Composition for suppressing cellular senescence

Abstract

To provide a composition that allows effective suppression of cellular senescence.SOLUTION: A composition for suppressing cellular senescence, comprising a lactic acid bacterium belonging to either the family Lactobacillaceae or the genus Streptococcus, is provided. Also provided is a composition for controlling expression of the sirtuin 1 (SIRT1) gene, comprising Lactiplantibacillus plantarum.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a composition for inhibiting cellular senescence. [Background technology]

[0002] It is known that human cells have a set number of divisions, and once that number is exceeded, they stop dividing. When cells stop dividing and become irreversibly unable to grow, this state is called cellular senescence. Cellular senescence is said to be a means of suppressing cancer.

[0003] Normally, cells that have stopped dividing are eliminated by immune cells. However, as the number of cells that have stopped dividing increases with aging, they cannot be eliminated in time and accumulate, attracting immune cells and releasing inflammatory cytokines. This condition is one of the causes of chronic inflammation associated with aging, which is thought to trigger conditions such as obesity, arteriosclerosis, and diabetes.

[0004] Regarding cellular aging, Patent Document 1 (JP 2021-112181 A) describes a composition for inhibiting the accumulation of senescent cells, which contains one or more species selected from the group consisting of Bifidobacterium bacteria, cultures of said bacteria, and processed products of said bacteria. Patent Document 2 (WO 2021 / 145113) describes an anti-aging composition containing Bifidobacterium longum NITE BP-02621, cultures of said bacteria, and processed products of said bacteria.

[0005] Meanwhile, the functions of lactic acid bacteria related to aging have been investigated. For example, Patent Document 3 (JP 2006-256993 A) describes an anti-aging agent containing the lactic acid bacterium Lactococcus lactis subsp. cremoris H-61 strain (NITE AP-92). Patent Document 4 (International Publication WO2019 / 098810 (JP 2006-256993 A, Japanese Patent No. 7242668)) describes Lactobacillus mucosae NK41 (Accession Number: KCCM12091P) and that the Lactobacillus mucosae NK41 inhibits the expression of the aging factor p16 protein. Patent Document 5 (JP Patent Publication No. 2020-59694 (Patent No. 6949906)) describes a longevity-promoting composition containing Lactobacillus plantarum, which is deposited at the China General Microbiological Culture Collection Center (No. 14565).Patent Document 6 (JP 2021-019507 A (JP Patent No. 6739603)) describes a composition for maintaining and / or improving memory and learning ability, which contains cells of heterofermentative lactobacillus bacteria of the genus Lactobacillus, and the maintenance and / or improvement of memory and learning ability is the prevention and / or improvement of a decline in memory and learning ability that occurs with aging (aging), and the decline in memory and learning ability that occurs with aging (aging) does not include a decline in memory and learning ability or a decline in memory ability that occurs with brain disease, memory disorders, and psychiatric disorders, and the heterofermentative lactobacillus bacteria of the genus Lactobacillus are Lactobacillus harbinensis species, Lactobacillus rhamnosus species, Lactobacillus casei species, Lactobacillus The present invention describes a composition for maintaining and / or improving memory and learning ability, which comprises one or a mixture of bacterial cells of multiple species of Lactobacillus casei, Lactobacillus paracasei, Lactobacillus fermentum, Lactobacillus mucosae, and Lactobacillus reuteri.

