concentration across all subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 22b] This graph shows the changes in cortisol blood concentration in male subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 22c] This graph shows the changes in cortisol blood concentration in female subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 23a] This figure shows the percentage change in cortisol blood concentration in all subjects up to 24 weeks after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 23b] This graph shows the percentage change in cortisol blood concentration (%) up to 24 weeks in male subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 23c] This graph shows the percentage change in cortisol blood concentration up to 24 weeks in female subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 24a] This graph shows the changes in calcitonin blood concentration in all subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 24b] This graph shows the changes in calcitonin blood concentration in male subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 24c]This graph shows the changes in calcitonin blood concentration in female subjects after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 25a] This figure shows the percentage change in calcitonin blood concentration in all subjects up to 24 weeks after oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 25b] This graph shows the percentage change in calcitonin blood concentration up to 24 weeks in male subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Figure 25c] This figure shows the percentage change in calcitonin blood concentration up to 24 weeks in female subjects who received oral administration of nicotinamide mononucleotide over 24 weeks. [Modes for carrying out the invention]

[0016] The anti-aging agent according to the present invention contains nicotinamide mononucleotide as an active ingredient and exhibits an anti-aging effect. In the present invention, "anti-aging" broadly includes not only the prevention of aging in the narrow sense, but also the improvement of aging phenomena, the delay of aging, rejuvenation, etc., and includes all aspects of preventing, improving, delaying, rejuvenating, and normalizing the decline of physical, physiological, and mental functions associated with aging. Specifically, for example, it includes symptoms of skin aging (wrinkles, sagging, loss of skin elasticity, etc.), dry skin due to aging (decreased skin moisture retention), skin spots, freckles, rough skin, hormones (growth hormone, ghrelin, methionine, methicillin). This refers to the effects of preventing, improving, or delaying the decrease or increase in the secretion of hormones (such as gonadotropin-releasing hormone, thyroid hormone, adrenocorticotropic hormone, adrenocortical hormone, sex hormones, prolactin, antidiuretic hormone, parathyroid hormone, calcitonin, melatonin, etc.), damage to cells (brain cells, cardiomyocytes, etc.) caused by reactive oxygen species, hair and tooth loss, decreased vision and hearing, decreased motor function, decreased bone mass, decreased physical strength, decreased memory, decreased learning ability, decreased immune function, and the onset of geriatric diseases. The detailed reasons why such effects can be obtained by using nicotinamide mononucleotide as the active ingredient are currently under investigation, but NAD+ One of the main reasons for this is thought to be that nicotinamide mononucleotide promotes "sirtuins," represented by the glucose-dependent deacetylases Sirt1 and Sirt3, and as a result normalizes glucose tolerance and hormone secretion systems such as growth hormone and cortisol. The present invention will be described in detail below.

[0017] Nicotinamide mononucleotide (Chemical formula: C 11 H 15 N2O8P) is a compound represented by the following structural formula [Chemical Formula 1] that is produced in the bodies of many organisms, including humans. It is commonly called NMN (Nicotinamide mononucleotide) and acts as a coenzyme NAD. + It is known as an intermediate metabolite involved in the biosynthesis of [substance name].

[0018] [ka]

[0019] Nicotinamide mononucleotide, the active ingredient in the aforementioned anti-aging agent, is produced in the body by the liver tissue in the NAD metabolic pathway, specifically the pathway involved in the synthesis of nicotinamide adenine dinucleotide (NAD) from quinolinic acid via the kynurenine pathway. This point will be explained in detail with reference to Figure 1. Figure 1 is an explanatory diagram showing the metabolic pathway involved in niacin (a collective term for nicotinamide and nicotinic acid), also known as vitamin B3. Nicotinic acid ingested from food is taken up by the liver and converted to nicotinamide, which is then supplied to the entire body via the bloodstream. Each cell takes in nicotinamide from the blood and converts it to NAD and NADP for use. Nicotinamide is also biosynthesized from tryptophan.

[0020] As shown in Figure 1, in vivo, when tryptophan is used as a starting material, it is converted to quinolinic acid (QA) via the kynurenine pathway, which is the tryptophan metabolic pathway, and then to nicotinic acid mononucleotide (NaMN). On the other hand, when nicotinic acid (Na) is used as a starting material, nicotinic acid is directly converted to NaMN. NaMN is then interconverted to NAD, nicotinamide (NaM), and nicotinamide mononucleotide via the NAD cycle, through nicotinic acid adenine dinucleotide (NaAD). Nicotinamide (NaM) is converted to nicotinamide mononucleotide by nicotinamide phosphoribosyltransferase (NAMPT), and then nicotinamide mononucleotide is converted to NAD by nicotinamide mononucleotide adenyltransferase (NMNAT). Nicotinamide mononucleotide is also produced from nicotinamide riboside (NR), an intermediate metabolite of NAD.

[0021] Nicotinamide mononucleotide exists as two optical isomers, the α-isomer and the β-isomer, but the β-isomer is used in this invention. Nicotinamide mononucleotide can be obtained, for example, by synthesizing nicotinamide riboside from nicotinamide and ribose (see Bioorg. Med. Chem. Lett., 12, 1135-1137 (2002)), and then phosphorylating the hydroxyl group at position 5 of the ribose moiety (see Chem. Comm., 1999, 729-730). Specifically, for example, first, nicotinamide and L-ribose tetraacetate are dissolved in anhydrous acetonitrile, an excess amount of trimethylsilyltrifluorosulfonic acid is added under a nitrogen atmosphere, the mixture is stirred at room temperature, and methanol is added to stop the reaction. The reaction solution is then passed through a column packed with activated carbon, washed with distilled water, and the product is recovered by elution with methanol. Next, to carry out the phosphorylation reaction of the hydroxyl group at position 5 of the L-ribose moiety of this product, the above product is dissolved in trimethoxyphosphate, phosphorus oxychloride is added dropwise under ice cooling, the mixture is stirred under a nitrogen stream, and an aqueous sodium hydroxide solution is added to neutralize it and stop the reaction. Then, a cold acetonitrile-ether solution is added to the reaction mixture. After that, the lower layer (aqueous phase) is passed through an anion exchange resin to recover the reaction product, and further purification with a cation exchange resin allows for the recovery of highly pure nicotinamide mononucleotide. Nicotinamide mononucleotide is commercially available, and these commercially available products can be purchased and used.

[0022] The nicotinamide mononucleotide is a purified product with a low impurity content, and its purity is preferably 90% or higher, and more preferably 95% or higher. If the purity is less than 90%, an off-odor may be generated, or the effect of the nicotinamide mononucleotide may be weakened, potentially preventing the full effect of the present invention from being obtained.

[0023] As described above, the purity of nicotinamide mononucleotide is preferably 90% or more, and the purity (mass ratio) is defined as the value obtained by subtracting impurities other than nicotinamide mononucleotide from 100% on an anhydrous basis. Therefore, the purity of nicotinamide mononucleotide can be determined by the formula: purity of nicotinamide mononucleotide (%) = 100 - impurities other than nicotinamide mononucleotide (%). Here, examples of such impurities include metabolites other than nicotinamide mononucleotide involved in the NAD metabolic pathway, particularly nicotinamide and nicotinamide adenine dinucleotide, as shown in FIG. 1. If there are impurities such as the above metabolites involved in the NAD metabolic pathway in the nicotinamide mononucleotide used in the present invention, the uptake of nicotinamide mononucleotide into living cells may decrease, and as a result, the effect of the present invention may be attenuated. The quantification of the above impurities involved in the NAD metabolic pathway is performed by injecting a test solution of dried nicotinamide mononucleotide powder into an HPLC apparatus, determining the peak area of the obtained chromatograph, and using an absolute calibration curve method with a standard sample (vertical axis: peak area, horizontal axis: concentration). In the case of trace substances, the peak height can be used for accurate quantification, so it is appropriately selected according to the characteristics of the apparatus used. The identification of the separated substances is performed based on the retention time.

