Anti-aging components

Abstract

To provide novel anti-aging compositions.SOLUTION: According to the present invention, provided is an anti-aging composition containing oils and fats containing β-position-long-chain saturated fatty acid as an active ingredient. According to the invention, also provided are a NMN production-promoting composition, a Nampt gene expression-enhancing composition, and a Sirt1 gene expression-enhancing composition, containing oils and fats containing β-position-long-chain saturated fatty acid, as an active ingredient. The oils and fats are preferably oils and fats containing β position-palmitic acid, and the compositions are preferably food compositions.SELECTED DRAWING: Figure 1

Description

Technical Field

[0005] , , ,

[0001] The present invention relates to a composition for anti-aging. The present invention also relates to a composition for promoting NMN production, a composition for enhancing Nampt gene expression, and a composition for enhancing Sirt1 gene expression.

Background Art

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

[0003] Recent studies have revealed that NMN decreases with aging and has effects on age-related diseases and anti-aging effects (Patent Document 1 and Non-Patent Document 1). Therefore, promoting NMN production in vivo is considered important for suppressing various functional declines that deteriorate with aging.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Non-Patent Documents

[0005]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0006] The present invention aims to provide novel anti-aging compositions. The present invention also aims to provide novel compositions for promoting NMN production, enhancing Nampt gene expression, and enhancing Sirt1 gene expression. [Means for solving the problem]

[0007] The inventors have now found that adding β-palmitic acid to human cultured cells significantly increases the expression levels of the Nampt gene and the Sirt1 (sirtuin 1) gene. The inventors have also found that adding β-palmitic acid to human cultured cells significantly increases the expression levels of the Nampt gene and the Sirt1 gene compared to the addition of β-myristic acid and β-stearic acid. The inventors have also found that in rats fed a test diet containing β-palmitic acid, the amount of NMN in the liver significantly increases in a manner dependent on the increasing proportion of β-palmitic acid in the test diet. The present invention is based on these findings.

[0008] The present invention provides the following inventions. [1] An anti-aging composition and an anti-aging agent comprising an oil containing a β-long-chain saturated fatty acid as an active ingredient. [2] A composition for promoting NMN production and an NMN production promoter comprising an oil containing a β-long-chain saturated fatty acid as an active ingredient. [3] A composition for enhancing Nampt gene expression and a Nampt gene expression enhancer comprising an oil containing a β-long-chain saturated fatty acid as an active ingredient. [4] A composition for enhancing Sirt1 gene expression and a Sirt1 gene expression enhancer comprising an oil containing a β-long-chain saturated fatty acid as an active ingredient. [5] A composition for maintaining, improving, treating or preventing a disease or condition that can be maintained, improved, treated or prevented by promoting NMN production, comprising an oil containing a β-long-chain saturated fatty acid as an active ingredient, and an agent for maintaining, improving, treating or preventing the said disease or condition. [6] A composition for maintaining, improving, treating or preventing a disease or condition that can be maintained, improved, treated or prevented by SIRT activation, comprising an oil containing a β-long-chain saturated fatty acid as an active ingredient, and an agent for maintaining, improving, treating or preventing the said disease or condition. [7] The composition and agent according to any one of [1] to [6] above, wherein the oil and fat is an oil and fat containing β-palmitic acid. [8] The composition and agent according to [7] above, wherein the ratio of palmitic acid at the β position to total palmitic acid in the oil and fat is 54% or more and less than 98%. [9] The composition and agent according to [5] above, wherein the oil and fat is an oil and fat containing β-palmitic acid, and in the oil and fat, the ratio of palmitic acid at the β position to total palmitic acid is 54% or more and less than 98%.

[10] The composition and agent according to [6] above, wherein the oil and fat is an oil and fat containing β-palmitic acid, and in the oil and fat, the ratio of palmitic acid at the β position to total palmitic acid is 54% or more and less than 98%.

[11] A food composition, which is any of the compositions and agents described in [1] to

[10] above.

[0009] In this specification, the compositions described in [1], [2], [3], [4], [5] and [6] above may be referred to as "the compositions of the present invention." Also in this specification, the agents described in [1], [2], [3], [4], [5] and [6] above may be referred to as "the agents of the present invention."