[0006] On the other hand, sirtuin genes (SIRT) are known to play an important role in controlling aging and lifespan. Mammals have seven sirtuin genes, SIRT1 to SIRT7. Patent Document 7 (Japanese Patent Laid-Open Publication No. 2008-81461) describes that kefir increases Sirt1 protein levels. Patent Document 8 (Japanese Patent Laid-Open Publication No. 2008-195673) describes lactic acid bacteria or components derived from lactic acid bacteria as life-prolonging substances characterized by enhancing the activity of sirtuin genes. Furthermore, Patent Document 9 (Japanese Patent Laid-Open Publication No. 2013-203669 (Patent No. 6066466)) describes the lactic acid bacteria Lactobacillus brevis T2102 strain (accession number NITE P-1274) and the SIRT1 transcription-enhancing effect of this bacterium. Furthermore, Non-Patent Document 1 describes that administering a combination of the L. plantarum 69-2 strain and galactooligosaccharides to D-galactose-induced aging mice exhibited high antioxidant activity and activated the AMPK / SIRT1 pathway in the liver. Furthermore, Non-Patent Document 2 describes that, among the offspring born to mice given L. rhamnosus GG during gestation, those colonized with L. rhamnosus GG had higher barrier function and activated the Sirt1 / AMPK / Pgc1-α pathway at 8 months of age than those not given L. rhamnosus GG, suggesting that colonization of L. rhamnosus GG during infancy may be effective in preventing age-related diseases. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Patent Publication No. 2021-112181 [Patent Document 2] International Publication WO2021 / 145113 [Patent Document 3] Japanese Patent Application Laid-Open No. 2006-256993 [Patent Document 4] JP 2021-112181 A (JP 2006-256993, Patent No. 7242668) [Patent Document 5] International Publication WO2021 / 145113 (Patent No. 6949906) [Patent Document 6] JP 2006-256993 A (Patent No. 6739603) [Patent Document 7] Patent Publication No. 2021-112181 [Patent Document 8] International Publication WO2021 / 145113 [Patent Document 9] JP 2006-256993 A (Patent No. 6066466) [Non-patent literature]

[0008] [Non-Patent Document 1] Wang et al., J Agric Food Chem. 2021 Mar 10;69(9):2745-2757. [Non-patent document 2] Liu et al., Oxid Med Cell Longev. 2021 Nov 11;2021:3328505. Summary of the Invention [Problem to be solved by the invention]

[0009] Inhibition of cellular senescence is believed to be effective for treating age-related diseases or conditions in which cellular senescence contributes, and therefore, means for controlling cellular senescence would be desirable. [Means for solving the problem]

[0010] The present invention provides the following: [1] A composition for inhibiting cellular aging, comprising lactic acid bacteria belonging to either the Lactobacillaceae family or the Streptococcus genus. [2] The composition according to 1, wherein the lactic acid bacteria are any of lactic acid bacteria belonging to the genus Lactiplantibacillus, Lacticaseibacillus, Companilactobacillus, Limosilactobacillus, Lactobacillus, Latilactobacillus, or Streptococcus. [3] The composition according to 1 or 2, wherein the lactic acid bacteria are any of lactic acid bacteria belonging to Lactiplantibacillus plantarum, Lactobacillus amylovorus, Lactobacillus helveticus, Lacticaseibacillus casei, Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus, Companilactobacillus farciminis, Limosilactobacillus fermentum, Limosilactobacillus reuteri, Limosilactobacillus oris, Lactobacillus johnsonii, Latilactobacillus sakei, or Streptococcus thermophilus. [4] The composition described in any one of 1 to 3, wherein the inhibition of cellular senescence is inhibition of cellular senescence of epithelial cells. [5] The composition described in any one of 1 to 4, wherein the inhibition of cellular senescence is inhibition of cellular senescence of intestinal epithelial cells. [6] A composition for regulating the expression of the Sirtuin 1 (SIRT1) gene, comprising Lactiplantibacillus plantarum. [7] The composition described in 6, wherein the expression control is suppression of decreased expression. [8] The composition described in any one of 1 to 7, which is for improving intestinal function that has declined due to aging. [9] The composition described in any one of 1 to 8, which is a food composition, a pharmaceutical composition, or a cosmetic composition.

[0011]

[11] A composition comprising lactic acid bacteria belonging to the family Lactobacillaceae or the genus Streptococcus for use in a method for inhibiting cellular senescence. Use of lactic acid bacteria belonging to the family Lactobacillaceae or the genus Streptococcus in the manufacture of a composition for inhibiting cellular senescence. A method or non-therapeutic method for inhibiting cellular senescence, comprising the step of administering to a subject a composition comprising lactic acid bacteria belonging to the family Lactobacillaceae or the genus Streptococcus. Use or non-therapeutic use of a composition comprising lactic acid bacteria belonging to the family Lactobacillaceae or the genus Streptococcus for inhibiting cellular senescence.

[12] The composition, use in production, method or non-therapeutic method, or use or non-therapeutic use according to 11, wherein the lactic acid bacteria are any of lactic acid bacteria belonging to the genus Lactiplantibacillus, Lacticaseibacillus, Companilactobacillus, Limosilactobacillus, Lactobacillus, Latilactobacillus, or Streptococcus.