[0024] The anti-aging agent according to the present invention can be easily produced by using nicotinamide mononucleotide alone or by mixing other components. Other components are not particularly limited as long as the effects of the present invention are achieved.

[0025] Examples of other components include, as described above, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), vitamin B group (B6, B 12 , folic acid), lecithin, choline, tryptophan; vitamin A, vitamin E, vitamin C, vitamin B group (pantothenic acid, B6, B 12Examples of food components that increase bone mass include folic acid, zinc, calcium, protein, vitamin D, and vitamin K; and carotenoids (lycopene, lutein, vitamin A, etc.), astaxanthin, polyphenols (flavonoids, catechins, isoflavones, sesamin, curcumin, etc.), vitamin E, vitamin C, and coenzyme Q, which are known to remove reactive oxygen species. In addition, other components that are commonly used as auxiliary ingredients in the food industry, such as various vitamins, trace elements, citric acid, malic acid, flavorings, and inorganic salts, may also be included.

[0026] In the present invention, resveratrol is mentioned as another component particularly effective in enhancing its anti-aging effect. Resveratrol is known as an antioxidant found in grape skins, red wine, peanut skins, Japanese knotweed, and gnemon. Resveratrol includes resveratrol derivatives such as trans and cis isomers, trans-cis isomer mixtures, dimers, and methylated resveratrol. Trans isomers, which are usually stable to heat, are used in health foods and the like. Resveratrol may be prepared by extraction and purification from any source material, or it may be prepared synthetically.

[0027] While the ratio of resveratrol and nicotinamide mononucleotide is not limited, from the viewpoint of maximizing the effects of the present invention, it is preferable to adjust the ratio so that, in the daily intake for adults, the amount of resveratrol is 1 to 100 parts by mass and the amount of nicotinamide mononucleotide is 1 to 25 parts by mass.

[0028] The anti-aging agent according to the present invention is primarily taken orally to prevent aging. In the present invention, "anti-aging" has a broad meaning, as described above, and includes not only the prevention of aging in the narrow sense, but also the improvement of aging phenomena, the delay of aging, rejuvenation, etc., and therefore includes everything such as the prevention, improvement, delay, rejuvenation, and normalization of the decline of physical functions, physiological functions, and mental functions that accompany aging. Specifically, for example, it includes the occurrence of aging symptoms of the skin (wrinkles, sagging, loss of skin elasticity, etc.), dry skin due to aging (decreased skin moisture retention), the occurrence of skin spots, freckles, rough skin, hormones (growth hormone, etc.) It can be said that it has preventive, ameliorative, or delayed effects on the following: decreased or increased secretion of ghrelin, thyroid-stimulating hormone, thyroid hormone, adrenocorticotropic hormone, adrenocortical hormone, sex hormone, prolactin, antidiuretic hormone, parathyroid hormone, calcitonin, melatonin, etc.; damage to cells (brain cells, cardiomyocytes, etc.) by reactive oxygen species; hair and tooth loss; decreased vision and hearing; decreased motor function; decreased bone mass; decreased physical strength; decreased memory; decreased learning ability; decreased immune function; and the onset of geriatric diseases.

[0029] The anti-aging agent according to the present invention is effective against skin aging symptoms, dry skin due to aging (decreased skin moisture retention), skin spots, freckles, and rough skin. Here, "skin aging symptoms" refer mainly to the occurrence of wrinkles, sagging, and loss of skin firmness due to the decrease in skin elasticity associated with aging. The reason why the present invention prevents and improves skin aging symptoms is thought to be that nicotinamide mononucleotide activates weakened skin metabolic function, promotes collagen production, and reduces reactive oxygen species, as will be described later.

[0030] The anti-aging agent according to the present invention can be used to moisturize the skin of the face, hands, etc., and to improve dry skin by continuously improving the skin's moisturizing properties. By applying the present invention, the amount of water in the skin increases, and as a result of improved skin moisturizing properties, dryness, firmness, elasticity, and flexibility of the skin are improved. The reason why the present invention brings about improved skin moisturizing properties is thought to be that nicotinamide monofurecreotide influences the increased production of natural moisturizing factors and intercellular lipids in keratinocytes, and promotes hyaluronic acid production.

[0031] The anti-aging agent according to the present invention can be used to prevent the production and deposition of melanin associated with aging, and to obtain a whitening effect that prevents or improves skin blemishes and freckles. The reason why the present invention provides a whitening effect is thought to be that nicotinamide mononucleotide promotes the excretion of melanin, among other things.

[0032] The anti-aging agent according to the present invention can be used to prevent and improve skin roughness associated with aging. Depending on the cause of the skin roughness, it is more effective to appropriately combine anti-inflammatory agents, vitamins, hormones, plant extracts, disinfectants, oily components, etc. The reason why the present invention provides a preventive and ameliorative effect on skin roughness is thought to be that nicotinamide mononucleotide enhances the activity of sirtuins in skin tissue.

[0033] Furthermore, the anti-aging agent according to the present invention improves the secretion of one or more hormones selected from several hormones (primarily hormones whose secretion decreases in proportion to age), specifically, for example, growth hormone, ghrelin, thyroid-stimulating hormone, thyroid hormone, adrenocorticotropic hormone, adrenocortical hormone, sex hormone, prolactin, antidiuretic hormone, parathyroid hormone, calcitonin, and melatonin, thereby rejuvenating the physiological effects brought about by each of these hormones and thereby exerting an anti-aging effect. Therefore, the anti-aging agent according to the present invention can be used for the purpose of improving the secretion of these hormones. Note that "improvement of hormone secretion" means promoting or suppressing the amount of hormone secretion to direct the amount of hormone secretion in an appropriate direction.

[0034] Growth hormone is a hormone primarily secreted from the pituitary gland in the hypothalamus. By being secreted into target organs, it promotes the growth of those organ tissues and also controls metabolism. Also known as the "rejuvenation hormone," its basal secretion and responsiveness decline with age. Possible mechanisms for this decline include a decrease in growth hormone-secreting cells, a decrease in production, decreased responsiveness to growth hormone-releasing hormone, increased sensitivity of growth hormone-secreting cells to insulin-like growth factor (IGF-1), hypothalamic growth hormone-releasing hormone deficiency, and increased somatostatin secretion. In adults, growth hormone is considered to play an important role in maintaining the sense of health that healthy individuals normally experience. In addition, it is said to have effects such as improving memory, preventing fatigue and mood swings, promoting bone density, maintaining reproductive function, strengthening immune function, promoting fat burning, and promoting muscle growth.

[0035] Ghrelin is a hormone secreted from the stomach and has a variety of physiological effects, including growth hormone secretion-promoting activity, appetite-stimulating effect, gastrointestinal motility-promoting effect, cardiovascular protective effect, and anti-inflammatory effect.

[0036] Thyroid-stimulating hormone (SMO) is a hormone secreted by SMO cells in the anterior pituitary gland, which acts on the thyroid gland to stimulate the secretion of thyroid hormones.