[0010] The active ingredients of the composition and agent of the present invention are oils and fats that have been used as food ingredients for many years. Therefore, the composition and agent of the present invention have the advantage of exhibiting anti-aging effects and being highly safe, as there is no concern about side effects even when continuously ingested over a long period of time. [Brief explanation of the drawing]

[0011] [Figure 1]Figure 1 shows the expression levels of the Nampt and Sirt1 genes in HepG2 cells after the addition of 2-palmitoylmonoglycerol (n=3) (Example 1). Measured values ​​are shown as mean ± standard deviation. Lowercase letters with different signs indicate statistical significance (Tukey-Kramer test). [Figure 2] Figure 2 shows the expression levels of the Nampt and Sirt1 genes in HepG2 cells after the addition of β-palmitic acid (2-palmitoylmonoglycerol) or β-oleic acid (2-oleoylmonoglycerol) (n=3) (Example 1). Measured values ​​are shown as mean ± standard deviation. ** indicates a statistically significant difference (p<0.01; Tukey-Kramer test). [Figure 3] Figure 3 shows the expression levels of the Nampt and Sirt1 genes in HepG2 cells after the addition of β-myristic acid (2-myristoylmonoglycerol), β-palmitic acid (2-palmitoylmonoglycerol), or β-stearic acid (2-stearoylmonoglycerol) (n=3) (Example 2). Measured values ​​are shown as mean ± standard deviation. * and ** indicate statistically significant differences (p<0.05 and p<0.01, respectively; Tukey-Kramer test). [Figure 4] Figure 4 shows the NMN concentrations in the liver of groups L, M, and H (n=4) (Example 3). Measured values ​​are shown as mean ± standard deviation. * indicates a statistically significant difference (p<0.05; Tukey-Kramer test). Detailed description of the invention

[0012] The compositions and agents of the present invention contain oils and fats containing β-long-chain saturated fatty acids as active ingredients. In the present invention, "β-long-chain saturated fatty acids" refers to substances in which long-chain saturated fatty acids are bonded to the β-position of a glyceride, and includes all compounds that are identical in chemical formula. That is, β-long-chain saturated fatty acids are acylglycerols in which long-chain saturated fatty acids are bonded to at least the β-position, and include acylglycerols (monoacylglycerols) in which long-chain saturated fatty acids are bonded to the β-position, acylglycerols (diacylglycerols) in which long-chain saturated fatty acids are bonded to the β-position and any fatty acid is bonded to either of the two α-positions, and acylglycerols (triacylglycerols) in which long-chain saturated fatty acids are bonded to the β-position and any fatty acid is bonded to each of the two α-positions. Furthermore, the β-long-chain saturated fatty acids may be pure or a mixture with other substances. For example, raw materials in which the presence of β-long-chain saturated fatty acids has been confirmed by a known measurement method may be used as is. Examples of the long-chain saturated fatty acids include saturated fatty acids having 12 to 24 carbon atoms, such as palmitic acid, lauric acid, myristic acid, stearic acid, arachidic acid, behenic acid, and lignoceric acid.

[0013] According to one embodiment of the present invention, a composition and agent containing a fat or oil containing β-palmitic acid is provided as an active ingredient. A typical raw material (mixture) rich in β-palmitic acid is lard, which can also be used in the composition and agent of the present invention. On the other hand, lard has a distinctive "animal odor," and it is known that to eliminate this, a raw material rich in β-palmitic acid can be obtained by chemically or enzymatically modifying a vegetable oil rich in palmitic acid (Japanese Patent Publication No. Hei 8-509620, Japanese Patent Publication No. Hei 8-509621, Japanese Patent Publication No. Hei 6-70786). Alternatively, a commercially available product of β-palmitic acid (for example, Betapol (Bunge Roders Krokran GmbH)) can be purchased and used in the composition and agent of the present invention by appropriately blending it with other raw materials.

[0014] In the oil and fat containing β-position-long chain saturated fatty acid which is the active ingredient of the present invention, the lower limit value of the ratio (mass ratio) of the long chain saturated fatty acid at the β-position of the glyceride to the total amount of fatty acids bound to the β-position (sn-2 position) can be set to 10% from the viewpoint of more effectively exerting the effects of the present invention, and from the viewpoint of stable production, the upper limit value can be set within a range not exceeding 90%.

[0015] In the oil and fat containing β-position-palmitic acid which is the active ingredient of the present invention, the lower limit value of the ratio (mass ratio) of palmitic acid at the β-position of the glyceride to the total amount of fatty acids bound to the β-position (sn-2 position) can be set to 10% from the viewpoint of more effectively exerting the effects of the present invention, preferably 50%, more preferably 74%. Also, from the viewpoint of stable production, the upper limit value of the above ratio can be set within a range not exceeding 90%, preferably 85%, more preferably 78%. These lower limit values and upper limit values can be arbitrarily combined respectively, and the range of the above ratio can be, for example, 50% or more and less than 90%, 70 - 85% or 74 - 78%.

[0016] In the oil and fat containing β-position-long chain saturated fatty acid which is the active ingredient of the present invention, further, the lower limit value of the ratio (binding ratio of the long chain saturated fatty acid to the β-position, mass ratio) of the long chain saturated fatty acid at the β-position of the glyceride to the total long chain saturated fatty acids can be set to 10% from the viewpoint of more effectively exerting the effects of the present invention, and from the viewpoint of stable production, the upper limit value can be set within a range not exceeding 98%.