[13] The composition, use in production, method or non-therapeutic method, or use or non-therapeutic use according to 11 or 12, wherein the lactic acid bacteria are any of lactic acid bacteria belonging to Lactiplantibacillus plantarum, Lactobacillus amylovorus, Lactobacillus helveticus, Lacticaseibacillus casei, Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus, Companilactobacillus farciminis, Limosilactobacillus fermentum, Limosilactobacillus reuteri, Limosilactobacillus oris, Lactobacillus johnsonii, Latilactobacillus sakei, or Streptococcus thermophilus.

[14] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to any one of claims 11 to 13, wherein the inhibition of cellular senescence is inhibition of cellular senescence of epithelial cells.

[15] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to any one of claims 11 to 14, wherein the inhibition of cellular senescence is inhibition of cellular senescence of intestinal epithelial cells.

[16] A composition comprising Lactiplantibacillus plantarum for use in a method for regulating the expression of the Sirtuin 1 (SIRT1) gene. Use of Lactiplantibacillus plantarum in the manufacture of a composition for regulating the expression of the Sirtuin 1 (SIRT1) gene. A method or non-therapeutic method for regulating the expression of the Sirtuin 1 (SIRT1) gene, comprising the step of administering a composition comprising Lactiplantibacillus plantarum to a subject. Use or non-therapeutic use of a composition comprising Lactiplantibacillus plantarum for regulating the expression of the Sirtuin 1 (SIRT1) gene.

[17] The composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to 16, wherein the expression control is suppression of decreased expression.

[18] A composition, use in manufacturing, method or non-therapeutic method, or use or non-therapeutic use according to any one of claims 11 to 17, wherein the composition is for improving intestinal function that has declined with age.

[19] The composition, use in manufacture, method or non-therapeutic method, or use or non-therapeutic use according to any one of claims 11 to 18, wherein the composition is a food composition, a pharmaceutical composition, or a cosmetic composition. [Effects of the Invention]

[0012] The composition of one embodiment controls cellular senescence.

[0013] According to one embodiment of the composition, cellular aging can be controlled using lactic acid bacteria cells, which are widely consumed. [Brief explanation of the drawings]

[0014] [Figure 1] SA-β-Gal activity during induction of cellular senescence is shown as mean ± SE (n = 4). *: p < 0.05, **: p < 0.01 (t-test, Bonferroni correction). [Figure 2] Mean cell number during induction of cellular senescence ± SE (n = 4). **: p < 0.01 (t-test, Bonferroni correction). [Figure 3] SIRT1 gene expression mean ± SE (n = 3). *: p < 0.05, **: p < 0.01 (t-test, Bonferroni correction). [Figure 4] The inhibitory effect of lactic acid bacteria on SA-β-Gal activity is shown in mean ± SE (n = 3). **: p < 0.01 (Dunnett's test). [Figure 5]16S rRNA gene, Lactiplantibacillus plantarum OLL2712 (SEQ ID NO:1), and 16S rRNA gene, Streptococcus thermophilus 1131 (SEQ ID NO:2) DETAILED DESCRIPTION OF THE INVENTION

[0015] This embodiment relates to a composition for inhibiting cellular aging, which contains a specific lactic acid bacterium as an active ingredient.

[0016] [Active ingredient] The composition of this embodiment contains either lactic acid bacteria belonging to the family Lactobacillaceae or the genus Streptococcus. Note that "either" refers to any type and any number of lactic acid bacteria.

[0017] In the present invention, when describing lactic acid bacteria belonging to the family Lactobacillaceae, unless otherwise specified, the classification follows the reclassification according to Zheng J, Wittouck S, Salvetti E, Franz CMAP, Harris HMB, Mattarelli P, O'Toole PW, Pot B, Vandamme P, Walter J, Watanabe K, Wuyts S, Felis GE, Ganzle MG, Lebeer S.: A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. Int J Syst Evol Microbiol. 2020 Apr; 70(4): 2782-2858.