[0037] Thyroid hormones are hormones secreted by the thyroid gland, and two types are known: thyroxine (T4) and triiodothyronine (T3). They generally act on cells throughout the body, increasing the metabolic rate of cells. It is known that with age, the function of the thyroid gland itself declines, and the responsiveness of thyroid-stimulating hormone (TSH) to thyroid hormone-releasing hormone (TRH) decreases, leading to a decrease in the secretion of triiodothyronine. Specifically, it is said to have effects such as improving skin moisture retention, improving memory, preventing fatigue and mood swings, preventing middle-age weight gain, preventing sensitivity to cold, and preventing hair loss.

[0038] Prolactin is a hormone primarily secreted by prolactin-secreting cells in the anterior pituitary gland. In women, prolactin levels are said to decrease around menopause due to a decline in estrogen.

[0039] Adrenocorticotropic hormone (ACTH) is a hormone secreted from the anterior pituitary gland that acts on the adrenal cortex, promoting the secretion of adrenal cortical hormones such as glucocorticoids.

[0040] Adrenocortical hormones are hormones secreted from the adrenal cortex, which is divided into the zona glomerulosa, zona fasciculata, and zona reticularis. Mineralocorticoids (such as aldosterone) are produced from the zona glomerulosa, glucocorticoids (such as cortisol) from the zona fasciculata, and adrenal androgens from the zona reticularis. Adrenocortical hormones have many physiological effects, including anti-inflammatory, immunosuppressive, anti-stress, water and electrolyte regulation, glucose metabolism, lipid metabolism, anabolic and anabolic inhibitory effects, blood coagulation promotion, and pituitary suppression. Androgens are a general term for male hormones, and the biological activity of adrenal androgens as male hormones is weaker than that of testosterone secreted from the testes.

[0041] Sex hormones are broadly classified into male hormones, which are mainly produced by the interstitial cells of the testes, and female hormones, which are secreted by the ovaries. Male hormones enhance so-called male characteristics. Their secretion peaks between the ages of 20 and 30, and then gradually declines. The most representative male hormone is testosterone. Male hormones play a role in maintaining bone and muscle strength, maintaining sexual function, maintaining the condition of blood vessels, preventing arteriosclerosis, and preventing metabolic syndrome. On the other hand, there are two types of female hormones: estrogen, which creates femininity, and progesterone, which helps in pregnancy. The most representative estrogen is estradiol. Women enter menopause around the age of 50, when the secretion of female hormones decreases sharply, and symptoms of so-called autonomic nervous system dysfunction (hot flashes, sweating, fatigue, dizziness, etc.) appear.

[0042] Prolactin is a hormone primarily secreted from the anterior pituitary gland. It has several functions, including promoting mammary gland development, stimulating milk production and secretion, suppressing gonads, maintaining luteal phase function, promoting endometrial proliferation, regulating water and electrolyte balance, and stimulating the immune system. Due to estrogen levels, prolactin levels in women are said to decrease around the time of menopause.

[0043] Antidiuretic hormone (AHH) is a hormone secreted from the posterior pituitary gland that acts on the renal tubules to concentrate urine and help the body retain water. As kidney function declines with age, the ability to concentrate urine decreases, resulting in the excretion of large amounts of dilute urine, making it difficult for the body to retain water. AHH helps prevent this situation. In elderly people, the amount of AHH secreted decreases, which can lead to frequent urination, urinary incontinence, and nocturia (frequent nighttime urination).

[0044] Parathyroid hormone is a hormone secreted by the parathyroid gland and, along with calcitonin and vitamin D secreted by the thyroid gland, plays a role in maintaining a constant calcium concentration in the blood and body fluids. As we age, calcium absorption decreases, which leads to a persistent overproduction of parathyroid hormone. This overproduction is said to cause increased bone resorption, where osteoclasts break down old bone, and an increased bone turnover rate, resulting in osteoporosis, one of the diseases of old age.

[0045] Calcitonin is a hormone secreted from parafollicular cells of the thyroid gland. Its secretion is promoted by an increase in blood calcium levels and suppressed when calcium levels decrease.

[0046] Melatonin is a hormone secreted from the pineal gland in the brain and is also known as the "sleep hormone." It is involved in the biological rhythms of living organisms and influences a person's sleep-wake cycle. It has a calming effect on the nerves at night and promotes sleep. Its secretion is highest at night and stops when a person is awake, showing a diurnal variation. Melatonin is secreted most abundantly in infancy, and its secretion decreases with age, with little increase in nighttime melatonin observed after the age of 60. As melatonin secretion decreases with age, the amount of sleep shortens, causing sleep disorders, which are common in the elderly. In addition to inducing sleep, melatonin is also attracting attention as a hormone that is effective in preventing aging because of its antioxidant effects, which promote cell metabolism and relieve fatigue. Furthermore, melatonin acts on the functions of various physiologically active substances such as neurotransmitters, hormones, and cytokines, and acts as a biological response modifier that controls the nervous and immune systems, regulating many biological functions. This regulation acts in a direction that prevents aging.

[0047] Furthermore, the anti-aging agent according to the present invention reduces reactive oxygen species (superoxide, hydrogen peroxide, and hydroxyl radicals), which are considered one of the causes of aging, thereby protecting cells from reactive oxygen species and contributing to anti-aging. Therefore, the anti-aging agent according to the present invention can be used for the purpose of reducing reactive oxygen species. In living organisms, the skin in particular is prone to generating reactive oxygen species when exposed to ultraviolet rays; therefore, reducing reactive oxygen species is considered one of the reasons for the anti-aging effect on the skin, as mentioned above. While the mechanism by which the anti-aging agent according to the present invention reduces reactive oxygen species is still under investigation, it is thought that it exerts its effect by activating Sirt1, etc., thereby enhancing the antioxidant function within cells.

[0048] The method for manufacturing the aforementioned anti-aging agent is not particularly limited, and a general manufacturing method used for its production can be appropriately selected depending on its form. For example, if the form is a powder, it can be manufactured by uniformly kneading nicotinamide mononucleotide and other components as needed. The active ingredient, nicotinamide mononucleotide, is available on the market and can be commercially obtained. In particular, quality control and mass production systems for nicotinamide mononucleotide have been established in recent years.

[0049] The anti-aging agent according to the present invention can be used as a food or a pharmaceutical. When used as a food, the anti-aging agent can be provided in the food sector as an anti-aging food. When consumed daily in the form of food, the anti-aging effect is continuously exerted, making it particularly effective in preventing aging. The types of foods to which the present invention applies are not particularly limited, and include not only general foods, but also functional foods, foods for specified health uses, nutritional supplements, food additives, animal feed, nursing care foods, therapeutic diets, diet foods, etc. Specifically, examples include confectionery (gum, candy, cookies, gummies, biscuits, cakes, chocolates, Japanese sweets, jelly, etc.), bread, noodles, processed rice and grain products (cereals, etc.), processed meat products, processed seafood products, processed vegetables, prepared foods, fermented foods, seasonings (sauces, dressings, ketchup, etc.), spices, dairy products (yogurt, cheese, milk, etc.), ice cream, frozen foods, retort foods, beverages (carbonated drinks, soft drinks, dairy drinks, alcoholic beverages, sports drinks, fruit juices, teas, nutritional drinks, concentrated beverages, etc.), and powdered beverages (powdered juices, powdered soups, etc.). Furthermore, the form of the aforementioned foods is not limited, and especially in the case of functional foods and foods for specified health uses, they can be processed and provided as, for example, powders, tablets, pills, granules, hard capsules, soft capsules, jellies, liquids, pastes, etc.

