JP7591364B2 - Composition for extending healthy lifespan - Google Patents

Description

NPMD NITE BP-02621 NPMD NITE BP-01633

The present invention relates to a composition for extending healthy lifespan.

In recent years, the relationship between intestinal bacteria and health has attracted attention, and research is being conducted around the world. "Probiotics," a term known for improving the intestinal environment, generally refers to live microorganisms that have a beneficial effect on humans by improving the balance of intestinal flora.
Furthermore, there are also "prebiotics" that are assimilated by such probiotics, which generally refers to substances that are not broken down or absorbed in the upper digestive tract, but serve as a selective nutrient source for beneficial bacteria that live symbiotically in the large intestine, promoting their proliferation, improving and maintaining a healthy balance in the composition of intestinal flora in the large intestine, and helping to promote and maintain human health.

The main probiotics known are Bifidobacterium bacteria (also known as bifidobacteria) and lactic acid bacteria.
Bifidobacterium bacteria have been reported to have various beneficial effects on hosts such as humans, such as prevention of diarrhea, reduction of harmful bacteria and toxic compounds, immunomodulation, and anticarcinogenic activity (Non-Patent Documents 1 to 3).
It has been reported that some lactic acid bacteria exhibit preventive and defensive effects against various infectious diseases by activating the host's cellular immunity and enhancing the secretion of immune substances from the mucous membranes of the intestinal tract and respiratory tract (Non-Patent Documents 4 to 7). In addition, strains that are excellent in these effects have been found (Patent Documents 1 and 2).

International Publication No. 2012/133827 International Publication No. 2015/004949

S. Fukuda et al., Nature, 2011, 469, 543-547. S. Fanning et al., PNAS, 2012, 109 (6), 2108-2113. Sivan A. et al., Science. 2015, 350 (6264), 1084-1089. Delcenserie, V. et al., Curr. Issues Mol. Biol. (2008) 10: 37-54. Hori, T. et al., Clin. Diagn. Lab. Immunol. (2002) 9: 105-108. Takeda, K. et al., Clin. Exp. Immunol. (2006) 146: 109-115. Ogawa, T., Clin. Exp. Immunol. (2006) 143: 103-109.

There are many unknowns regarding the functionality of probiotics, and research is still ongoing into the changes in functionality when multiple types of probiotics are combined.
In this situation, an objective of the present invention is to discover and provide new health functionality of probiotics.

As a result of intensive research aimed at solving the above problems, the inventors discovered that a composition containing a combination of Bifidobacterium bacteria and Lacticaseibacillus bacteria has the effect of extending healthy lifespan, thereby completing the present invention.

That is, the present invention relates to a composition for extending healthy lifespan, which contains bacteria of the genus Bifidobacterium and bacteria of the genus Lacticaseibacillus.
The Bifidobacterium bacterium of the present invention is preferably Bifidobacterium longum. Furthermore, the Bifidobacterium longum of the present invention is preferably Bifidobacterium longum NITE BP-026
The number is 21.
The Lacticaseibacillus bacterium of the present invention is preferably Lacticaseibacillus paracasei. Furthermore, the Lacticaseibacillus paracasei of the present invention is Lacticaseibacillus paracasei NITE BP-01633
It is.
The Bifidobacterium bacteria and/or Lacticaseibacillus bacteria in the present invention may be live bacteria and/or killed bacteria.
Preferably, the composition of the present invention further contains a prebiotic.
The prebiotic is preferably lactulose.
In the present invention, the extension of healthy life expectancy is preferably achieved by preventing and/or ameliorating frailty.
The composition of the present invention is preferably a food or drink.

According to the present invention, by preventing and improving frailty, it is possible to extend healthy life expectancy. Therefore, this can contribute to leading a social life while maintaining a healthy state of mind and body in an aging society.

Next, the present invention will be described in detail. However, the present invention is not limited to the following embodiments, and can be freely modified within the scope of the present invention.

