Longevity-enhancing composition

Abstract

To provide a means for promoting longevity that can be carried out relatively easily and can be used safely and continuously for a long period of time. The present invention provides a composition for promoting longevity, which contains, as an active ingredient, any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides containing any of these sugars. An example of a preferred active ingredient is galactosyl kojibiose.

Description

[Background technology]

[0001] The present invention relates to a composition for promoting longevity.

[0002] Living a long and healthy life is a goal that everyone aspires to. Calorie restriction is said to be one of the most common methods for extending lifespan. "Calorie restriction" here refers to "dietary restriction without causing malnutrition." However, it is difficult for people without sufficient nutritional knowledge to appropriately restrict dietary calories while still obtaining sufficient essential nutrients, and to continue this for an extended period of time.

[0003] Meanwhile, kojibiose and oligosaccharides containing it have several known uses. Patent Document 1 describes kojibiose as a novel, low-calorie food material that has caries-preventing effects and promotes the growth of bifidobacteria. Patent Document 2 describes an in vivo lipid-regulating agent containing one or more active ingredients selected from kojibiose, kojitriose, kojibiosyl glucoside, kojitetraose, and kojitriosyl glucoside. Patent Document 3 also describes an anti-inflammatory agent containing, as an active ingredient, a carbohydrate having a ketoaldohexose structure in its molecule, and lists 3-ketotrehalose, 3-ketokojibiose, 3-ketoisomaltose, 3-ketolactose, 3-ketomaltose, 3-ketosucrose, and 3-ketomaltitol as preferred examples of carbohydrates having a ketoaldohexose structure in its molecule. Patent Document 4 describes a composition for improving intestinal flora, which contains any one selected from the group consisting of kojibiose and oligosaccharides containing kojibiose as a constituent sugar. Patent Document 5 describes a method for producing galactosyl kojibiose, in which a composition containing galactosyl kojibiose is obtained by allowing a specific glucansucrase to act on a composition containing lactose and sucrose. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Publication No. 3-22957 [Patent Document 2] JP 2005-281188 A (Patent No. 4746281 A) [Patent Document 3] International Publication WO2017 / 018336 (Patent No. 6729913) [Patent Document 4] International Publication WO2024 / 043298 [Patent Document 5] International Publication WO2024 / 043297 Summary of the Invention [Problem to be solved by the invention]

[0005] It would be desirable to have a method that can promote longevity that is relatively easy to implement even for people without sufficient nutritional knowledge, and that can be used safely and continuously for a long period of time. [Means for solving the problem]

[0006] The present invention provides the following: [1] A composition for promoting longevity, comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars. [2] The composition described in 1, which contains galactosyl kojibiose. [3] The composition described in 1 or 2, which has the function of increasing the expression of the sirtuin 1 gene or a gene corresponding thereto. [4] The composition described in any one of 1 to 3, which has the function of increasing the expression of a superoxide dismutase gene or a gene corresponding thereto. [5] The composition according to any one of items 1 to 4, for activating a longevity regulating pathway. [6] The composition according to any one of items 1 to 5, for extending lifespan by 10% or more of the average lifespan. [7] A composition for increasing the expression of the sirtuin 1 gene or a gene corresponding thereto, comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars. [8] A composition for increasing the expression of a superoxide dismutase gene or a gene corresponding thereto, comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars.

[0007] The present invention also provides the following:

[11] A composition comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars, for use in a method for promoting longevity. Use of a composition comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars in the manufacture of a composition for promoting longevity. A method or non-therapeutic method for promoting longevity, comprising the step of administering to a subject a composition comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars. Use or non-therapeutic use of a composition comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars, for promoting longevity.

[12] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to 11, wherein the composition comprises galactosyl kojibiose.

[13] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to 11 or 12, wherein the composition has the function of increasing the expression of the Sirtuin 1 gene or a gene corresponding thereto.

[14] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to 11 or 12, wherein the composition has the function of increasing the expression of a superoxide dismutase gene or a gene corresponding thereto.

[15] The composition, use in manufacture, method or non-therapeutic method, or use or non-therapeutic use according to any one of claims 11 to 14, wherein the composition is for activating a longevity regulating pathway.

[16] A composition, use in manufacture, method or non-therapeutic method, or use or non-therapeutic use according to any one of claims 11 to 15, wherein the composition is intended to extend lifespan by 10% or more of the average lifespan.

[17] A composition comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars, for use in a method for increasing the expression of the sirtuin 1 gene or a gene corresponding thereto. Use of a composition comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars in the manufacture of a composition for increasing the expression of the sirtuin 1 gene or a gene corresponding thereto. A method or non-therapeutic method for increasing the expression of the sirtuin 1 gene or a gene corresponding thereto, comprising the step of administering to a subject a composition comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars. Use or non-therapeutic use of a composition comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars for increasing the expression of the sirtuin 1 gene or a gene corresponding thereto.