[0050] The amount of the aforementioned food to be consumed varies depending on the type of food, the age, sex, weight of the person consuming it, the expected effects, symptoms, etc. However, the daily intake of nicotinamide mononucleotide contained in the food for adults is usually 1 mg to 500 mg, preferably 5 mg to 250 mg, and more preferably 50 mg to 200 mg. If the intake is less than 1 mg, the effects of the present invention may not be obtained, while if the intake is more than 500 mg, the effects obtained will not change significantly, making it economically disadvantageous. The proportion of nicotinamide mononucleotide in the aforementioned food can be appropriately set within a range of 100% or less of the total weight of the food.

[0051] Since the aforementioned food is safe and shows no particular side effects, it can be consumed over a long period of time for anti-aging purposes. It can be used not only by the elderly but also by young people.

[0052] On the other hand, the anti-aging agent according to the present invention can be administered orally or parenterally in the pharmaceutical field as a pharmaceutical product (including quasi-drugs) for anti-aging purposes. The dosage form of the pharmaceutical product is not particularly limited, but examples include orally administered preparations such as powders, tablets, sustained-release tablets, chewable tablets, effervescent tablets, lozenges, buccal tablets, sublingual tablets, capsules, granules, pills, dry syrups, liquids, suspensions, syrups, and elixirs, as well as injectable preparations, intravenous solutions, suppositories, and topical preparations. Of these, orally administered preparations such as powders, tablets, and capsules are preferred considering ease of administration and the stability of the active ingredient.

[0053] The aforementioned pharmaceuticals may be appropriately formulated with pharmaceutically acceptable known excipients suitable for their dosage form, taking into consideration their physicochemical and biological properties. Examples of such excipients include excipients (lactose, starch, crystalline cellulose, sodium phosphate, etc.), solvents (water, soybean oil, saline solution, non-aqueous solvents for injection, etc.), binders (starch, gelatin, acacia gum, sodium alginate, carmellose sodium, methylcellulose, ethylcellulose, hydroxypropyl methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, etc.), disintegrants (starch, carmellose sodium, etc.), lubricants (talc, magnesium stearate, calcium stearate, macrogol, sucrose fatty acid esters, etc.), coating agents (sucrose, HPC, shellac, gelatin, glycerin, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, etc.), and stabilizers (sodium bisulfite, sodium thiosulfate, sodium edetate, sodium citrate, ascorbic acid, dibutylhydroxypropyl methylcellulose). (e.g., Luen), preservatives (methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, benzyl alcohol, phenol, chlorobutanol, benzalkonium chloride, benzethonium chloride, sodium dehydroacetate, thimerosal, etc.), thickeners (methylcellulose, carmellose sodium, chondroitin sulfate, sodium alginate, etc.), suspending agents (various nonionic surfactants, methylcellulose, carmellose sodium, etc.), Examples of additives include emulsifiers (such as gum arabic, cholesterol, sorbitan sesquioleate, polysorbate 80, and sodium lauryl sulfate), buffering agents (such as citric acid, acetic acid, sodium phosphate, and boric acid), surfactants (such as hydrogenated castor oil and polysorbate 80), colorants (such as water-soluble food colorings and lake colorings), flavoring agents (such as lactose, sucrose, glucose, and mannitol), deodorizing agents (such as aromatic essential oils), and plasticizers (such as phthalates, vegetable oils, and polyethylene glycol).

[0054] The dosage of the aforementioned pharmaceutical product varies depending on the age, weight, symptoms, and frequency of administration of the recipient, and cannot be uniformly prescribed. However, the amount of nicotinamide mononucleotide administered per day to an adult can typically be 1 mg to 500 mg, preferably 5 mg to 250 mg, and more preferably 50 mg to 200 mg. If the dosage is less than 1 mg, the effects of the present invention may not be obtained, while if the dosage is more than 500 mg, the effects obtained do not change significantly, making it economically disadvantageous. The proportion of nicotinamide mononucleotide in the aforementioned pharmaceutical product can be appropriately set according to the dosage form and dosage of the pharmaceutical product.

[0055] The number of times the aforementioned drug is administered can be appropriately determined according to the age, weight, symptoms, and the amount of the drug administered per dose of the patient. An example of the number of times the drug is administered per day is 1 to 3 times.

[0056] As mentioned above, nicotinamide mononucleotide has anti-aging effects. Therefore, the present invention further provides an anti-aging method characterized by administering an effective amount of nicotinamide mononucleotide to a subject that requires it. In other words, it is a method of preventing aging in a subject by administering the anti-aging agent according to the present invention. Preferred subjects for administration are mammals such as humans, mice, rats, rabbits, dogs, cats, cattle, horses, pigs, and monkeys, with humans being particularly preferred. In the above method, the amount of nicotinamide mononucleotide to be administered, the number of times to be administered per day, etc., are as described for the anti-aging agent. Furthermore, the anti-aging agent can be administered at any time and under any circumstances, and can be administered to the subject over a long period of time. [Examples]

[0057] The present invention will be described in more detail below with reference to examples. However, the present invention is not limited to these examples.

[0058] [Examples] Example 1. Evaluation of the melatonin secretion-promoting effect of nicotinamide mononucleotide. To examine the changes in melatonin levels before and after nicotinamide mononucleotide intake, a study was conducted on healthy men and women aged 50-70. For Example 1, we used capsules containing nicotinamide mononucleotide and starch (4 capsules containing 100 mg (low dose) and 200 mg (high dose) of nicotinamide mononucleotide) (manufactured by Shinkowa Pharmaceutical Co., Ltd.). Five healthy men and five healthy women aged 50-70, without any bias in their age range, were given a low dose of the aforementioned capsules, four capsules once daily for 24 weeks (total 10 participants; low-dose group: 100 mg / day). On the other hand, five healthy men and five healthy women aged 50-70, without any bias in their age range, were given a high dose of the aforementioned capsules, four capsules once daily for 24 weeks (total 10 participants; high-dose group: 200 mg / day). To ensure proper evaluation, individuals who regularly take medication for chronic diseases, those taking health foods that may affect clinical research, and those currently participating in other clinical research or trials, or who have participated in other clinical research or trials within the past three months, were excluded from evaluation. The aforementioned capsules were administered orally at 10:00 AM (between meals, on an empty stomach) with water or lukewarm water. Plasma melatonin levels were measured according to standard procedures by an external public institution. Figures 2a-2c show the changes in plasma melatonin concentration (pg / ml) over 24 weeks. Figure 2a shows the changes for all subjects, Figure 2b shows the changes for male subjects, and Figure 2c shows the changes for female subjects. Figures 3a-2c show the percentage change (%) in melatonin blood concentration up to 24 weeks after oral administration of nicotinamide mononucleotide to subjects over 24 weeks. Figure 3a shows the percentage change for all subjects, Figure 3b shows the percentage change for male subjects, and Figure 3c shows the percentage change for female subjects. Furthermore, Table 1 shows the plasma melatonin concentration (pg / ml) before nicotinamide mononucleotide intake (week 0) and after nicotinamide mononucleotide intake (week 24). These values ​​represent the mean ± standard deviation.

[0059] [Table 1]

[0060] 2. Evaluation Results As can be seen from the results shown in Figures 2a-c and 3a-c, nicotinamide mononucleotide intake resulted in a high rate of increase in plasma melatonin concentration. These results confirm the melatonin secretion-promoting effect of oral administration of nicotinamide mononucleotide to middle-aged and elderly men and women, demonstrating its effectiveness in preventing aging. Furthermore, the subjects of the aforementioned evaluation showed no nonspecific symptoms such as abdominal pain, nausea, vomiting, headaches, or bowel irregularities even after 24 weeks of intake, confirming the safety of nicotinamide mononucleotide.