The composition of the present invention contains bacteria of the genus Bifidobacterium and bacteria of the genus Lacticaseibacillus. In the present invention, the composition may contain one or more types of bacteria of the genus Bifidobacterium and one or more types of bacteria of the genus Lacticaseibacillus, in combination.

Examples of the Bifidobacterium bacteria include, but are not limited to, Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium infantis,
Infantis), Bifidobacterium bifidum, Bifidobacterium adolescentis, Bifidobacterium catenulatum, Bifidobacterium pseudocatenulatum, Bifidobacterium animalis, Bifidobacterium lactis, and Bifidobacterium pseudolongum.

More specifically, Bifidobacterium longum BB536 can be mentioned as Bifidobacterium longum. Bifidobacterium longum BB536 is available from the National Institute of Technology and Evaluation, Patent Microorganisms Depositary (NPMD) (〒292-0818, Japan).
This bacterium was deposited internationally under the Budapest Treaty at the National Institute of Health, Laboratories, Chiba Prefecture, Japan, under the accession number NITE BP-02621 on January 26, 2018. The same bacterium, Bifidobacterium longum subsp. longum ATCC BAA-999 (number: ATCC BAA-999), is A
American Type Culture Collection (ATCC; United States, 2
10801 University Boulevard, Manassas, Virginia 0110
01 University Boulevard, Manassas, VA 2011
0, United States of America) to ATCC BAA-9
99 (see, for example, JP 2012-223134 A).

More specifically, Bifidobacterium breve M-16V can be mentioned. Bifidobacterium breve M-16V was internationally deposited under the Budapest Treaty with the NPMD on January 26, 2018 under the accession number NITE BP-02622. Commercially available products, such as "Bifidobacterium breve M-16V" manufactured by Morinaga Milk Industry Co., Ltd., may be used.
More specifically, Bifidobacterium breve MCC 1274 can be mentioned as well. Bifidobacterium breve MCC 1274 has been internationally deposited on August 25, 2009 at the National Institute of Advanced Industrial Science and Technology (currently National Institute of Technology and Evaluation Patent Organism Depositary (IPOD) (Room 120, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, 292-0818) under the deposit number FERM BP-11175 based on the Budapest Treaty.

More specifically, Bifidobacterium infantis can be exemplified by Bifidobacterium longum subsp. infantis M-63. Bifidobacterium longum subsp. infantis M-63 is
This is synonymous with Bifidobacterium infantis M-63, which was internationally deposited under the Budapest Treaty with the NPMD on January 26, 2002 under the accession number NITE BP-02623.

Among these Bifidobacterium bacteria, Bifidobacterium longum is more preferable, and among them, Bifidobacterium longum BB536 (Accession No.: NITE
BP-02621) is particularly preferred.

The genus Lacticaseibacillus was previously classified as a member of the Lactobacillus genus, but was reclassified to the genus Lacticaseibacillus in the International Journal of Systematic and Evolutionary Microbiology (IJSEM) in 2020 in accordance with the rules (ICNP) of the International Committee on Prokaryotic Nomenclature (ICSP).
The newly classified genus Lacticaseibacillus includes Lacticaseibacillus casei, Lacticaseibacillus paracasei, and Lacticaseibacillus rhamnosus.

Lactobacillus casei, more specifically Lactobacillus casei YI
T9029 (FERM BP-1366), Lactobacillus casei ATCC393, etc.
Lactobacillus casei YIT9029 has been internationally deposited in the IPOD under the accession number FERM BP-01366 based on the Budapest Treaty as a bacterium belonging to the genus Lactobacillus, which is a former classification.
Lactobacillus casei ATCC393 is available from the American Type Culture Collection (ATCC; address: 12301 Parklawn Drive, Rockville, Maryland 20852, United States of America).