[17] A composition comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars, for use in a method for increasing the expression of a superoxide dismutase gene or a gene corresponding thereto. Use of a composition comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars in the manufacture of a composition for increasing the expression of a superoxide dismutase gene or a gene corresponding thereto. A method or non-therapeutic method for increasing the expression of a superoxide dismutase gene or a gene corresponding thereto, comprising the step of administering to a subject a composition comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars. Use or non-therapeutic use of a composition comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars for increasing the expression of a superoxide dismutase gene or a gene corresponding thereto. [Brief explanation of the drawings]

[0008] [Figure 1] Evaluation of the effect of intake concentration of kojibiose on survival rate. DETAILED DESCRIPTION OF THE INVENTION

[0009] (Embodiment 1) The present embodiment relates to a composition containing kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars as active ingredients.

[0010] [Active ingredient] In this embodiment, the active ingredient is any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides containing these as constituent sugars. "Oligosaccharides containing these as constituent sugars" refers to oligosaccharides containing kojibiose as a constituent sugar and oligosaccharides containing galactosyl kojibiose as a constituent sugar, and in the context of the present invention, they may also be referred to as "oligosaccharides containing kojibiose, etc." Oligosaccharides containing kojibiose, etc. as constituent sugars do not include kojibiose itself, nor do they include galactosyl kojibiose itself.

[0011] "Used as an active ingredient" means using an effective amount to exert the intended function, and using it in a way that clearly indicates that it contributes to the intended purpose. In functional food products, active ingredients are sometimes referred to as functional ingredients (ingredients that contribute to specific health purposes (excluding those related to reducing disease risk)).

[0012] In the present embodiment, unless otherwise specified, the term "any" is used to mean "at least one." "Any selected from kojibiose, galactosyl kojibiose, and oligosaccharides having kojibiose or any of them as their constituent sugars" includes cases where there is only kojibiose, only galactosyl kojibiose, only one type of oligosaccharide having kojibiose as its constituent sugar, only one type of oligosaccharide having galactosyl kojibiose as its constituent sugar, as well as cases where there is kojibiose and galactosyl kojibiose, a type of oligosaccharide having galactosyl kojibiose and two types of oligosaccharides having galactosyl kojibiose as their constituent sugar, etc.

[0013] The active ingredient is not particularly limited as long as it has the desired effect, and may be any of kojibiose, galactosyl kojibiose, and oligosaccharides containing these as constituent sugars, and may be one type or a combination of two or more types.

[0014] Examples of oligosaccharides containing kojibiose as a constituent sugar include the trisaccharides kojitriose, selaginose (kojibiosyl glucoside), centose, and kojibiosyl fructose, as well as the tetrasaccharides kojitetraose and kojitriosyl glucoside, which are formed by combining one molecule of a monosaccharide such as glucose with one of these trisaccharides.

[0015] In one embodiment, the active ingredient is either galactosyl kojibiose or an oligosaccharide having galactosyl kojibiose as a constituent sugar.

[0016] In this embodiment, unless otherwise specified, galactosyl kojibiose refers to kojibiose in which galactose is α- or β-linked to any of positions 1 to 8 of the following kojibiose. Theoretically, galactose can be linked to the OH at position 8 in four ways (α-α, α-β, β-α, and β-β), and to the OH at positions 2 to 7 in two ways, so 18 types of galactosyl kojibiose are expected. They are called 8α-α kojibiose, 8α-β kojibiose, 8β-α kojibiose, 8β-β kojibiose, 1α kojibiose, 2β kojibiose, 2α kojibiose, 2β kojibiose, 3α kojibiose, 3β kojibiose, 4α kojibiose, 4β kojibiose, 5α kojibiose, 5β kojibiose, 6α kojibiose, 6β kojibiose, 7α kojibiose, and 7β kojibiose, respectively.

[0017] [ka]

[0018] In one embodiment, the composition comprises any one of 18 types of galactosyl kojibiose, namely, 8α-α kojibiose, 8α-β kojibiose, 8β-α kojibiose, 8β-β kojibiose, 1α kojibiose, 2β kojibiose, 2α kojibiose, 2β kojibiose, 3α kojibiose, 3β kojibiose, 4α kojibiose, 4β kojibiose, 5α kojibiose, 5β kojibiose, 6α kojibiose, 6β kojibiose, 7α kojibiose, and 7β kojibiose, and may comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 of these.

[0019] In a preferred embodiment, the galactosyl kojibiose contained in the composition is α-D-glucopyranosyl-(1→2)-[β-D-galactopyranosyl-(1→4)-]D-glucopyranoside. This sugar can also be referred to as a type of glucosyllactose. It is also sometimes called 4'-galactosyl kojibiose.