[0061] Example 2. Evaluation of the growth hormone secretion-promoting effect of nicotinamide mononucleotide. To examine the changes in growth hormone levels before and after nicotinamide mononucleotide intake, a study was conducted on healthy men and women aged 50-70. For Example 2, a capsule containing nicotinamide mononucleotide and starch (200 mg of nicotinamide mononucleotide in 4 capsules) (manufactured by Shinkowa Pharmaceutical Co., Ltd.) was used as a sample. Five healthy men and five healthy women aged 50-70 were administered four capsules of the aforementioned capsule formulation once daily for 24 weeks (total of 10 participants; 200 mg / day intake). To ensure proper evaluation, individuals who regularly take medication for chronic diseases, those taking health supplements that may affect clinical research, and those currently participating in other clinical research or trials, or who have participated in other clinical research or trials within the past three months, were excluded from the evaluation. The capsule formulation was administered orally at 10:00 AM (between meals, on an empty stomach) with water or lukewarm water. The amount of growth hormone in plasma was measured by an external public institution according to standard procedures. Figures 4a to 4c show the changes in plasma growth hormone concentration (ng / ml) over 24 weeks. Figure 4a shows the changes for all subjects, Figure 4b shows the changes for male subjects, and Figure 4c shows the changes for female subjects. Figures 5a to 5c show the percentage change (%) in blood growth hormone concentration up to 24 weeks after oral administration of nicotinamide mononucleotide to subjects over 24 weeks. Figure 5a shows the percentage change for all subjects, Figure 5b shows the percentage change for male subjects, and Figure 5c shows the percentage change for female subjects. Furthermore, Table 2 shows the plasma growth hormone concentration (ng / ml) before nicotinamide mononucleotide intake (week 0) and after nicotinamide mononucleotide intake (week 24). These values ​​represent the mean ± standard deviation.

[0062] [Table 2]

[0063] 2. Evaluation Results As can be seen from the results in Figures 4a-c and 5a-c, nicotinamide mononucleotide intake resulted in a high rate of increase in plasma growth hormone concentration. These results confirm that oral administration of nicotinamide mononucleotide to middle-aged and elderly men and women promotes growth hormone secretion, demonstrating its effectiveness in preventing aging. Furthermore, the subjects of the aforementioned evaluation showed no nonspecific symptoms such as abdominal pain, nausea, vomiting, headaches, or bowel irregularities even after 24 weeks of intake, confirming the safety of nicotinamide mononucleotide.

[0064] Example 3. Evaluation of the ghrelin secretion-promoting effect of nicotinamide mononucleotide. To examine the changes in ghrelin levels before and after nicotinamide mononucleotide intake, a study was conducted on healthy men and women aged 50-70. For Example 3, a capsule containing nicotinamide mononucleotide and starch (200 mg of nicotinamide mononucleotide in 4 capsules) (manufactured by Shinkowa Pharmaceutical Co., Ltd.) was used as a sample. Five healthy men and five healthy women aged 50-70 were administered four capsules of the aforementioned capsule formulation once daily for 24 weeks (total of 10 participants; 200 mg / day intake). To ensure proper evaluation, individuals who regularly take medication for chronic diseases, those taking health supplements that may affect clinical research, and those currently participating in other clinical research or trials, or who have participated in other clinical research or trials within the past three months, were excluded from the evaluation. The capsule formulation was administered orally at 10:00 AM (between meals, on an empty stomach) with water or lukewarm water. Plasma ghrelin levels were measured according to standard procedures by an external public institution. Figures 6a-6c show the changes in plasma ghrelin concentration (pg / ml) over 24 weeks. Figure 6a shows the changes for all subjects, Figure 6b shows the changes for male subjects, and Figure 6c shows the changes for female subjects. Figures 7a-7c show the percentage change (%) in ghrelin blood concentration up to 24 weeks after oral administration of nicotinamide mononucleotide to subjects over 24 weeks. Figure 7a shows the percentage change for all subjects, Figure 7b shows the percentage change for male subjects, and Figure 7c shows the percentage change for female subjects. Furthermore, Table 3 shows the plasma ghrelin concentration (pg / ml) before nicotinamide mononucleotide intake (week 0) and after nicotinamide mononucleotide intake (week 24). These values ​​represent the mean ± standard deviation.

[0065] [Table 3]

[0066] 2. Evaluation Results As can be seen from the results in Figures 6a-c and 7a-c, nicotinamide mononucleotide intake resulted in a high rate of increase in plasma ghrelin concentration. These results confirm that oral administration of nicotinamide mononucleotide to middle-aged and elderly men and women promotes ghrelin secretion, demonstrating its effectiveness in preventing aging. Furthermore, the subjects of the aforementioned evaluation showed no nonspecific symptoms such as abdominal pain, nausea, vomiting, headaches, or bowel irregularities even after 24 weeks of intake, confirming the safety of nicotinamide mononucleotide.

[0067] Example 4. Evaluation of the effect of nicotinamide mononucleotide on promoting thyroid-stimulating hormone secretion. To examine the changes in thyroid-stimulating hormone levels before and after nicotinamide mononucleotide ingestion, a study was conducted on healthy men and women aged 50-70. For Example 4, a capsule containing nicotinamide mononucleotide and starch (200 mg of nicotinamide mononucleotide in 4 capsules) (manufactured by Shinkowa Pharmaceutical Co., Ltd.) was used as a sample. Five healthy men and five healthy women aged 50-70 were administered four capsules of the aforementioned capsule formulation once daily for 24 weeks (total of 10 participants; 200 mg / day intake). To ensure proper evaluation, individuals who regularly take medication for chronic diseases, those taking health supplements that may affect clinical research, and those currently participating in other clinical research or trials, or who have participated in other clinical research or trials within the past three months, were excluded from the evaluation. The capsule formulation was administered orally at 10:00 AM (between meals, on an empty stomach) with water or lukewarm water. The amount of thyroid-stimulating hormone (SMO) in plasma was measured by an external public institution according to standard procedures. Figures 8a and 8c show the changes in plasma SMO concentration (μU / ml) over 24 weeks. Figure 8a shows the changes for all subjects, Figure 8b shows the changes for male subjects, and Figure 8c shows the changes for female subjects. Figures 9a and 9c show the percentage change (%) in blood SMO concentration up to 24 weeks after oral administration of nicotinamide mononucleotide to subjects over 24 weeks. Figure 9a shows the percentage change for all subjects, Figure 9b shows the percentage change for male subjects, and Figure 9c shows the percentage change for female subjects. Furthermore, Table 4 shows the values ​​of plasma SMO concentration (μU / ml) before nicotinamide mononucleotide intake (week 0) and after nicotinamide mononucleotide intake (week 24). These values ​​represent the mean ± standard deviation.

[0068] [Table 4]

[0069] 2. Evaluation Results As can be seen from the results shown in Figures 8a-c and 9a-c, nicotinamide mononucleotide intake resulted in a high rate of increase in plasma thyroid-stimulating hormone concentration. These results confirm that oral administration of nicotinamide mononucleotide to middle-aged and elderly men and women promotes thyroid-stimulating hormone secretion, and that nicotinamide mononucleotide is effective in preventing aging. Furthermore, the subjects of the aforementioned evaluation showed no nonspecific symptoms such as abdominal pain, nausea, vomiting, headaches, or bowel irregularities even after 24 weeks of intake, confirming the safety of nicotinamide mononucleotide.