More specifically, examples of Lactobacillus paracasei include Lactobacillus paracasei MCC1849, Lactobacillus paracasei MCC1375, Lactobacillus paracasei KW3110, and Lactobacillus paracasei WON0604.
Lactobacillus paracasei MCC1849 was deposited at the NPMD on June 6, 2013 under the accession number of NITE P-01633 as a bacterium of the genus Lactobacillus, which is a former classification, and was transferred to an international deposit under the Budapest Treaty on January 31, 2014, and was assigned the accession number of NITE BP-01633.
Lactobacillus paracasei MCC1375 was internationally deposited under the Budapest Treaty on November 5, 2010 at the National Institute of Advanced Industrial Science and Technology (currently IPOD) as a bacterium of the genus Lactobacillus, which is a former classification, under the accession number FERM BP-11313.
Lactobacillus paracasei KW3110 has been internationally deposited at IPOD under the accession number FERM BP-08634 under the Budapest Treaty, while L. casei L1
4 strain is also available from the Japan Dairy Technology Association.
Lactobacillus paracasei WON0604 has been internationally deposited under the Budapest Treaty at IPOD under the accession number FERM BP-11468.

More specifically, examples of Lacticaceibacillus rhamnosus include Lactobacillus rhamnosus LCS742, Lactobacillus rhamnosus ATCC53103, and the like.
Lactobacillus rhamnosus LCS742 is a product of Morinaga Milk Industry Co., Ltd.
rhamnosus LCS-742 (see, for example, JP-A-2009-522280).
Lactobacillus rhamnosus ATCC 53103 is available from the American Type Culture Collection.
Among these bacteria belonging to the genus Lacticaceobacillus, Lacticaceobacillus paracasei is more preferable, and among them, Lacticaceobacillus paracasei MCC1849 (Accession No.: NIT
EBP-01633) is particularly preferred.

The above-mentioned strains of the genus Bifidobacterium and Lacticaseibacillus are not limited to the strains deposited or registered under the name of the bacteria at a designated institution (hereinafter, for convenience of explanation, also referred to as "deposited strains"), but also include strains that are substantially equivalent thereto (also referred to as "derived strains" or "derived strains"). In other words, they are not limited to the strains deposited at the depository institution under the above accession numbers, but also include strains that are substantially equivalent thereto. Regarding bacteria, "strains that are substantially equivalent to the above-mentioned deposited strain" refers to bacteria that belong to the same species as the above-mentioned deposited strain, and further have a similarity in genome sequence (average nucleotide identity value) with the above-mentioned deposited strain of preferably 99.0% or more,
More preferably, it refers to a strain having 99.5% or more identity, and even more preferably 100%, and preferably having the same bacteriological properties as the deposited strain. For bacteria, a strain substantially equivalent to the deposited strain may be, for example, a derivative strain having the deposited strain as a parent strain. Examples of the derivative strain include a strain bred from the deposited strain and a strain naturally occurring from the deposited strain. Examples of the breeding method include modification by genetic engineering techniques and modification by mutation treatment. Examples of the mutation treatment include irradiation with X-rays, irradiation with ultraviolet rays, and treatment with mutagens such as N-methyl-N'-nitro-N-nitrosoguanidine, ethyl methanesulfonate, and methyl methanesulfonate. Examples of the strain naturally occurring from the deposited strain include a strain naturally occurring during use of the deposited strain. Examples of such strains include mutant strains naturally occurring by culturing (e.g., subculturing) the deposited strain. The derivative strain may be constructed by one type of modification, or by two or more types of modifications.

The Bifidobacterium genus bacteria and Lacticaseibacillus genus bacteria contained in the composition of the present invention may be commercially available products, or may be obtained by appropriate production, or may be obtained by culturing the above-mentioned bacteria.
The culture method is not particularly limited as long as the bacteria of the genus Bifidobacterium or Lacticaseibacillus can grow. As the culture method, for example, a method usually used for culturing bacteria of the genus Bifidobacterium or Lacticaseibacillus can be used as is or with appropriate modification. The culture temperature may be, for example, 25 to 50°C, and preferably 35 to 42°C. The culture can be preferably performed under anaerobic conditions, for example, while aerating with anaerobic gas such as carbon dioxide gas. The culture can also be performed under microaerobic conditions such as liquid static culture. The culture can be performed, for example, until the bacteria grow to a desired extent.