[0020] Another study confirmed that kojibiose and galactosyl kojibiose have an excellent growth-promoting effect on bacteria of the genus Parabacteroides and Bifidobacterium (see Patent Document 4). Oligosaccharides containing kojibiose or the like as a constituent sugar can produce kojibiose or galactosyl kojibiose in the digestive tract of a subject after being ingested by the subject. Therefore, oligosaccharides containing kojibiose or the like as a constituent sugar can be fully expected to have the same effect as kojibiose or galactosyl kojibiose.

[0021] The origin and production method of kojibiose, galactosyl kojibiose, and oligosaccharides containing them as constituent sugars used as active ingredients are not particularly limited, and they may be produced by any method, such as fermentation, enzymatic methods, or organic synthesis. One preferred production method includes a step of treating a composition containing lactose and sucrose with glucansucrase, or lactic acid bacteria expressing glucansucrase, or a processed product thereof, to obtain a composition containing galactosyl kojibiose (Patent Document 5). In this embodiment, glucansucrase refers to an enzyme belonging to glycoside hydrolase (also known as glycosyl hydrolases) family 70 (GH70) (see (CAZy) databases, Cantarel et al., Nucleic Acids Res. 37:D233-238, 2009, and Patent Document 5).

[0022] The composition containing galactosyl kojibiose obtained by the above-mentioned production method can be used as is as a solution containing kojibiose, galactosyl kojibiose, and oligosaccharides containing these as constituent sugars, or after purification using an ion exchange resin or the like.

[0023] [Application] (Function / Action) In this embodiment, the active ingredient or a composition containing the active ingredient is used to promote longevity. Note that, although the use of this embodiment may be described below as the use of the active ingredient, this description also describes the use of the composition.

[0024] Longevity can be synonymous with longevity or longevity. Promoting longevity includes extending lifespan, helping to extend lifespan, improving health for longevity, activating longevity-regulating pathways, significantly enriching longevity-regulating pathway-multiple species in enrichment analysis, increasing the expression of sirtuin 1 (SIRT1) gene or its equivalent, and increasing the expression of superoxide dismutase (SOD) gene or its equivalent.

[0025] Whether an ingredient is effective in extending lifespan or helping to extend lifespan can be assessed as follows. Using appropriate experimental animals (e.g., wild-type control strain Drosophila (W1118)), two diets containing a relatively high amount of the target ingredient and two diets containing a relatively low amount of the target ingredient are prepared, and the lifespan of each group is measured. If necessary, a group is also provided with an appropriate control diet (which does not contain the target ingredient or contains standard ingredients instead). The lifespans of each group are compared, if necessary, by average, and if the lifespan of the experimental animals is extended in a concentration-dependent manner, the ingredient can be evaluated as being effective in extending lifespan or helping to extend lifespan.

[0026] In one aspect, the percentage of lifespan extension due to the active ingredient ((lifespan of the group taking the target ingredient - lifespan of the control group) / lifespan of the control group) is 5% or more, and may be 10% or more, 15% or more, 20% or more, 25% or more, or 30% or more.

[0027] In one embodiment, the active ingredient is used to activate a longevity regulating pathway.

[0028] Whether a compound is effective in activating or supporting the activation of the Longevity regulating pathway can be assessed by enrichment analysis. Enrichment analysis is an analysis that examines whether the proportion of genes with specific functions (GO terms) among genes whose expression levels change is statistically significantly higher in an experiment that examines changes in gene expression levels under different conditions (Hayashi Takeshi, Enrichment Analysis, Livestock Technology, June 2019 issue, pp. 48-49).

[0029] Enrichment analysis can be performed, for example, as follows: Differences in gene expression due to the presence or absence of a certain component are analyzed using DNA microarrays or other methods. The transcript list selected from the analysis is then imported into the Database for Annotation, Visualization and Integrated Discovery (DAVID) (National Institute of Allergy and Infectious Diseases (NIAID), NIH, https: / / david.ncifcrf.gov / home.jsp), and GO analysis and KEGG pathway analysis are performed using DAVID. KEGG pathway analysis is performed by having DAVID access the Kyoto Encyclopedia of Genes and Genomes (KEGG) database (www.genome.jp / kegg / ) and statistically extracting pathways that are highly correlated with the transcript list. A p-value for the correlation is calculated for each pathway, and statistically significant pathways can be identified based on the p-value, which may be adjusted, if necessary, using methods such as the Benjamini-Hochberg method (Benjamini, Y; Hochberg, Y (1995). "Controlling the false discovery rate: a practical and powerful approach to multiple testing". Journal of the Royal Statistical Society, Series B. 57 (1): 289-300.). As a result, if a test component shows a statistically significant increase in gene expression related to the Longevity-regulating pathway compared to when the component is not tested, the component can be evaluated as being effective in activating the Longevity-regulating pathway or in supporting the activation of the Longevity-regulating pathway.

[0030] Longevity-regulating pathways have been identified by KEGG (https: / / www.genome.jp / pathway / hsa04211). Human longevity-regulating pathways include the insulin signaling pathway, the p13K-Akt signaling pathway, the AMPK signaling pathway, the mTOR signaling pathway, and the FOXO signaling pathway.