[0017] In the oil and fat containing β-palmitic acid which is an active ingredient of the present invention, the lower limit value of the ratio of palmitic acid at the β-position of glyceride to total palmitic acid (the bonding ratio of palmitic acid to the β-position, mass ratio) can be 50% from the viewpoint of more effectively exhibiting the effects of the present invention, preferably 54%, more preferably 65%, still more preferably 67%, and particularly preferably 68%. Also, the upper limit value of the above ratio can be in the range not exceeding 98% from the viewpoint of stable production, preferably 75%, more preferably 74%, still more preferably 73%, and particularly preferably 72%. These lower limit values and upper limit values can be arbitrarily combined respectively, and the range of the above ratio can be, for example, 50% or more and less than 98%, 54 to 75%, 65 to 74%, 67 to 73% or 68 to 72%.

[0018] The composition and agent of the present invention can contain the oil and fat containing β-long-chain saturated fatty acid alone, or can also contain it mixed with other components. The content of the oil and fat containing β-long-chain saturated fatty acid in the composition and agent of the present invention can be, for example, 0.1 to 70% by mass, preferably 1 to 20% by mass. In the present invention, the agent of the present invention can be composed of the oil and fat containing β-long-chain saturated fatty acid, and the composition of the present invention can be made to contain the oil and fat containing β-long-chain saturated fatty acid.

[0019] The composition and agent of the present invention can contain the oil and fat containing β-palmitic acid alone, or can also contain it mixed with other components. The content of the oil and fat containing β-palmitic acid in the composition and agent of the present invention can be, for example, 0.1 to 20% by mass, preferably 1 to 9% by mass.

[0020] The compositions and agents of the present invention may contain other fats and oils in addition to fats and oils containing β-palmitic acid, such as fats and oils containing medium-chain fatty acids (e.g., medium-chain fatty acid glycerides) and general edible fats and oils (e.g., fats and oils mainly composed of long-chain fatty acids such as olive oil and soybean oil). The content of fats and oils other than those containing β-palmitic acid in the compositions and agents of the present invention can be, for example, 0 to 99% by mass, and preferably 10 to 40% by mass.

[0021] As shown in the examples below, it was confirmed that β-palmitic acid increases the expression level of the Nampt gene, and also increases the expression level of the Sirt1 gene. Furthermore, it was confirmed that the intake of β-palmitic acid increases the production of NMN downstream of the Nampt gene. Here, the production of NMN, a precursor of NAD+, increases, leading to increased NAD+ production, and the SIRT1 enzyme becomes active in the presence of its coenzyme, NAD+ (Jun Yoshino & Shinichiro Imai, Chemistry and Biology 2013; 51(3):147-153). Therefore, the intake of β-palmitic acid can increase the production of NMN and enhance SIRT1 enzyme activity by enhancing Sirt1 gene expression, thereby enhancing the NAD+-dependent protein deacetylation reaction, i.e., anti-aging effect. Thus, β-palmitic acid can be used to promote NMN production, enhance Nampt gene expression and Sirt1 gene expression, and can also be used for anti-aging purposes.

[0022] In this invention, "aging" generally refers to changes (decline) in physiological functions that occur after maturity. More specifically, these include: changes in the cardiovascular system such as coronary artery atherosclerosis and a decrease in maximum cardiac output during exercise; changes in the respiratory system such as a decrease in the number of alveoli and a decrease in lung elasticity; changes in the digestive system such as aspiration pneumonia due to a decrease in chewing and swallowing ability, constipation and bowel irregularities due to a decrease in gastrointestinal motility, and reflux esophagitis due to reflux of stomach contents into the esophagus; changes in the renal and urinary systems such as glomerular loss, decreased renal blood flow, and decreased filtration rate; changes in the skeletal system such as osteoporosis and fractures due to a decrease in bone mass and bone density, and arthritis due to a decrease in joint fluid and a decrease in synovial elasticity; and changes in audiovisual functions such as decreased vision and hearing. In the present invention, "anti-aging" includes maintaining the state before and after aging (i.e., keeping the state before and after aging at least in the same state, preferably suppressing or preventing changes (e.g., deterioration) in the state before and after aging), and improving the state before and after aging (i.e., making the state before and after aging better).