[0070] Example 5. Evaluation of the effect of nicotinamide mononucleotide on promoting free thyroxine (T4) secretion. To confirm the changes in free thyroxine levels before and after nicotinamide mononucleotide ingestion, a study was conducted on healthy men and women aged 50-70 years. For Example 5, a capsule containing nicotinamide mononucleotide and starch (200 mg of nicotinamide mononucleotide in 4 capsules) (manufactured by Shinkowa Pharmaceutical Co., Ltd.) was used as a sample. Five healthy men and five healthy women aged 50-70 were administered a high dose of the aforementioned capsules, four capsules once daily for 24 weeks (total of 10 participants; 200 mg / day intake). To ensure proper evaluation, individuals who regularly take medication for chronic diseases, those taking health supplements that may affect clinical research, and those currently participating in other clinical research or trials, or who have participated in other clinical research or trials within the past three months, were excluded from the evaluation. The capsules were administered orally at 10:00 AM (between meals, on an empty stomach) with water or lukewarm water. The amount of free thyroxine in plasma was measured by an external public institution according to standard procedures. Figures 10a-c show the changes in plasma free thyroxine concentration (ng / dl) over 24 weeks. Figure 10a shows the changes for all subjects, Figure 10b shows the changes for male subjects, and Figure 10c shows the changes for female subjects. Figures 11a-c show the percentage change (%) in free thyroxine blood concentration up to 24 weeks after oral administration of nicotinamide mononucleotide to subjects over 24 weeks. Figure 11a shows the percentage change for all subjects, Figure 11b shows the percentage change for male subjects, and Figure 11c shows the percentage change for female subjects. Furthermore, Table 5 shows the values ​​of plasma free thyroxine concentration (ng / dl) before nicotinamide mononucleotide intake (week 0) and after nicotinamide mononucleotide intake (week 24). These values ​​represent the mean ± standard deviation.

[0071] [Table 5]

[0072] 2. Evaluation Results As can be seen from the results shown in Figures 10a-c and 11a-c, nicotinamide mononucleotide intake resulted in a high rate of increase in plasma free thyroxine concentration. These results confirm that oral administration of nicotinamide mononucleotide to middle-aged and elderly men and women promotes free thyroxine secretion, demonstrating its effectiveness in preventing aging. Furthermore, the subjects of the aforementioned evaluation showed no nonspecific symptoms such as abdominal pain, nausea, vomiting, headaches, or bowel irregularities even after 24 weeks of intake, confirming the safety of nicotinamide mononucleotide.

[0073] Example 6. Evaluation of the parathyroid hormone secretion-promoting effect of nicotinamide mononucleotide. To examine the changes in parathyroid hormone levels before and after nicotinamide mononucleotide intake, a study was conducted on healthy men and women aged 50-70. For Example 6, capsules containing nicotinamide mononucleotide and starch (4 capsules containing 100 mg (low dose) and 200 mg (high dose) of nicotinamide mononucleotide) (manufactured by Shinkowa Pharmaceutical Co., Ltd.) were used as samples. Five healthy men and five healthy women aged 50-70, without any bias in their age range, were given a low dose of the aforementioned capsules, four capsules once daily for 24 weeks (total 10 participants; low-dose group: 100 mg / day). On the other hand, five healthy men and five healthy women aged 50-70, without any bias in their age range, were given a high dose of the aforementioned capsules, four capsules once daily for 24 weeks (total 10 participants; high-dose group: 200 mg / day). To ensure proper evaluation, individuals who regularly take medication for chronic diseases, those taking health foods that may affect clinical research, and those currently participating in other clinical research or trials, or who have participated in other clinical research or trials within the past three months, were excluded from evaluation. The aforementioned capsules were administered orally at 10:00 AM (between meals, on an empty stomach) with water or lukewarm water. The amount of parathyroid hormone in plasma was measured by an external public institution according to standard procedures. Figures 12a-c show the changes in plasma parathyroid hormone concentration (pg / ml) over 24 weeks. Figure 12a shows the changes for all subjects, Figure 12b shows the changes for male subjects, and Figure 12c shows the changes for female subjects. Figures 13a-c show the percentage change (%) in parathyroid hormone blood concentration up to 24 weeks after oral administration of nicotinamide mononucleotide to subjects over 24 weeks. Figure 13a shows the percentage change for all subjects, Figure 13b shows the percentage change for male subjects, and Figure 13c shows the percentage change for female subjects. Furthermore, Table 6 shows the values ​​of plasma parathyroid hormone concentration (pg / ml) before nicotinamide mononucleotide intake (week 0) and after nicotinamide mononucleotide intake (week 24). These values ​​represent the mean ± standard deviation.

[0074] [Table 6]

[0075] 2. Evaluation Results As can be seen from the results shown in Figures 12a-c and 13a-c, nicotinamide mononucleotide intake resulted in a high rate of increase in plasma parathyroid hormone concentration. These results confirm that oral administration of nicotinamide mononucleotide to middle-aged and elderly men and women promotes parathyroid hormone secretion, demonstrating its effectiveness in preventing aging. Furthermore, the subjects of the aforementioned evaluation showed no nonspecific symptoms such as abdominal pain, nausea, vomiting, headaches, or bowel irregularities even after 24 weeks of intake, confirming the safety of nicotinamide mononucleotide.

[0076] Example 7. Evaluation of the effect of nicotinamide mononucleotide on promoting estradiol secretion. To examine the changes in estradiol levels before and after nicotinamide mononucleotide ingestion, a study was conducted on healthy men and women aged 50-70. For Example 7, a capsule containing nicotinamide mononucleotide and starch (100 mg of nicotinamide mononucleotide in 4 capsules) (manufactured by Shinkowa Pharmaceutical Co., Ltd.) was used as a sample. Five healthy men and five healthy women aged 50-70 were administered a high dose of the aforementioned capsules, four capsules once daily for 24 weeks (total of 10 participants; 100 mg / day intake). To ensure proper evaluation, individuals who regularly take medication for chronic diseases, those taking health supplements that may affect clinical research, and those currently participating in other clinical research or trials, or who have participated in other clinical research or trials within the past three months, were excluded from the evaluation. The capsules were administered orally at 10:00 AM (between meals, on an empty stomach) with water or lukewarm water. Plasma estradiol levels were measured according to standard procedures by an external public institution. Figures 14a-c show the changes in plasma estradiol concentration (pg / ml) over 24 weeks. Figure 14a shows the changes for all subjects, Figure 14b shows the changes for male subjects, and Figure 14c shows the changes for female subjects. Figures 15a-c show the percentage change (%) in estradiol blood concentration up to 24 weeks after oral administration of nicotinamide mononucleotide to subjects over 24 weeks. Figure 15a shows the percentage change for all subjects, Figure 15b shows the percentage change for male subjects, and Figure 15c shows the percentage change for female subjects. Furthermore, Table 7 shows the values ​​of plasma estradiol concentration (pg / ml) before nicotinamide mononucleotide intake (week 0) and after nicotinamide mononucleotide intake (week 24). These values ​​represent the mean ± standard deviation.

[0077] [Table 7]

[0078] 2. Evaluation Results As can be seen from the results in Figures 14a-c and 15a-c, nicotinamide mononucleotide intake resulted in a high rate of increase in plasma estradiol concentration. These results confirm that oral administration of nicotinamide mononucleotide to middle-aged and elderly men and women promotes estradiol secretion, demonstrating its effectiveness in preventing aging. Furthermore, the subjects of the aforementioned evaluation showed no nonspecific symptoms such as abdominal pain, nausea, vomiting, headaches, or bowel irregularities even after 24 weeks of intake, confirming the safety of nicotinamide mononucleotide.