[0031] The active ingredient of this embodiment has the function of increasing the expression of the Sirtuin 1 (SIRT1) gene or a gene equivalent thereto, and therefore, in one aspect, is used to increase the expression of the SIRT1 gene or a gene equivalent thereto. The "gene equivalent thereto" refers to a gene of another organism that corresponds to the SIRT1 gene of mammals, such as the dSir2 gene of flies or the Sir2.1 gene of worms.

[0032] The active ingredient of this embodiment has the function of increasing the expression of the superoxide dismutase (SOD) gene or a gene equivalent thereto, and therefore, in one aspect, is used to increase the expression of the SOD gene or a gene equivalent thereto. In this embodiment, the term "superoxide dismutase" refers to an enzyme (SOD molecular species) that dismutates superoxide (O2-) into oxygen (O2) and hydrogen peroxide (HO2), and unless otherwise specified, refers to any of mammalian SOD1, SOD2, and SOD3. The term "corresponding gene" refers to a gene of another organism that corresponds to the mammalian SOD1 gene, SOD2 gene, or SOD3 gene, such as the SOD gene of flies. In one aspect, the active ingredient has the function of increasing the expression of the mammalian SOD1 gene, SOD2 gene, or any of their corresponding genes, among SOD genes or genes equivalent thereto.

[0033] Without being bound by theory, the longevity-promoting or lifespan-extending effect of the composition of this embodiment may be due to an increase in the antioxidant function of SOD.

[0034] Gene expression refers to the production of mRNA from that gene. Whether a gene is expressed can be evaluated by whether mRNA is produced, and in some cases, by whether a protein translated from the mRNA is produced. The method for measuring mRNA production and protein production is not particularly limited, as long as production is confirmed by some method. Increased expression includes not only cases where expression is higher than normal (sometimes referred to as enhancement or promotion), but also cases where the decrease is suppressed in situations where expression is decreased.

[0035] Mammals have seven types of sirtuins, SIRT1 to SIRT7, and of these, SIRT1 is thought to be involved in controlling aging and lifespan. Enhanced expression of SIRT genes such as SIRT1 and / or enhanced 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); suppression of age-related weight gain; increase or enhancement of food intake, oxygen consumption, energy expenditure, or physical function; improvement of insulin resistance or serum lipid profile (independent of weight loss); improvement of ocular function (decrease or deterioration due to neurodegenerative diseases), bone mineral density, or bone marrow lymphocyte composition; and improvement of mitochondrial function in skeletal muscle (Mills et al., Cell Metab. 2016 December; 24(6):795-806); alleviation of obesity-related diseases and atherosclerosis (Li et al., Mol Cell. 2007 October; 28(1):91-106), and suppresses fatty liver, liver inflammation, and endoplasmic reticulum stress in the liver (Purushotham et al., Cell Metab. 2009 Apr; 9(4):327-38).

[0036] Mammals have three types of superoxide dismutases: cytosolic superoxide dismutase (SOD1), mitochondrial superoxide dismutase (SOD2), and extracellular superoxide dismutase (SOD3), which are known to play various roles (Antioxid Redox Signal. 2011, 15(6): 1583-1606. doi: 10.1089 / ars.2011.3999). For example, manganese superoxide dismutase (MnSOD, SOD2) levels are decreased in many diseases, including cancer, neurodegenerative diseases, and psoriasis, and MnSOD and its mimetics have potential applications as anti-inflammatory agents (Enzyme Research, 2011, Article ID 387176, doi:10.4061 / 2011 / 387176). Furthermore, MnSOD is beneficial in preventing ischemic stroke due to its antioxidant and oxidative stress-regulating properties, and it has been reported that MnSOD mimics reduced infarct volume and improved neurological function (CNS Neuroscience & Therapeutics 18 (2012) 811-818. doi.org / 10.1111 / j.1755-5949.2012.00380.x).Regarding the relationship with longevity and lifespan, it has been reported that curcumin extends the lifespan of Drosophila, and that this is related to the upregulation of Mn-SOD and CuZn-SOD genes (Age (Dordr). 2013; 35(4): 1133-1142. doi.org / 10.1007 / s11357-012-9438-2); overexpression of SOD-2 reduces mitochondrial superoxide in hippocampal neurons and extends the lifespan of mice (Neurobiology of Learning and Memory. 2007, 87(3): 372-384. doi.org / 10.1016 / j.nlm.2006.10.003); and in primates, it has been reported that the ratio of SOD activity to metabolic activity increases as the potential maximum lifespan increases (Proc. Natl. Acad. Sci. USA 1980, 77(5):2777-2781. doi.org / 10.1073 / pnas.77.5.2777).