The medium used for the culture is not particularly limited as long as the Bifidobacterium bacteria or Lacticaceabacillus bacteria can grow. For example, the medium may be a medium that is generally used for the culture of the bacteria, either as is or after appropriate modification. That is, as the carbon source, sugars such as galactose, glucose, fructose, mannose, cellobiose, maltose, lactose, sucrose, trehalose, starch, starch hydrolysate, and blackstrap molasses can be used depending on the assimilation. As the nitrogen source, for example, ammonium salts such as ammonia, ammonium sulfate, ammonium chloride, and ammonium nitrate, and nitrates can be used. In addition, as the inorganic salt, for example, sodium chloride, potassium chloride, potassium phosphate, magnesium sulfate, calcium chloride, calcium nitrate, manganese chloride, and ferrous sulfate can be used. In addition, organic components such as peptone, soybean flour, defatted soybean meal, meat extract, and yeast extract may be used. In addition, specific examples of media commonly used for culturing the above bacteria include Reinforced Clostridial medium, de Man, Rogosa, and Sharpe medium (MRS medium), modified MRS medium (mMRS medium), TOS propionate medium (TOSP medium), TOS propionate mupirocin medium (TOSP Mup medium), and GAM (Gifu Anaerobic
Examples of the medium include Yeast Extract-casein Hydrolysate Acid (YCFA) medium and Yeast Extract-casein Hydrolysate Acid (YCFA) medium.

The form of the Bifidobacterium and Lacticaseibacillus bacteria contained in the composition of the present invention may be any of bacterial cells, a bacterial culture, and a treated bacterial product, each independently.
The bacterial cells may be, for example, live bacterial cells, dead bacterial cells (including injured bacterial cells), or a mixture of live bacterial cells and dead bacterial cells. The Bifidobacterium bacteria and the Lacticaseibacillus bacteria may be independently selected from live bacterial cells, dead bacterial cells, and a mixture thereof. In a preferred embodiment, the Bifidobacterium bacteria are contained in the composition of the present invention as live bacterial cells, and the Lacticaseibacillus bacteria are contained in the composition of the present invention as dead bacterial cells.
As the bacterial culture, for example, the culture obtained by culturing may be used as it is, the culture may be diluted or concentrated, or the bacterial cells recovered from the culture may be used. In addition, the culture may be a culture supernatant or a culture fraction. When the culture supernatant is used, for example, the supernatant of the culture solution obtained by culturing in GAM medium at 37° C. for 16 hours can be preferably used.
The processed bacterial material may be a product obtained by subjecting bacterial cells or cultures to crushing, heating, freeze-drying, or spray-drying, as well as a diluted product, dried product, or fraction thereof.

The content of each of the Bifidobacterium and Lacticaseibacillus bacteria in the composition of the present invention is not particularly limited, but for example, the amount of the bacteria is preferably 1.0×10 ⁴ cfu or more per 1 g of the composition, and more preferably 1.0×10 ⁷ cfu or more per 1 g of the composition.
In the present specification, the cfu refers to a value obtained when the bacteria is cultured at 38° C. in a solid medium containing 10% by mass of reconstituted skim milk powder. In addition, when the bacteria are killed, the cfu can be replaced with the unit of cells.
When a culture supernatant is used as the bacterial culture, the content is preferably 0.1 to 100% by mass, more preferably 1 to 90% by mass, and even more preferably 10 to 80% by mass of the entire composition.
Furthermore, the content ratio of the Bifidobacterium genus bacteria and the Lacticaseibacillus genus bacteria in the composition of the present invention is not particularly limited, but is preferably 0.1:99.9 to 99.9:0.1, more preferably 1:99 to 99:1, even more preferably 10:90 to 90:10, and even more preferably 30:70 to 70:30, in terms of the bacterial cell mass expressed in cfu, for example.
These contents may be within the range generally used when distributed as oral compositions.