[0079] Example 8. Evaluation of the testosterone secretion-promoting effect of nicotinamide mononucleotide. To examine the changes in testosterone levels before and after nicotinamide mononucleotide intake, a study was conducted on healthy men and women aged 50-70. For Example 8, a capsule containing nicotinamide mononucleotide and starch (200 mg of nicotinamide mononucleotide in 4 capsules) (manufactured by Shinkowa Pharmaceutical Co., Ltd.) was used as a sample. Five healthy men and five healthy women aged 50-70 were administered a high dose of the aforementioned capsules, four capsules once daily for 24 weeks (total of 10 participants; 200 mg / day intake). To ensure proper evaluation, individuals who regularly take medication for chronic diseases, those taking health supplements that may affect clinical research, and those currently participating in other clinical research or trials, or who have participated in other clinical research or trials within the past three months, were excluded from the evaluation. The capsules were administered orally at 10:00 AM (between meals, on an empty stomach) with water or lukewarm water. Plasma testosterone levels were measured according to standard procedures by an external public institution. Figures 16a-c show the changes in plasma testosterone concentration (ng / ml) over 24 weeks. Figure 16a shows the changes for all subjects, Figure 16b shows the changes for male subjects, and Figure 16c shows the changes for female subjects. Figures 17a-c show the percentage change (%) in blood testosterone concentration up to 24 weeks after oral administration of nicotinamide mononucleotide to subjects over 24 weeks. Figure 17a shows the percentage change for all subjects, Figure 17b shows the percentage change for male subjects, and Figure 17c shows the percentage change for female subjects. Furthermore, Table 8 shows the plasma testosterone concentration (ng / ml) before nicotinamide mononucleotide intake (week 0) and after nicotinamide mononucleotide intake (week 24). These values ​​represent the mean ± standard deviation.

[0080] [Table 8]

[0081] 2. Evaluation Results As can be seen from the results shown in Figures 16a-c and 17a-c, nicotinamide mononucleotide intake resulted in a high rate of increase in plasma testosterone concentration. These results confirm that oral administration of nicotinamide mononucleotide to middle-aged and elderly men and women promotes testosterone secretion, demonstrating its effectiveness in preventing aging. Furthermore, the subjects of the aforementioned evaluation showed no nonspecific symptoms such as abdominal pain, nausea, vomiting, headaches, or bowel irregularities even after 24 weeks of intake, confirming the safety of nicotinamide mononucleotide.

[0082] Example 9. Evaluation of the prolactin secretion-promoting effect of nicotinamide mononucleotide. To examine the changes in prolactin levels before and after nicotinamide mononucleotide intake, a study was conducted on healthy men and women aged 50-70. For Example 9, a capsule containing nicotinamide mononucleotide and starch (100 mg of nicotinamide mononucleotide in 4 capsules) (manufactured by Shinkowa Pharmaceutical Co., Ltd.) was used as a sample. Five healthy men and five healthy women aged 50-70 were administered a high dose of the aforementioned capsules, four capsules once daily for 24 weeks (total of 10 participants; 100 mg / day intake). To ensure proper evaluation, individuals who regularly take medication for chronic diseases, those taking health supplements that may affect clinical research, and those currently participating in other clinical research or trials, or who have participated in other clinical research or trials within the past three months, were excluded from the evaluation. The capsules were administered orally at 10:00 AM (between meals, on an empty stomach) with water or lukewarm water. Plasma prolactin levels were measured according to standard procedures by an external public institution. Figures 18a-c show the changes in plasma prolactin concentration (ng / ml) over 24 weeks. Figure 18a shows the changes for all subjects, Figure 18b shows the changes for male subjects, and Figure 18c shows the changes for female subjects. Figures 19a-c show the percentage change (%) in prolactin blood concentration up to 24 weeks after oral administration of nicotinamide mononucleotide to subjects over 24 weeks. Figure 19a shows the percentage change for all subjects, Figure 19b shows the percentage change for male subjects, and Figure 19c shows the percentage change for female subjects. Furthermore, Table 9 shows the plasma prolactin concentration (ng / ml) before nicotinamide mononucleotide intake (week 0) and after nicotinamide mononucleotide intake (week 24). These values ​​represent the mean ± standard deviation.

[0083] [Table 9]

[0084] 2. Evaluation Results As can be seen from the results shown in Figures 18a-c and 19a-c, nicotinamide mononucleotide intake resulted in a high rate of increase in plasma prolactin concentration. These results confirm the prolactin secretion-promoting effect of oral administration of nicotinamide mononucleotide to middle-aged and elderly men and women, demonstrating its effectiveness in preventing aging. Furthermore, the subjects of the aforementioned evaluation showed no nonspecific symptoms such as abdominal pain, nausea, vomiting, headaches, or bowel irregularities even after 24 weeks of intake, confirming the safety of nicotinamide mononucleotide.

[0085] Example 10. Evaluation of the effect of nicotinamide mononucleotide on promoting adrenocorticotropic hormone secretion. To examine the changes in adrenocorticotropic hormone levels before and after nicotinamide mononucleotide ingestion, a study was conducted on healthy men and women aged 50-70. For Example 10, a capsule containing nicotinamide mononucleotide and starch (200 mg of nicotinamide mononucleotide in 4 capsules) (manufactured by Shinkowa Pharmaceutical Co., Ltd.) was used as a sample. Five healthy men and five healthy women aged 50-70 were administered a high dose of the aforementioned capsules, four capsules once daily for 24 weeks (total of 10 participants; 200 mg / day intake). To ensure proper evaluation, individuals who regularly take medication for chronic diseases, those taking health supplements that may affect clinical research, and those currently participating in other clinical research or trials, or who have participated in other clinical research or trials within the past three months, were excluded from the evaluation. The capsules were administered orally at 10:00 AM (between meals, on an empty stomach) with water or lukewarm water. Plasma levels of adrenocorticotropic hormone (ACTH) were measured by an external public institution according to standard procedures. Figures 20a-20c show the changes in plasma ADR concentration (pg / ml) over 24 weeks. Figure 20a shows the changes for all subjects, Figure 20b shows the changes for male subjects, and Figure 20c shows the changes for female subjects. Figures 21a-21c show the percentage change (%) in ADR blood concentration up to 24 weeks after oral administration of nicotinamide mononucleotide to subjects over 24 weeks. Figure 21a shows the percentage change for all subjects, Figure 21b shows the percentage change for male subjects, and Figure 21c shows the percentage change for female subjects. Furthermore, Table 10 shows the values ​​of plasma ADR concentration (pg / ml) before nicotinamide mononucleotide intake (week 0) and after nicotinamide mononucleotide intake (week 24). These values ​​represent the mean ± standard deviation.

[0086] [Table 10]

[0087] 2. Evaluation Results As can be seen from the results in Figures 20a-c and 21a-c, nicotinamide mononucleotide intake resulted in a high rate of increase in plasma adrenocorticotropic hormone (ACTH) concentration. These results confirm that oral administration of nicotinamide mononucleotide to middle-aged and elderly men and women promotes ACTH secretion, demonstrating its effectiveness in preventing aging. Furthermore, the subjects of the aforementioned evaluation showed no nonspecific symptoms such as abdominal pain, nausea, vomiting, headaches, or bowel irregularities even after 24 weeks of intake, confirming the safety of nicotinamide mononucleotide.