[0037] (subject) The compositions of the present invention are suitable for ingestion by a subject for whom it is desirable or necessary to enhance longevity. In the present invention, "ingestion" is used to mean not only ingestion of food by a subject, but also administration of a pharmaceutical to a subject. "Ingestion" can be read as "administration," and vice versa.

[0038] In one embodiment, the subject is healthy (not having a medically diagnosed illness). The subject may be a human or a non-human animal.

[0039] The age of the subject is not particularly limited, and the subject may be, for example, a newborn (within 28 days of birth); an infant (less than 1 year of age); a toddler (1 to 6 years of age); a child (7 years or older, but less than 15 years of age); an adult (15 years or older); or a person 65 years or older. In a preferred embodiment, the subject is a relatively elderly person, for example, a person 60 years or older, a person 65 years or older, a person 70 years or older, or a person 75 years or older. It has been reported that the number of Fusobacterium bacteria in the intestinal tract increases with age (e.g., Odamaki et al. BMC Microbiology (2016) 16:90 DOI 10.1186 / s12866-016-0708-5).

[0040] [Composition] (Food composition, etc.) The composition of this embodiment can be a food composition or a pharmaceutical composition. Foods and pharmaceuticals include not only those for humans but also those for non-human animals, unless otherwise specified. Foods include general foods, functional foods, and nutritional compositions, as well as therapeutic foods (those that serve the purpose of treatment; prepared based on a menu created by a nutritionist or other professional prescribed by a doctor), dietary therapy foods, ingredient-modified foods, nursing care foods, and foods for medical support, unless otherwise specified. Foods include not only solid foods but also liquid foods, such as beverages, energy drinks, liquid foods, and soups, unless otherwise specified.

[0041] Functional foods refer to foods that can impart a specific functionality to the living body, and include a wide range of health foods, including foods for specified health uses (including conditional FOSHUs [foods for specified health uses]), foods with functional claims, health functional foods including foods with nutrient function claims, foods for special dietary uses, dietary supplements, health supplements, supplements (e.g., tablets, coated tablets, sugar-coated tablets, enteric-coated preparations such as enteric-coated preparations, enteric-coated preparation capsules (e.g., enteric-coated soft capsules, enteric-coated hard capsules, colon delivery capsules), and liquid preparations), dietary supplements, food supplements, medical foods (as defined by the U.S. Food and Drug Administration (FDA)), and beauty foods (e.g., diet foods). In this embodiment, "functional foods" also includes health foods to which a health claim based on the Codex Alimentarius (the Joint FAO / WHO Food Standards Commission) is applied. A food supplement is a concentrated form of nutrients or other substances, either alone or in combination, that supplements the normal diet and has a nutritional or physiological effect, and is labeled as a food supplement. A dietary supplement is a product (other than tobacco) intended to supplement the diet, contains one or more of the ingredients in question, and is labeled as a dietary supplement.

[0042] (Intake route, etc.) The composition of the present embodiment may be taken orally, parenterally, for example, via a tube (gastrostomy, enterostomy), or nasally, but is preferably taken orally.

[0043] The composition can be administered repeatedly to a subject, or can be administered continuously for a long period of time. The period is not particularly limited, but to ensure sufficient efficacy, it is recommended that the subject be administered the composition continuously for a relatively long period of time, for example, 3 days or more, 1 week or more, 2 weeks or more, 1 month or more, 3 months or more, 6 months or more, 1 year or more, 10 years or more, or even for the duration of their lifetime.

[0044] The compositions may be taken routinely, in advance, such as when at risk, or when the need arises. The compositions may be taken with a meal, before a meal, after a meal, or between meals.

[0045] (dose, content) The amount of intake of the composition of the present embodiment may be any amount that achieves the desired effect, and can be appropriately determined taking into consideration various factors such as the age, weight, and symptoms of the subject.

[0046] The content of the active ingredient in the composition can be adjusted appropriately depending on the form of the composition. For example, when the composition is a liquid such as a beverage, the content of the active ingredient per composition can be 0.5% or more, preferably 1% or more, more preferably 2% or more, and even more preferably 5% or more. Regardless of the lower limit, the upper limit of the active ingredient can be 20% or less, 18% or less, 16% or less, 13% or less, or 10% or less. In this embodiment, % means % by mass unless otherwise specified.

[0047] When the composition is in the form of a tablet or granular powder, the content of the active ingredient can be, for example, 10% or more, preferably 30% or more, more preferably 50% or more, and even more preferably 60% or more. When the composition is in the form of a tablet or granular powder, the upper limit of the content of the active ingredient can be 95% or less, 90% or less, or even 80% or less, regardless of the lower limit.

[0048] The daily intake of the composition can be 0.1 g or more, preferably 0.3 g or more, more preferably 0.6 g or more, and even more preferably 1 g or more, of the active ingredient (the total amount if multiple active ingredients are included). The upper limit of the active ingredient per day, regardless of the lower limit, can be 30 g or less, 25 g or less, 20 g or less, 18 g or less, 17 g or less, 16 g or less, or 15 g or less. When multiple active ingredients are included in the composition, the amount of active ingredient refers to the total amount of the active ingredients included.