[0023] In addition to the above, it has been known that increasing the amount of NMN produced in vivo or enhancing the expression of Sirt genes such as Sirt1 and / or enhancing the activation of SIRT can alleviate cancer, cardiovascular disease, type II diabetes, obesity / impaired glucose tolerance, hypertension, and macular degeneration (Imai & Guarente, Trends Cell Biol. 2014 August; 24(8):464-471). Furthermore, it has been known that increasing the amount of NMN produced in vivo or enhancing the expression of Sirt genes such as Sirt1 and / or enhancing the activation of SIRT can suppress (age-related) weight gain; increase or improve food intake, oxygen consumption, energy consumption, or physical function; improve insulin resistance or serum lipid profile (independent of weight loss); improve eye function (decline or worsening due to neurodegenerative diseases), bone density, or bone marrow lymphocyte composition; and improve mitochondrial function in skeletal muscle (Non-Patent Literature 1). Furthermore, it is known that increasing the amount of NMN produced in vivo, or enhancing the expression of Sirt genes such as Sirt1 and / or enhancing the activation of SIRT, can alleviate obesity-related diseases and atherosclerosis (Li et al., Mol Cell. 2007 Oct; 28(1):91-106), and suppress fatty liver, hepatic inflammation, and hepatic endoplasmic reticulum stress (Purushotham et al., Cell Metab. 2009 Apr; 9(4):327-38). Here, the effect based on increased NMN production is known to be due to the action of NAD+, whose production is promoted by the increase in NMN, exerting its effect through the activation of SIRT, an NAD-dependent protein deacetylase. In addition, it is known that enhancing the expression of Sirt genes such as Sirt1 increases the amount of SIRT protein, increases the amount of SIRT activated by NAD+, and consequently enhances SIRT activation.Therefore, β-palmitic acid can be used to maintain, improve, treat or prevent diseases and conditions that can be maintained, improved, treated or preventable by promoting NMN production, as well as to maintain, improve, treat or prevent diseases and conditions that can be maintained, improved, treated or preventable by enhancing Sirt gene expression and / or SIRT activation. In this invention, SIRT refers to any of the seven proteins from SIRT1 to SIRT7 that constitute the Sirtuin family, and is not particularly limited, but is preferably SIRT1.

[0024] Diseases and conditions that can be maintained, improved, treated or prevented by promoting NMN production, as well as diseases and conditions that can be maintained, improved, treated or prevented by enhancing the expression of Sirt genes such as Sirt1 and / or activating SIRT, include aging (especially those with NAD+-dependent protein deacetylation); cancer; cardiovascular disease; type 2 diabetes; obesity and impaired glucose tolerance; hypertension; macular degeneration; weight gain (with age); dietary intake, oxygen consumption, energy consumption or physical function; insulin resistance or serum lipid profile (independent of weight loss); ocular function (especially decreased or worsened ocular function due to neurodegenerative diseases), bone density or bone marrow lymphocyte composition; mitochondrial function in skeletal muscle; obesity-related diseases; atherosclerosis; fatty liver; hepatic inflammation; and hepatic endoplasmic reticulum stress.

[0025] In this invention, "improvement" means making a certain state a better state. In this invention, "maintenance" means keeping a certain state at least in its original state, and includes suppressing or preventing a change in a certain state. "A certain state" includes a changed state and a normal state, and "normal state" includes the state before the change. Also, "change" is, for example, deterioration. In this invention, one aspect of "improvement" is the recovery of a deteriorated state. In this invention, one aspect of "maintenance" is the suppression or prevention of deterioration of a deteriorated state or a normal state.

[0026] The compositions and agents of the present invention can be provided in the form of pharmaceuticals and quasi-drugs (e.g., pharmaceutical compositions), foods (e.g., food compositions), animal feed (e.g., animal feed compositions), etc., and can be implemented according to the following description.

[0027] In the present invention, oils and fats containing β-long-chain saturated fatty acids can be administered orally to humans and non-human animals. Oral preparations include granules, powders, tablets (including sugar-coated tablets), pills, capsules, syrups, emulsions, and suspensions. These preparations can be formulated using pharmaceutically acceptable carriers by methods commonly practiced in the art. Pharmaceutically acceptable carriers include excipients, binders, diluents, additives, flavorings, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, and preservatives.

[0028] In the present invention, oils and fats containing β-long-chain saturated fatty acids can be administered to humans and non-human animals in ways other than oral administration, such as enteral or nasogastric tube administration, depending on the form of the composition and agent of the present invention. For example, by making the composition and agent of the present invention a viscous liquid composition containing oils and fats containing β-long-chain saturated fatty acids, or a semi-solid composition containing oils and fats containing β-long-chain saturated fatty acids, it can be ingested or administered to humans and non-human animals whose chewing and swallowing functions are impaired and who cannot take orally. By ingesting or administering the composition and agent of the present invention in ways other than oral ingestion, an anti-aging effect can be expected in the target, even if the chewing and swallowing functions of the target decline due to aging or other reasons.

[0029] In the present invention, oils and fats containing β-long-chain saturated fatty acids can be administered orally to humans and non-human animals. When oils and fats containing β-long-chain saturated fatty acids are administered orally, they may be in the form of isolated, purified, or crudely purified oils and fats, or in the form of food or food ingredients containing oils and fats containing β-long-chain saturated fatty acids.