The composition of the present invention preferably further contains a prebiotic. Prebiotics mainly refer to substances that have the effect of promoting the proliferation of probiotics and inhibiting the decrease thereof in the intestine. In the present invention, those that have the effect of promoting the proliferation and/or inhibiting the decrease of Bifidobacterium bacteria are particularly preferred.
Preferred examples of prebiotics include oligosaccharides (lactulose, galactooligosaccharides, fructooligosaccharides, xylooligosaccharides, isomaltooligosaccharides, raffinose, lactosucrose, soybean oligosaccharides, coffee oligosaccharides, human milk oligosaccharides, etc.), monosaccharides (galactose, mannose, etc.), and dietary fibers (inulin, alginic acid, etc.). Of these, oligosaccharides are more preferred, and lactulose is even more preferred.

The amount of prebiotics contained in the composition of the present invention is not particularly limited, but can be, for example, 0.1 to 90% by mass of the entire composition. Alternatively, it can be 1 to 900 mg per 1 g of the composition.

The composition of the present invention can extend healthy lifespan. "Healthy longevity" is an index proposed by the World Health Organization (WHO) and refers to the period obtained by subtracting the period of nursing care such as bedriddenness or dementia from the average lifespan. Extending healthy lifespan does not mean simply living longer, but rather extending the period of time in which one lives in a mentally and physically healthy state. It can also be said to shorten the period of nursing care, or to shorten the overall period by delaying the onset or progression of bedriddenness or dementia.

The healthy life expectancy extension effect exerted by the composition of the present invention is preferably due to the prevention and/or amelioration of frailty. Here, the prevention of frailty includes prevention of frailty and delay of the onset of frailty, and the amelioration of frailty includes suppression of frailty and delay of the progression of frailty.
"Frailty" refers to a state of frailty that occurs when the physiological reserve capacity declines in old age, increasing vulnerability to stress and falling between a healthy state and a state of impaired daily living functions or a state requiring nursing care (see statement by the Japan Geriatrics Society https://jpn-geriat-soc.or.jp/info/topics/pdf/20140513_01_01.pdf). This state of frailty is a concept that includes not only physical problems such as loss of agility due to decreased muscle strength and increased susceptibility to falls, but also mental and psychological problems such as cognitive impairment and depression, and social problems such as living alone and financial hardship. In general, frailty is not considered irreversible, but rather reversible, and can be restored to a healthy state with appropriate intervention.

There are no unified criteria for diagnosing frailty, but the Cardiovascular Health Study criteria (CHS criteria) based on a phenotype model and the Frailty Index based on a deficit accumulation model are known as major methods, and improvement in these scores can be used to determine improvement in frailty. In addition, the FRAIL scale and Edmonton Frail Scale (
Improvement in frailty may be determined using the Examination of Patients' Frailty Scale (EFS), the Tilburg Frailty Indicator (TFI), the Key Checklist (KCL), the Brief Frailty Index, and the like.

The Japanese version of the CHS criteria (J-CHS) uses five evaluation criteria: weight loss, muscle weakness, fatigue, decreased walking speed, and decreased physical activity.
As shown in the examples below, the ingestion of the composition of the present invention has an appetite improving effect, and therefore an improvement in the evaluation of "weight loss" is expected. In addition, the ingestion of the composition of the present invention has a sleep improving effect and a fatigue recovery effect, and therefore an improvement in the evaluation of "fatigue". In addition, the ingestion of the composition of the present invention has a muscle mass increasing effect, and therefore an improvement in the evaluation of "muscular weakness", "decreased walking speed", or "decreased physical activity" is expected.
Therefore, the composition of the present invention can prevent and/or improve frailty from physical and/or mental/psychological aspects, thereby extending healthy lifespan.
It is presumed that such effects are obtained additively or synergistically by combining bacteria of the genus Bifidobacterium and bacteria of the genus Lacticaseibacillus.

Another aspect of the present invention is the use of Bifidobacterium and Lacticaseibacillus bacteria in the manufacture of a composition for extending healthy lifespan.
Another aspect of the present invention is the use of Bifidobacterium and Lacticaseibacillus bacteria in extending healthy lifespan.
Another aspect of the present invention is a Bifidobacterium or Lacticaseibacillus bacterium for use in extending healthy lifespan.
Another aspect of the present invention is a method for extending healthy lifespan, comprising administering to a subject bacteria of the genus Bifidobacterium and bacteria of the genus Lacticaseibacillus.