[0049] The dosage may be once a day or multiple times a day, for example, 2 to 10 divided doses. The amount of active ingredient ingested per dose can be, for example, 0.01 g or more, preferably 0.3 g or more, more preferably 0.6 g or more, and even more preferably 1 g or more. The upper limit of the amount of active ingredient per dose, regardless of the lower limit, can be 50 g or less, 40 g or less, 30 g or less, 20 g or less, 18 g or less, 16 g or less, 14 g or less, 12 g or less, 10 g or less, or 5 g or less.

[0050] (Other ingredients, additives) In this embodiment, the composition may contain other active ingredients or nutritional ingredients that are acceptable as foods or pharmaceuticals. Examples of such ingredients include lipids (e.g., milk fat, vegetable oil, medium-chain fatty acid-containing oil), proteins (e.g., milk protein, milk protein concentrate (MPC), whey protein concentrate (WPC), whey protein isolate (WPI), α-lactalbumin (α-La), β-lactoglobulin (β-Lg), heat-denatured whey protein, and enzyme-treated whey protein), amino acids (e.g., lysine, arginine, glycine, alanine, glutamic acid, leucine, isoleucine, valine), and sugars other than water-soluble dietary fiber. Examples of suitable nutrients include glucose, sucrose, fructose, maltose, trehalose, erythritol, maltitol, palatinose, xylitol, and dextrin, electrolytes (e.g., sodium, potassium, calcium, and magnesium), vitamins (e.g., vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, biotin, folic acid, pantothenic acid, and nicotinic acids), minerals (e.g., copper, zinc, iron, cobalt, and manganese), antibiotics, and dietary fiber. The composition may also contain a component that activates SIRT1 or SOD. Examples of components that activate SIRT1 include NMN (Nature 403, 795-800 (2000)) and the fatty acid tryptamide (Scientific Reports 12(1), 12080 (2022)). An example of an ingredient that activates SOD is curcumin (see Age (Dordr). 2013; 35(4): 1133-1142, supra). In one embodiment, the composition may contain only an oligosaccharide having kojibiose or the like as a constituent sugar as an active ingredient, and may be free of other ingredients that activate SIRT1 or SOD.

[0051] In this embodiment, the composition may contain an ingredient effective as a prebiotic. Prebiotics are indigestible food ingredients that have a beneficial effect on the host and improve the host's health by selectively altering the growth and activity of specific bacteria in the large intestine. The composition may contain one or more types of prebiotics.

[0052] The prebiotics are not particularly limited as long as they do not interfere with the effects of the active ingredients contained in the composition. Examples of prebiotics include galactooligosaccharides, fructooligosaccharides, xylooligosaccharides, isomaltooligosaccharides, raffinose, lactulose, lactosucrose, soybean oligosaccharides, coffee oligosaccharides, insoluble dietary fiber, and gluconic acid.

[0053] The composition may further contain additives acceptable for food or pharmaceutical use, such as inert carriers (solid or liquid carriers), excipients, surfactants, binders, disintegrants, lubricants, solubilizers, suspending agents, coating agents, colorants, preservatives, buffers, pH adjusters, emulsifiers, stabilizers, sweeteners, antioxidants, flavors, acidulants, and natural products. More specifically, examples of the additives include water, other aqueous solvents, pharmaceutically acceptable organic solvents, collagen, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymers, sodium alginate, dextrin, water-soluble dextran, water-soluble dextrin, corn starch, sodium carboxymethyl starch, pectin, xanthan gum, gum arabic, casein, gelatin, agar, glycerin, propylene glycol, polyethylene glycol, petrolatum, paraffin, stearyl alcohol, stearic acid, magnesium stearate, precipitated calcium carbonate, talc, human serum albumin, mannitol, sorbitol, lactose, sucralose, lactose hydrate, candy powder, white sugar, stevia, aspartame, acesulfame potassium, citric acid, lactic acid, malic acid, tartaric acid, phosphoric acid, acetic acid, fruit juice, and vegetable juice.