[0030] In the present invention, when providing oils and fats containing β-long-chain saturated fatty acids as food, the oils and fats can be incorporated into the food, and such food is a food containing an effective amount of oils and fats containing β-long-chain saturated fatty acids. In the present invention, when providing oils and fats containing β-long-chain saturated fatty acids as food, food or raw materials that already contain the oils and fats can also be provided as food of the present invention, and such food is a food containing an effective amount of oils and fats containing β-long-chain saturated fatty acids. Here, "containing an effective amount" of oils and fats containing β-long-chain saturated fatty acids means an amount such that when the amount normally consumed in each food is ingested, the oils and fats containing β-long-chain saturated fatty acids are ingested within the range described later. Furthermore, "food" is used to include health foods, functional foods, health functional foods (e.g., Foods for Specified Health Uses, Nutrient Function Foods, Foods with Function Claims), foods for special dietary uses (e.g., foods for people with swallowing difficulties, infant formula, formula for pregnant and lactating women, foods for sick people), nutritional supplements, and foods for infants.

[0031] The form of "food" is not particularly limited; for example, it may be in liquid form such as beverages or liquid diets, or in paste, semi-liquid, or gel form, or in solid, bar, or powder form. When the composition and agent of the present invention are used in powder form, they can be manufactured by means of spray drying, freeze-drying, or other methods.

[0032] When the compositions and agents of the present invention are provided as foods containing oils and fats containing β-long-chain saturated fatty acids, they can be manufactured according to the usual methods for manufacturing foods, except for the addition of oils and fats containing β-long-chain saturated fatty acids. That is, the foods of the present invention can be prepared by adding oils and fats containing β-long-chain saturated fatty acids, regardless of whether they are in liquid, solid, or powder form, to various foods (for example, milk, soft drinks, fermented milk, yogurt, chocolate, gummies, cheese, bread, biscuits, cookies, crackers, pizza crusts, jelly, ice cream, high-energy supplements, high-energy pastes, powdered milk, liquid foods, foods for special dietary uses, foods for the sick, complete nutrition foods, nutritional supplements, frozen foods, processed foods, and other commercially available foods) or their raw materials. Alternatively, the subject can ingest oils and fats containing β-long-chain saturated fatty acids in various forms (liquid, solid, powder, paste, etc.) by adding them to water, food, or meals. In particular, in the present invention, by incorporating an effective amount of oil containing β-long-chain saturated fatty acids into liquid food, it is possible to create a food that also possesses anti-aging functions. Such a food is advantageous because it can be ingested or administered to sick or elderly people whose chewing and swallowing functions have deteriorated.

[0033] When the compositions and agents of the present invention are provided in the form of foods or raw materials (especially processed raw materials) that already contain oils and fats containing β-long-chain saturated fatty acids, examples of such foods and raw materials include edible oils and fats such as lard and vegetable oils.

[0034] The compositions and agents of the present invention are suitable for consumption by middle-aged and elderly individuals who require anti-aging effects.

[0035] In the present invention, for example, oils and fats containing β-long-chain saturated fatty acids can be combined with other raw materials to provide compositions or supplements for anti-aging purposes.

[0036] The daily intake or dosage of the compositions and agents of the present invention as pharmaceuticals or foods is not particularly limited, as it varies depending on the patient's condition, age, symptoms, weight, intended use, etc. For intake and administration aimed at anti-aging, the daily intake or dosage (in terms of solid content) of oils containing β-long-chain saturated fatty acids (especially β-palmitic acid) for adults is not particularly limited, but the lower limit is, for example, 0.01 g, preferably 0.1 g. The upper limit is, for example, 65 g or 60 g, preferably 5 g or 1 g. These lower and upper limits can be combined arbitrarily. The number and frequency of intake or administration can be appropriately determined according to the desired degree of anti-aging effect. The intake and dosage, as well as the intake and administration intervals, can be determined by the patient's attending physician, pharmacist, registered dietitian, nutritionist, care worker, care manager, helper, staff at care facilities, family members, or the patient themselves.

[0037] The compositions and agents of the present invention are not limited to being used in combination with other orally ingestible compositions or agents. For example, the anti-aging effect can be further enhanced by using them in combination with materials or compositions that are expected to have anti-aging effects, such as antioxidants.

[0038] The compositions and agents of the present invention can be provided in a daily intake amount effective for anti-aging effects. In this case, the compositions and agents of the present invention may be packaged to allow for the intake of a daily effective intake of oils and fats containing β-long-chain saturated fatty acids, and the packaging may be a single package or multiple packages, as long as the daily effective intake can be consumed. When provided in package form, it is desirable that the package or a document containing such information be provided so that the daily effective intake can be consumed. Furthermore, when providing a daily effective intake in multiple packages, the multiple packages of the daily effective intake may be provided as a set for convenience of consumption.