The subject to which the composition of the present invention is administered (recipient) and the subject to which the composition is ingested (recipient) are animals, but are usually humans. In addition, the subject may be an adult, a child, an infant, a newborn, etc., but is usually an adult, and preferably an elderly person (65 years or older). In addition, there are no particular limitations on the gender.

In this specification, "administering Bifidobacterium bacteria and Lacticaseibacillus bacteria to an animal" may be synonymous with "allowing an animal to ingest Bifidobacterium bacteria and Lacticaseibacillus bacteria." Ingestion is usually voluntary (free intake), but may also be forced (forced intake). That is, the administration step may specifically be, for example, a step of blending Bifidobacterium bacteria and Lacticaseibacillus bacteria into food, drink, or feed and supplying them to the subject, thereby allowing the subject to ingest them freely.

The timing of intake (administration) of the composition of the present invention is not particularly limited and can be appropriately selected depending on the condition of the subject to be taken (administered).

The intake (administration) amount of the composition of the present invention is appropriately selected depending on the age, sex, condition, other conditions, etc. of the subject to be ingested (administered).
The intake (administration) amount of the composition of the present invention is, for example, preferably 1×10 ⁷ to 1×10 ¹² cfu/day, more preferably 1×10 ⁸ to 1×10 ¹¹ cfu/day, and even more preferably 1×10 ⁹ to 1×10 ¹¹ cfu/day for adults, as the intake (administration) amount of the Bifidobacterium bacteria of the present invention. Also, the intake (administration) amount of the Lacticaceibacillus bacteria is, for example, preferably 1×10 ⁷ to 1×10 ¹² cfu/day, more preferably 1×10 ⁸ to 1×10 ¹¹ cfu/day, and even more preferably 1×10 ⁹ to 1×10 ¹¹ cfu/day for adults.
Alternatively, the intake (administration) amount of the culture supernatant of Bifidobacterium genus bacteria is, for example, preferably in the range of 0.5 to 5 g/day for adults, more preferably in the range of 1 to 4 g/day, and even more preferably in the range of 2 to 3 g/day. The intake (administration) amount of the culture supernatant of Lacticaseibacillus genus bacteria is, for example, preferably in the range of 0.5 to 5 g/day for adults, more preferably in the range of 1 to 4 g/day, and even more preferably in the range of 2 to 3 g/day.
Regardless of the amount or period of ingestion (administration), the composition of the present invention can be ingested (administered) once a day or in multiple divided doses.

The intake (administration) period of the composition of the present invention is not particularly limited. In addition, there is no particular upper limit to the intake (administration) period, and continuous, long-term intake (administration) is possible.

The composition of the present invention may be taken (administered) either orally or parenterally, with oral administration being preferred. Examples of parenteral intake (administration) include transdermal, intravenous, rectal, and inhalation.

When the composition of the present invention is intended to be orally ingested (administered), it is preferably in the form of a food or beverage.

There are no particular limitations on the form or properties of the food or beverage product, so long as it does not impair the effects of the present invention and can be orally ingested (administered), and other than containing Bifidobacterium genus bacteria and Lacticaseibacillus genus bacteria, the food or beverage product can be produced by ordinary methods using raw materials normally used for food or beverage products.