[0054] (Dosage form / shape) The composition of this embodiment may be prepared in any form, such as a solid, liquid, mixture, suspension, powder, granules, paste, jelly, gel, or capsule. Furthermore, the food composition of this embodiment may be in any form, such as a dairy product, supplement, confectionery, beverage, drink, seasoning, processed food, prepared dish, or soup. More specifically, the composition of this embodiment may be in the form of a liquid diet, semi-liquid diet, jelly, gel, powder, infant formula, infant formula, liquid milk, powder or liquid milk for pregnant or nursing women, fermented milk, bar, mousse, chocolate, biscuit, ice cream, fermented milk, lactic acid bacteria drink, dairy drink, soft drink, tablet, cheese, bread, biscuit, cracker, pizza crust, food for the sick, nutritional food, frozen food, or processed food. It may also be in the form of a granule, powder, paste, or concentrated liquid for mixing with beverages or foods for consumption. The granules and powder may be in the form of cubes or sticks (single-serving packets). In this embodiment, modified powdered milk refers to a powder obtained by processing raw milk, cow's milk, special cow's milk, or raw buffalo milk, or a food made using these as an ingredient, or using these as a main ingredient, and adding nutrients necessary for infants, as defined in the Ministerial Ordinance on Milk, etc. In this embodiment, modified liquid milk refers to a liquid obtained by processing raw milk, cow's milk, special cow's milk, or raw buffalo milk, or a food made using these as an ingredient, or using these as a main ingredient, and adding nutrients necessary for infants, as defined in the Ministerial Ordinance on Milk, etc.

[0055] Formulated powdered milk or formulated liquid milk (these are sometimes collectively referred to as formula milks. In addition, formula milks are sometimes used as an example in explaining formula milks, but the explanation also applies to formula liquid milks.) can be for infants, follow-up (to supplement weaning food), low birth weight infants, children, adults, pregnant women, nursing women, the elderly, those with allergies, those with lactose intolerance, and those with inborn errors of metabolism. Preferred examples of formula milks are those for infants, follow-up, low birth weight infants, and children.

[0056] The pharmaceutical composition of the present embodiment can be in any dosage form suitable for oral ingestion, such as solid preparations such as tablets, granules, powders, pills, and capsules; liquid preparations such as solutions, suspensions, and syrups; gels; and aerosols.

[0057] (others) In the production of the composition of this embodiment, the stage of blending the active ingredient can be selected as appropriate. The stage of blending is not particularly limited as long as it does not significantly impair the properties of the active ingredient. For example, the active ingredient can be blended by mixing it with raw materials. Alternatively, the active ingredient can be added at the final stage of production to produce a composition containing the active ingredient.

[0058] The composition of this embodiment can display the intended use (application), and in one aspect, it displays a recommendation that the composition be taken by a specific subject. Examples of subjects to be displayed are as described above. In addition, in one aspect, the composition of this embodiment displays the function of the composition or active ingredient or a method of use based on that function. For example, it can display that the composition can promote longevity, can help promote longevity, can treat diseases or conditions that are improved by increased expression of the SIRT1 gene, etc. Note that a period such as "temporary" or "long-term" may be displayed at the beginning of each statement, as appropriate.

[0059] Representation can be explicit or implicit. Examples of explicit representation are direct inscriptions on tangible objects such as the product itself, packaging, containers, labels, tags, etc. Examples of implicit representation (which can also be called implicit) include advertising and promotional activities by place or means such as websites, stores, pamphlets, exhibitions, seminars such as media seminars, books, newspapers, magazines, television, radio, mail, email, and audio.

[0060] In one embodiment, the recommendation to consume the composition is displayed personally. Such a display can be made using a document (whether written or electronic) addressed to the subject, the subject's tablet device, smartphone, personal computer, or the subject's social media. Furthermore, such a display can be made together with the display of any test or analysis results for the subject. This can also be used for precision nutrition (individualized nutrition, which refers to proposing an appropriate diet (nutrition) tailored to an individual's constitution).

[0061] (Other embodiments) In other embodiments, the present invention provides a composition comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides containing these as constituent sugars for use in a method for promoting longevity; use of a composition comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides containing these as constituent sugars in the manufacture of a composition for promoting longevity; a method or non-therapeutic method for promoting longevity comprising the step of administering to a subject a composition comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides containing these as constituent sugars; and use or non-therapeutic use of a composition comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides containing these as constituent sugars for promoting longevity. The descriptions of the active ingredients, uses, compositions, etc. in the above embodiment 1 also apply to the other embodiments.

[0062] The present invention will be described in more detail below using examples. Note that the technical scope of the present invention is not limited to the above-mentioned embodiments, aspects, and examples. [Example]

[0063] [Lifespan extension effect of galactosyl kojibiose] Wild-type control strain Drosophila melanogaster (W1118) (Nagoya City University) was used. Adult flies were reared individually in glass tubes with an inner diameter of 3 mm and a length of 6.5 cm. They were fed standard medium (1% agar powder, 5% sucrose) containing 1% or 5% galactosyl kojibiose, and their lifespan was measured. Standard medium containing no galactosyl kojibiose was used as a control. Galactosyl kojibiose produced according to the method described in Patent Document 4 was used.

[0064] As shown in Figure 1, oral ingestion of galactosyl kojibiose extended the lifespan of Drosophila in a concentration-dependent manner.

[0065] Furthermore, the average lifespan after the start of intervention (n=32) was 18.6±4.8 days for the control, 22.3±3.2 days for 1% galactosyl kojibiose, and 24.0±4.9 days for 5% galactosyl kojibiose. Compared to the control, the 1% and 5% galactosyl kojibiose groups showed an average lifespan extension of approximately 20% and approximately 30%, respectively.