[0039] The packaging form for providing the composition and agent of the present invention is not particularly limited as long as it specifies a certain amount, and examples include packaging paper, bags, soft bags, paper containers, cans, bottles, capsules, and other containers capable of holding them.

[0040] To better exert their effects, the compositions and agents of the present invention are preferably administered or ingested continuously for at least one week, with the administration and ingestion period being preferably two weeks or more (e.g., 2 to 14 weeks), and more preferably three weeks or more (e.g., 3 to 21 weeks). Here, "continuously" means administering or ingesting at least once per week (e.g., 1 to 7 times). When the compositions and agents of the present invention are provided in packaged form, a set containing an effective intake amount for a certain period (e.g., one week) for continuous intake may be provided.

[0041] The food of the present invention may be labeled as having anti-aging properties. In this case, in order to make the labeling easy for consumers to understand, the food of the present invention may be labeled with some or all of the following labels, for example. • For those concerned about aging • Makes it easier for people with impaired liver function due to aging or alcohol consumption to burn fat (improves and enhances liver function). • Improves fat utilization in overweight individuals (those prone to gaining weight) and reduces body fat (making it less likely for fat to accumulate in the liver even after eating). • Improves motor function in individuals with energy deficiency (improves frailty) • For those who want to increase their appetite

[0042] According to another aspect of the present invention, there is a method for anti-aging, a method for promoting NMN production, a method for enhancing Nampt gene expression, or a method for enhancing Sirt1 gene expression, comprising administering or ingesting an oil or fat containing an effective amount of β-long-chain saturated fatty acids or a composition comprising the same to a subject in need. The present invention also provides a method for maintaining, improving, treating or preventing a disease or condition that can be maintained, improved, treated or prevented by promoting NMN production, comprising administering or ingesting an oil or fat containing an effective amount of β-long-chain saturated fatty acids or a composition comprising the same to a subject in need. The present invention also provides a method for maintaining, improving, treating or preventing a disease or condition that can be maintained, improved, treated or prevented by SIRT activation, comprising administering or ingesting an oil or fat containing an effective amount of β-long-chain saturated fatty acids or a composition comprising the same to a subject in need. The methods of the present invention can be carried out in accordance with the description relating to the compositions and agents of the present invention.

[0043] According to another aspect of the present invention, the use of oils and fats containing β-long-chain saturated fatty acids or compositions comprising them is also provided for the production of anti-aging agents, NMN production promoters, Nampt gene expression enhancers or Sirt1 gene expression enhancers, or in anti-aging methods, NMN production promoters, Nampt gene expression enhancers or Sirt1 gene expression enhancers. According to the present invention, the use of oils and fats containing β-long-chain saturated fatty acids or compositions comprising them is also provided for the production of agents for maintaining, improving, treating or preventing diseases or conditions that can be maintained, improved, treated or prevented by promoting NMN production, or in methods for maintaining, improving, treating or preventing diseases or conditions that can be maintained, improved, treated or prevented by promoting NMN production. The present invention also provides for the use of oils and fats containing β-long-chain saturated fatty acids or compositions comprising them, as agents for maintaining, improving, treating or preventing diseases or conditions that can be maintained, improved, treated or prevented by SIRT activation, or as agents for maintaining, improving, treating or preventing diseases or conditions that can be maintained, improved, treated or prevented by SIRT activation, or in methods for maintaining, improving, treating or preventing diseases or conditions that can be maintained, improved, treated or prevented by SIRT activation. The use of the present invention can be carried out in accordance with the descriptions of the compositions and agents of the present invention and the methods of the present invention.

[0044] According to yet another aspect of the present invention, oils and fats containing β-long-chain saturated fatty acids or compositions comprising them are provided for use in anti-aging, NMN production promotion, Nampt gene expression enhancement, or Sirt1 gene expression enhancement. The present invention also provides oils and fats containing β-long-chain saturated fatty acids or compositions comprising them for use in maintaining, improving, treating, or preventing diseases or conditions that can be maintained, improved, treated, or prevented by promoting NMN production. The present invention also provides oils and fats containing β-long-chain saturated fatty acids or compositions comprising them for use in maintaining, improving, treating, or preventing diseases or conditions that can be maintained, improved, treated, or prevented by SIRT activation. These inventions can be carried out in accordance with the descriptions of the compositions and agents of the present invention and the methods of the present invention.

[0045] The methods and uses of the present invention may be used in mammals, including humans, and are intended for both therapeutic and non-therapeutic use. In this specification, “non-therapeutic” means that it does not include any act of surgery, treatment or diagnosis of a human being (i.e., medical practice on a human being), and more specifically, it means that it does not include any method by which a physician or a person under the direction of a physician performs surgery, treatment or diagnosis on a human being. [Examples]

[0046] The present invention will be described more specifically based on the following examples, but the present invention is not limited to these examples.