[0088] Example 11. Evaluation of the cortisol secretion-promoting effect of nicotinamide mononucleotide. To examine the changes in cortisol levels before and after nicotinamide mononucleotide ingestion, a study was conducted on healthy men and women aged 50-70. For Example 11, a capsule containing nicotinamide mononucleotide and starch (200 mg of nicotinamide mononucleotide in 4 capsules) (manufactured by Shinkowa Pharmaceutical Co., Ltd.) was used as a sample. Five healthy men and five healthy women aged 50-70 were administered a high dose of the aforementioned capsules, four capsules once daily for 24 weeks (total of 10 participants; 200 mg / day intake). To ensure proper evaluation, individuals who regularly take medication for chronic diseases, those taking health supplements that may affect clinical research, and those currently participating in other clinical research or trials, or who have participated in other clinical research or trials within the past three months, were excluded from the evaluation. The capsules were administered orally at 10:00 AM (between meals, on an empty stomach) with water or lukewarm water. Plasma cortisol levels were measured by an external public institution according to standard procedures. Figures 22a-22c show the changes in plasma cortisol concentration (μg / ml) over 24 weeks. Figure 22a shows the changes for all subjects, Figure 22b shows the changes for male subjects, and Figure 22c shows the changes for female subjects. Figures 23a-23c show the percentage change (%) in blood cortisol concentration up to 24 weeks after oral administration of nicotinamide mononucleotide to subjects over 24 weeks. Figure 23a shows the percentage change for all subjects, Figure 23b shows the percentage change for male subjects, and Figure 23c shows the percentage change for female subjects. Furthermore, Table 10 shows the plasma cortisol concentration (μg / dl) before nicotinamide mononucleotide intake (week 0) and after nicotinamide mononucleotide intake (week 24). These values ​​represent the mean ± standard deviation.

[0089] [Table 11]

[0090] 2. Evaluation Results As can be seen from the results in Figures 22a-c and 23a-c, nicotinamide mononucleotide intake resulted in a high rate of increase in plasma cortisol concentration. These results confirm that oral administration of nicotinamide mononucleotide to middle-aged and elderly men and women promotes cortisol secretion, demonstrating its effectiveness in preventing aging. Furthermore, the subjects of the aforementioned evaluation showed no nonspecific symptoms such as abdominal pain, nausea, vomiting, headaches, or bowel irregularities even after 24 weeks of intake, confirming the safety of nicotinamide mononucleotide.

[0091] Example 12. Evaluation of the calcitonin secretion-promoting effect of nicotinamide mononucleotide. To examine the changes in calcitonin levels before and after nicotinamide mononucleotide intake, a study was conducted on healthy men and women aged 50-70. For Example 12, a capsule containing nicotinamide mononucleotide and starch (200 mg of nicotinamide mononucleotide in 4 capsules) (manufactured by Shinkowa Pharmaceutical Co., Ltd.) was used as a sample. Five healthy men and five healthy women aged 50-70 were administered a high dose of the aforementioned capsules, four capsules once daily for 24 weeks (total of 10 participants; 200 mg / day intake). To ensure proper evaluation, individuals who regularly take medication for chronic diseases, those taking health supplements that may affect clinical research, and those currently participating in other clinical research or trials, or who have participated in other clinical research or trials within the past three months, were excluded from the evaluation. The capsules were administered orally at 10:00 AM (between meals, on an empty stomach) with water or lukewarm water. The amount of calcitonin in plasma was measured according to standard procedures by an external public institution. Figures 24a-24c show the changes in plasma calcitonin concentration (pg / ml) over 24 weeks. Figure 24a shows the changes for all subjects, Figure 24b shows the changes for male subjects, and Figure 24c shows the changes for female subjects. Figures 25a-25c show the percentage change (%) in blood calcitonin concentration up to 24 weeks after oral administration of nicotinamide mononucleotide to subjects over 24 weeks. Figure 25a shows the percentage change for all subjects, Figure 25b shows the percentage change for male subjects, and Figure 25c shows the percentage change for female subjects. Furthermore, Table 11 shows the values ​​of plasma calcitonin concentration (pg / ml) before nicotinamide mononucleotide intake (week 0) and after nicotinamide mononucleotide intake (week 24). These values ​​represent the mean ± standard deviation.

[0092] [Table 12]

[0093] 2. Evaluation Results As can be seen from the results shown in Figures 24a-c and 25a-c, nicotinamide mononucleotide intake resulted in a high rate of increase in plasma calcitonin concentration. These results confirm the calcitonin secretion-promoting effect of oral administration of nicotinamide mononucleotide to middle-aged and elderly men and women, demonstrating its effectiveness in preventing aging. Furthermore, the subjects of the aforementioned evaluation showed no nonspecific symptoms such as abdominal pain, nausea, vomiting, headaches, or bowel irregularities even after 24 weeks of intake, confirming the safety of nicotinamide mononucleotide.

[0094] Example 13. Evaluation of the effect of nicotinamide mononucleotide on promoting sirtuin 1 (Sirt1) secretion. To examine the changes in Sirt1 levels before and after nicotinamide mononucleotide intake, a study was conducted on healthy men and women aged 50-70. For Example 13, a capsule containing nicotinamide mononucleotide and starch (200 mg of nicotinamide mononucleotide in 4 capsules) (manufactured by Shinkowa Pharmaceutical Co., Ltd.) was used as a sample. Five healthy men and five healthy women aged 50-70 were administered a high dose of the aforementioned capsules, four capsules once daily for 24 weeks (total of 10 participants; 200 mg / day intake). To ensure proper evaluation, individuals who regularly take medication for chronic diseases, those taking health supplements that may affect clinical research, and those currently participating in other clinical research or trials, or who have participated in other clinical research or trials within the past three months, were excluded from the evaluation. The capsules were administered orally at 10:00 AM (between meals, on an empty stomach) with water or lukewarm water. The amount of Sirt1 in the blood was measured by an external public institution according to standard procedures. The mRNA expression level of the sirtuin gene Sirt1 was analyzed using real-time PCR from blood samples collected before nicotinamide mononucleotide ingestion (week 0) and after nicotinamide mononucleotide ingestion (week 24). For the analysis, the blood samples were purified to the cDNA level on the day of collection, stored at -80°C, and real-time PCR was performed on all samples at once. Expression levels were corrected using GAPDH as a reference gene. Table 12 shows the numerical values ​​of Sirt1 mRNA expression levels (GAPDH ratio). These values ​​represent the mean ± standard deviation.

[0095] [Table 13]

[0096] 2. Evaluation Results As shown in Table 12, nicotinamide mononucleotide intake increased the expression level of Sirt1 in the blood. These results confirm that oral administration of nicotinamide mononucleotide to middle-aged and elderly men and women promotes Sirt1 secretion, demonstrating its effectiveness in preventing aging. Furthermore, the subjects of the aforementioned evaluation showed no nonspecific symptoms such as abdominal pain, nausea, vomiting, headaches, or bowel irregularities even after 24 weeks of intake, confirming the safety of nicotinamide mononucleotide.

Claims

1. A hormone secretion enhancer containing nicotinamide mononucleotide as its active ingredient.

2. The hormone secretion promoter according to claim 1, wherein the hormone is growth hormone, ghrelin, adrenocorticotropic hormone, adrenocortical hormone, sex hormone, prolactin, parathyroid hormone, calcitonin, or melatonin.

3. The hormone secretion-promoting agent according to claim 1, administered orally to healthy human adults aged 50 to 70 years at a dose of 100 mg / day to 200 mg / day for 24 weeks.

4. A method for promoting hormone secretion by orally administering a hormone secretion-promoting agent according to any one of claims 1 to 4.

5. A method for promoting the secretion of a hormone according to claim 4, wherein the hormone is growth hormone, ghrelin, adrenocorticotropic hormone, adrenocortical hormone, sex hormone, prolactin, parathyroid hormone, calcitonin, or melatonin.

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