Food and drink products include, regardless of their form, liquid, paste, gel-like solid, powder, etc., for example, nutritional supplements, tablet confectioneries; liquid foods (nutritional foods for tube feeding); wheat flour products such as bread, macaroni, spaghetti, noodles, cake mix, fried chicken flour, breadcrumbs, etc.; instant foods such as instant noodles, cup noodles, retort/prepared foods, canned foods, microwave foods, instant soups/stews, instant miso soup/cleansing liquids, canned soups, freeze-dried foods, and other instant foods; Agricultural processed products such as canned agricultural products, canned fruit, jams and marmalades, pickles, boiled beans, dried agricultural goods, and cereals (processed grain products); marine processed products such as canned seafood, fish ham and sausages, seafood paste products, seafood delicacies, and tsukudani (food stew); livestock processed products such as canned livestock products and pastes, livestock ham and sausages; dairy products such as processed milk, milk drinks, yogurt, lactic acid bacteria drinks, cheese, ice cream, modified milk powder, cream, and other dairy products; butter, margarines, and vegetable oils Fats and oils; basic seasonings such as soy sauce, miso, sauces, processed tomato seasonings, mirin, vinegars; complex seasonings and foods such as cooking mixes, curry bases, sauces, dressings, noodle soups, spices, and other complex seasonings; frozen foods such as ingredient frozen foods, semi-cooked frozen foods, and cooked frozen foods; caramel, candy, chewing gum, chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japanese sweets, rice snacks, bean snacks, desserts These include confectioneries such as candy, jellies, and other sweets; carbonated drinks, natural fruit juice, fruit juice drinks, soft drinks with fruit juice, fruit pulp drinks, fruit drinks with fruit particles, vegetable drinks, soy milk, soy milk drinks, coffee drinks, tea drinks, powdered drinks, concentrated drinks, sports drinks, nutritional drinks, alcoholic drinks, and other beverages; other commercially available foods such as baby food, furikake, and ochazuke nori; infant formula; enteral nutrition; functional foods (foods for specified health uses, foods with nutritional functions), etc.

In addition, one aspect of the food and drink may be feed, such as pet food, livestock feed, and fish feed.
The form of the feed is not particularly limited, and in addition to Bifidobacterium bacteria and Lacticaseibacillus bacteria, it may contain, for example, grains such as corn, wheat, barley, rye, milo, etc.; vegetable oil cakes such as soybean oil cake, rapeseed oil cake, palm oil cake, linseed oil cake, etc.; bran such as wheat bran, wheat bran, rice bran, defatted rice bran, etc.; manufacturing residues such as corn gluten meal and corn jam meal; animal feeds such as fish meal, skim milk powder, casein, yellow grease, tallow, etc.; yeasts such as torula yeast and brewer's yeast; mineral feeds such as calcium phosphate and calcium carbonate; oils and fats; simple amino acids; sugars, etc.

When the composition of the present invention is in the form of a food or drink (including feed), it can be provided and sold as a food or drink labeled with a use for extending healthy lifespan.

Such "indication" acts include all acts aimed at informing consumers of the above-mentioned uses, and any expression that can recall or infer the above-mentioned uses falls under the category of "indication" acts in this invention, regardless of the purpose of the indication, the content of the indication, the object or medium on which it is displayed, etc.
Furthermore, it is preferable that the "labeling" be done in an expression that allows consumers to directly recognize the above-mentioned uses.Specific examples include the act of transferring, delivering, displaying for the purpose of transferring or delivering, or importing food and beverage products or product packaging on which the above-mentioned uses are written, displaying or distributing advertisements, price lists, or transaction documents related to the products and writing the above-mentioned uses in information containing the above-mentioned uses and providing them by electromagnetic means (such as the Internet), etc.

On the other hand, it is preferable that the content of the labeling be approved by the government or the like (for example, a labeling approved based on various systems established by the government and made in a manner based on such approval). It is also preferable that such content of the labeling be affixed to promotional materials at the point of sale such as packaging, containers, catalogs, pamphlets, and POP, as well as other documents, etc.

In addition, "labeling" also includes labeling as health food, functional food, enteral nutrition food, special purpose food, health functional food, food for specified health uses, nutrient functional food, functional food, quasi-drug, etc. Among these, in particular, labeling approved by the Consumer Affairs Agency, such as labeling approved under the system related to food for specified health uses, nutrient functional food, or food with functional labeling, or similar systems, can be mentioned. Specifically, labeling as food for specified health uses, labeling as food for conditional specified health uses, labeling that affects the structure or function of the body, labeling that reduces the risk of disease, labeling of functionality based on scientific evidence, etc., can be mentioned. More specifically, labeling as food for specified health uses (especially labeling of health uses) and similar labeling as specified in the Cabinet Office Ordinance on the Permission of Labeling for Special Purposes Provided in the Health Promotion Act (Cabinet Office Ordinance No. 57 of August 31, 2009) are typical examples.