[0047] Example 1: Effect of β-palmitic acid on the expression levels of the Nampt and Sirt1 genes (1) In Example 1, the effect of β-palmitic acid on the expression levels of the Nampt and Sirt1 genes was confirmed using cultured cells.

[0048] (1) Test method Human liver-derived HepG2 cell lines were seeded at a density of 100,000 cells / 0.5 mL / well, cultured for 48 hours, and confirmed to have reached 80% confluence before being used in experiments 1 and 2.

[0049] <Test 1> The aforementioned 80% confluent cells were exposed to 100 μM, 250 μM, 500 μM, and 1000 μM β-palmitic acid (2-palmitoyl monoglycerol) (all at a final BSA concentration of 1%) for 3 hours. RNA was then extracted from the cells, and the expression levels of the Nampt and Sirt1 genes were measured by real-time PCR using the primers shown in Tables 1-3. The expression levels of each gene were corrected for the expression level of the Actb gene using the ΔΔCt method to calculate the expression ratio.

[0050] [Table 1]

[0051] [Table 2]

[0052] [Table 3]

[0053] <Exam 2> The 80% confluent cells were exposed to 500 μM β-palmitic acid (2-palmitoyl monoglycerol) or β-oleic acid (2-oleoyl monoglycerol) (both with a final ethanol concentration of 0.1% and a final BSA concentration of 1%) for 4 hours. As a control, the 80% confluent cells were also exposed to 0.1% ethanol and 1% BSA (control (EtOH+)) or 1% BSA (control (EtOH-)) for 4 hours. Subsequently, the expression levels of the Nampt gene and Sirt1 gene were measured by real-time PCR in the same manner as in Experiment 1.

[0054] (2) Results The results are shown in Figures 1 and 2. Figure 1 shows that the expression levels of the Nampt and Sirt1 genes tended to increase in a concentration-dependent manner with the addition of 2-palmitoyl monoglycerol. Figure 2 shows that the expression levels of the Nampt and Sirt1 genes significantly increased with the addition of 2-palmitoyl monoglycerol compared to the control, while the addition of 2-oleoyl monoglycerol did not change the expression levels of the Nampt and Sirt1 genes. No effect on gene expression levels was observed with a final ethanol concentration of 0.1%.

[0055] Example 2: Effect of β-palmitic acid on the expression levels of the Nampt and Sirt1 genes (2) In Example 2, the effects of β-palmitic acid, β-myristic acid, or β-stearic acid on the expression levels of the Nampt and Sirt1 genes were examined using cultured cells.

[0056] (1) Test method Human liver-derived HepG2 cell lines were seeded at a density of 100,000 cells / 0.5 mL / well, cultured for 48 hours, and confirmed to have reached 80% confluence before being used in the study.

[0057] The 80% confluent cells were exposed to 500 μM β-myristic acid (2-myristoyl monoglycerol), β-palmitic acid (2-palmitoyl monoglycerol), or β-stearic acid (2-stearoyl monoglycerol) (all with a final ethanol concentration of 0.1% and a final BSA concentration of 1%) for 4 hours. As a control, the 80% confluent cells were also exposed to 0.1% ethanol and a final BSA concentration of 1% (control (EtOH+)) for 4 hours. Subsequently, the expression levels of the Nampt gene and Sirt1 gene were measured by real-time PCR in the same manner as in Test 1 of Example 1 above. However, in Example 2, the expression levels of each gene were calculated based on calibration curves created with each primer, and the expression ratio was determined by correcting with the expression level of the Actb gene.

[0058] (2) Results The results are shown in Figure 3. From the results in Figure 3, it was confirmed that the expression levels of the Nampt gene and Sirt1 gene were significantly increased by the addition of 2-palmitoylmonoglycerol compared to the control, 2-myristoylmonoglycerol, and 2-stearoylmonoglycerol. These results indicate that among β-long-chain saturated fatty acids with 14 to 18 carbon atoms, β-palmitic acid has superior anti-aging effects.

[0059] Example 3: Effect of palmitic acid β-bond ratio on metabolites in rat liver In Example 3, the effect of differences in the β-bonding ratio of palmitic acid in the test diet on liver metabolites was examined in rats. This study was conducted with the approval of Meiji Co., Ltd.'s Animal Ethics Review Board ("Meiji Animal Ethics Review Board No. 2016_3871_0064").

[0060] (1) Preparation of test food Two types of test oils shown in Table 4 (low-β-palmitic acid content oil: L oil and high-β-palmitic acid content oil: H oil) were mixed to prepare three types of test foods shown in Table 5 (low-β-palmitic acid content food: L food, moderate-β-palmitic acid content food: M food, high-β-palmitic acid content food: H food).