[0066] Next, the fruit flies were fed a standard diet containing 5% galactosyl kojibiose, and the genetic changes at 3 weeks of age (generally equivalent to middle-aged to adulthood in mammals) were compared with those of controls (raised on a standard diet).

[0067] Comprehensive gene expression analysis (Eukaryotic mRNA-Seq) RNA extracts (n = 3 per group) from 20 Drosophila heads were used as a single sample for RNASeq. Specifically, Drosophila frozen in liquid nitrogen were separated into heads and bodies by vortexing, and the heads were added to RNAiso Plus and homogenized. After centrifugation, RNA was extracted from the supernatant using phenol-chloroform. The RNA extracted sample was purified by ethanol precipitation and reconstituted in TE buffer to prepare the RNASeq sample. The RNASeq sample was sent to Novogene, where strand-specific library preparation, sequencing (Novaseq6000, Illumina), gene expression quantification using FeatureCounts, and enrichment analysis using GSEA were performed.

[0068] As a result, the "Longevity regulating pathway - multiple species" was significantly enriched in the group that ingested galactosyl kojibiose (p<0.01). When the genes whose expression increased in this pathway were confirmed, increased expression was observed in the dSir2 gene, which corresponds to the SIRT1 gene involved in lifespan extension in mammals, and the SOD gene, which corresponds to the SOD1 gene and SOD2 gene in humans, suggesting that galactosyl kojibiose may also have a lifespan extension effect in humans.

[0069] These results suggest that galactosyl kojibiose extends lifespan by at least 10%, more specifically at least 20%, and even more specifically at least 30% of the average lifespan. Furthermore, by increasing the expression of genes belonging to the longevity regulating pathway-multiple species, galactosyl kojibiose can activate the longevity regulating pathway. These findings suggest that galactosyl kojibiose promotes longevity. Furthermore, galactosyl kojibiose can increase the expression of the sirtuin 1 gene or a gene equivalent thereto, and of the genes encoding SOD molecular species represented by SOD1 and SOD2, or genes equivalent thereto.

[0070] Based on these results for galactosyl kojibiose, it can be said that kojibiose, oligosaccharides containing kojibiose as a constituent sugar, and oligosaccharides containing galactosyl kojibiose as a constituent sugar, which can be produced from galactosyl kojibiose in the digestive tract of a subject, can be expected to have the same effects as galactosyl kojibiose.

[0071] [Production of galactosyl kojibiose] (Preparation of enzyme solution) Galactosyl kojibiose can be produced as follows according to the method described in Patent Document 4.

[0072] Lactobacillus satsumensis JCM12392 is cultured overnight at 30°C using a commercially available MRS liquid medium, and then cooled to 10°C or below to terminate the culture.

[0073] The resulting culture medium is centrifuged, the supernatant is discarded, and the cells are collected. An equal volume of citrate phosphate buffer (pH 5.0) is added, and the cells are collected again to wash them. Half the volume of the original culture medium is added to the resulting cells, and the resulting suspension is used as the enzyme solution.

[0074] (enzyme reaction) 32 w / w% sucrose, 16 w / w% lactose, and 10 w / w% enzyme solution are mixed and allowed to react at 48°C for 18 hours under static conditions. The sugar composition after the reaction is 25-30% galactosyl kojibiose, 15-20% lactose, and 30-35% fructose per solid.

[0075] (purification) After the enzyme reaction mixture is passed through a carbon celite column, distilled water is passed through to remove non-adsorbed materials. Stepwise elution with aqueous ethanol solutions of varying concentrations yields a fraction consisting of a trisaccharide containing galactosyl kojibiose as the main component. [Industrial Applicability]

[0076] The present invention supports the maintenance and improvement of people's health through a longevity-promoting composition containing any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides containing these sugars. The present invention also provides a food composition and a method for producing food that support the maintenance and improvement of people's health. Furthermore, the present invention can improve the nutrition of various people, ensure healthy lives, and promote welfare.

Claims

1. A composition for promoting longevity, comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars.

2. The composition of claim 1 , comprising galactosyl kojibiose.

3. The composition according to claim 1, which has the function of increasing the expression of the sirtuin 1 gene or a gene corresponding thereto.

4. The composition according to claim 1, which has the function of increasing the expression of a superoxide dismutase gene or a gene corresponding thereto.

5. The composition of claim 1 for activating a longevity regulating pathway.

6. The composition of claim 1 for extending lifespan by 10% or more of the average lifespan.

7. A composition for increasing the expression of the sirtuin 1 gene or a gene corresponding thereto, comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars.

8. A composition for increasing the expression of a superoxide dismutase gene or a gene corresponding thereto, comprising any one selected from kojibiose, galactosyl kojibiose, and oligosaccharides having these as constituent sugars.

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