Examples of such claims include "For those who want to extend their healthy lifespan," "To prevent and improve physical and mental aging," "Measures against frailty," and "Prevention of frailty."

The present invention will be explained in more detail below using examples, but the present invention is not limited to these examples.

[Test Example 1] Examination of the effect of extending healthy lifespan (1) Test method A test of administering the composition of the present invention to humans was carried out according to the following procedure. This test was carried out at Takara Clinic, Seishinkai Medical Corporation, with the approval of the clinic's ethics committee, in accordance with the spirit of the Declaration of Helsinki.
The subjects were Japanese men and women aged 65 or older who lived at home and had a bowel movement frequency of 2 to 5 times per week. The details of the study were fully explained to them, and informed consent was obtained. The following conditions were set as exclusion criteria for participation in the study. (a) Subjects currently undergoing treatment for or with a history of malignant tumors, (b) Subjects currently undergoing treatment for or with a history of autoimmune disease, (c) Subjects currently undergoing treatment for or with a history of inflammatory bowel disease, (d) Subjects currently hospitalized, (e) Subjects who regularly consume foods for specified health uses or foods with functional claims, (f) Subjects who regularly consume natto, yogurt, or foods/drinks containing lactic acid bacteria, (g) Smokers, (h) Subjects who regularly take anti-allergy medications, (i) Subjects who regularly take laxatives, (j) Subjects who regularly take supplements that may have functional properties other than foods for specified health uses or foods with functional claims, (k) Subjects with allergies (to medicines or foods related to the test food), (l) Subjects who are pregnant, breastfeeding, or intend to become pregnant during the study period, (m) Subjects who have participated in other clinical trials in the 3 months prior to the date of obtaining consent, (n) Subjects who the principal investigator deems inappropriate to be subjects of this study.
The intake group analyzed consisted of 28 people (10 men, 18 women, 71.0±4.5 years old).

The subjects were asked to take the test composition once a day after breakfast for four weeks. A non-taking group (29 subjects) was also set up in parallel, in which the subjects did not take the test composition.
The test composition is in powder form, and each dose (1.5 g) contains Bifidobacterium longum NI
It contained 10 billion live Lactobacillus paracasei NITE BP-02621 cells, 10 billion killed Lactobacillus paracasei NITE BP-01633 cells, 300 mg of lactulose, and 0.15 g of dietary fiber.
Before and 4 weeks after starting the intake, various subjective symptoms were evaluated by questionnaire (Likert scale method) on a 6-point scale: 1: not at all applicable, 2: hardly applicable, 3: not very applicable, 4: slightly applicable, 5: quite applicable, and 6: very applicable.
In addition, before and after 4 weeks of intake, body measurements and physical examinations were performed. As one of the measurements, muscle mass was measured using ZEUS 9.9 (manufactured by Kobe Medicare Co., Ltd.).

(2) Results: In the categories of "I'm worried about not being able to sleep,""I have no appetite," and "I still feel tired even after two days of rest," significant improvements were observed after taking the test composition compared to before (Table 1). In addition, in comparison with the non-taking group, the category of "I still feel tired even after two days of rest" was significantly improved (P<0.008).
A significant increase in muscle mass was observed after ingestion of the test composition compared to before ingestion (Table 2). A significant increase in muscle mass was also observed in comparison with the non-ingestion group (P<0.017).

Claims (3)

A composition for preventing and/or improving frailty, comprising live Bifidobacterium longum NITE BP-02621 bacteria, killed Lactobacillus paracasei NITE BP-01633 bacteria, and prebiotics . The composition of claim 1 , wherein the prebiotic is lactulose. The composition according to claim 1 or 2 , which is a food or drink.