[0061] [Table 4]

[0062] In Table 4, "Palmitic Acid Content Ratio" represents the ratio (mass ratio) of palmitic acid bound to triglycerides to the total amount of fatty acids in the test oil. "β-Position Bonding Ratio of Palmitic Acid" represents the ratio (mass ratio) of palmitic acid bound to the β-position (sn-2 position) of triglycerides to the total amount of palmitic acid.

[0063] [Table 5]

[0064] (2) Test method Six-week-old male rats (SLC Japan) were reared for one week to acclimate them, then divided into three test groups (four rats per group). Each group was designated as a low-β-palmitic acid diet group (L group), a medium-β-palmitic acid diet group (M group), and a high-β-palmitic acid diet group (H group), and each group was given one of the test diets prepared in (1) above for one week. During the test period, the rats were allowed free feeding and drinking. On the last day of rearing, total blood was collected from the abdominal aorta under isoflurane anesthesia, and the liver was removed. Next, 1,500 μL of 50% acetonitrile aqueous solution (v / v) (internal standard substance concentration: 10 μM) was added to the liver samples (four samples from each test group), and the samples were crushed using a lithotripter under cooling (1,500 rpm, 120 seconds x 2 times). After tissue crushing, centrifugation (2,300 × g, 4℃, 5 min) was performed. After centrifugation, the upper 400 μL was transferred to an ultrafiltration tube (Ultrafree MC PLHCC, HMT, centrifugal filter unit 5 kDa). This was centrifuged (9,100 × g, 4°C, 120 min) and ultrafiltration was performed. The filtrate was allowed to dry, and then dissolved again in 50 μL of Milli-Q water to prepare the sample.

[0065] The above samples were subjected to capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF / MS: Agilient CE-TOFMS system (Agilient Technologies), Capillary: Fused silica capillary id Liver metabolites were comprehensively analyzed using cation and anion modes with a 50 μm × 80 cm (microscope) sensor. Specifically, the analysis targeted substances registered in the HMT metabolite library and the Known-Unknown peak library. For 275 annotated peaks (154 cations, 121 anions), the mean and standard deviation of the peak area were calculated for each substance, and Welch's t-test was performed on the obtained analytical results. In addition, quantitative values ​​were calculated for the peaks of 81 substances (47 cations, 34 anions) detected among the target metabolites. Furthermore, comparative analysis of the obtained analytical results was performed on groups L, M, and H. Specifically, for each substance, the peak area ratio of group M to group L and group H to group L were determined, and statistical significance was determined by the p-value. Statistical significance was determined using Welch's t-test.

[0066] (3) Results There were 35 metabolites that showed significant differences between the L and H groups, and among them, NMN was found to have the largest area ratio between the H and L groups. Furthermore, as shown in Figure 4, it was confirmed that the amount of NMN was significantly higher in the H group compared to the L or M group, and that the amount of NMN was lowest in the L group and highest in the H group, in the order of L group, M group, and H group. From these results, it was confirmed that the amount of NMN in the liver increases in a manner dependent on an increase in the ratio of palmitic acid bound to the β position of triglycerides in the test diet.

[0067] Example 4: Examples of formulations in food compositions for the elderly In Example 4, a food composition (beverage) for the elderly was prepared according to the formulation (per 100 ml) shown in Table 6. In addition to beverages, jelly drinks, powdered beverages, solid formulations, powder formulations, etc., can also be manufactured by known methods.

[0068] [Table 6]

Claims

1. An anti-aging composition comprising an oil containing a β-long-chain saturated fatty acid as an active ingredient, wherein the β-long-chain saturated fatty acid is β-palmitic acid.

2. The composition according to claim 1, for use in promoting NMN production, enhancing Nampt gene expression, or enhancing Sirt1 gene expression.

3. The composition is a composition for use in promoting NMN production, The composition according to claim 2, which is a composition for maintaining, improving, treating or preventing a disease or condition that can be maintained, improved, treated or prevented by promoting NMN production.

4. The composition is a composition for use in enhancing Sirt1 gene expression, The composition according to claim 2, which is a composition for maintaining, improving, treating or preventing a disease or condition that can be maintained, improved, treated or prevented by SIRT activation.

5. The composition according to claim 1, wherein the ratio of palmitic acid at the β-position to total palmitic acid in the oil and fat is 54% or more and less than 98%.

6. The composition according to claim 2, wherein the ratio of palmitic acid at the β-position to total palmitic acid in the oil is 54% or more and less than 98%.

7. The composition according to claim 3, wherein the ratio of palmitic acid at the β position to total palmitic acid in the oil and fat is 54% or more and less than 98%.

8. The composition according to claim 4, wherein the ratio of palmitic acid at the β-position to total palmitic acid in the oil is 54% or more and less than 98%.

9. A food composition, according to any one of claims 1 to 8.

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