[0018] (Lactic acid bacteria belonging to the Lactobacillaceae family) Lactic acid bacteria belonging to the family Lactobacillaceae include: Lactobacillus genus, Paralactobacillus genus, Holzapfelia genus, Amylolactobacillus genus, Bombilactobacillus genus, Companilactobacillus genus, Lapidilactobacillus genus, Agrilactobacillus genus, Schleiferilactobacillus genus, Loigolactobacilus genus, Lacticaseibacillus genus, Latilactobacillus genus, Dellaglioa genus, Liquorilactobacillus Liquorilactobacillus genus, Ligilactobacillus genus, Lactiplantibacillus genus, Furfurilactobacillus genus, Paucilactobacillus genus, Limosilactobacillus genus, Fructilactobacillus genus, Acetilactobacillus genus, Apilactobacillus genus, Levilactobacillus genus, Secundilactobacillus genus, Lentilactobacillus genus, Pediococcus The genera include the genera Convivina, Leuconostoc, Fructobacillus, Oenococcus, and Weissella.

[0019] In one embodiment, lactic acid bacteria belonging to any of the following genera among lactic acid bacteria belonging to the family Lactobacillaceae are used as the active ingredient. Genus Lactiplantibacillus, Genus Lacticaseibacillus, Genus Companilactobacillus, Genus Limosilactobacillus, Genus Lactobacillus

[0020] In a preferred embodiment, lactic acid bacteria belonging to any of the following species among the lactic acid bacteria belonging to the above genera are used as the active ingredient. Lactiplantibacillus plantarum, Lactobacillus amylovorus, Lactobacillus helveticus, Lacticaseibacillus casei, Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus, Companilactobacillus farciminis, Limosilactobacillus fermentum, Limosilactobacillus reuteri, Limosilactobacillus oris, Lactobacillus johnsonii, Latilactobacillus sakei

[0021] Various subspecies and strains of lactic acid bacteria belonging to the above genera can be used. For example, any of the following can be used. Lactiplantibacillus plantarum subsp.plantarum NCIMB 11974 T , Lacticaseibacillus casei JCM 1134 T , Companilactobacillus farciminis ATCC 29644 T , Limosilactobacillus fermentum NRIC 1752 T , Lactobacillus johnsonii JCM 2012 T, Lacticaseibacillus paracasei NBRC 15889 T , Limosilactobacillus reuteri JCM 1112 T , Lacticaseibacillus rhamnosus JCM 1136 T , Limosilactobacillus oris NCIMB 8831 T , Lactobacillus amylovorus JCM 1126 T , Lactobacillus helveticus JCM 1120 T , Latilactobacillus sakei JCM 1157 T

[0022] In a particularly preferred embodiment, the lactic acid bacteria used are those belonging to Lactiplantibacillus plantarum. More specifically, among the lactic acid bacteria belonging to Lactiplantibacillus plantarum, OLL2712 (hereinafter sometimes simply referred to as OLL2712) or a strain taxonomically identical thereto is used.

[0023] OLL2712 was internationally deposited with the National Institute of Advanced Industrial Science and Technology (National Institute of Advanced Industrial Science and Technology, Central No. 6, Higashi 1-1, Tsukuba City, Ibaraki Prefecture, Japan) on July 2, 2010, and has been assigned the accession number FERM BP-11262. As stated in Budapest Notification No. 282 (http: / / www.wipo.int / treaties / en / notifications / budapest / treaty_budapest_282.html), the Patent Organism Depositary of the National Institute of Advanced Industrial Science and Technology (IPOD, AIST) has transferred its patent microorganism deposit business to the National Institute of Technology and Evaluation (IPOD, NITE). As a result, OLL2712 is currently deposited at the National Institute of Technology and Evaluation (IPOD, NITE) (Room 120, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture) under the accession number FERM BP-11262 (depositor: Meiji Co., Ltd.).

[0024] The mycological properties of OLL2712 are shown below. Gram staining: positive, morphology: bacillus, lactic acid fermentation type: homolactic fermentation, aerobic growth: +, growth temperature: 15℃ +, 45℃ -. Colony shape: Diameter: 1-2 mm, Color: White, Shape: Round, Protrusion: Hemispherical, Rim: Entire, Surface shape: Smooth, Transparency: Opaque, Viscosity: Butter-like.

[0025] In the sequence listing, SEQ ID NO: 1 shows a partial sequence (533 bases long) of the 16S rRNA gene of OLL2712.

[0026] (Streptococcus) In one embodiment, lactic acid bacteria belonging to the genus Streptococcus are used as the active ingredient.

[0027] In a preferred embodiment, Streptococcus thermophilus (also known as Streptococcus salivarius subsp. thermophilus), a lactic acid bacterium belonging to the genus Streptococcus, is used as the active ingredient. More specifically, Streptococcus thermophilus 1131 or a strain taxonomically identical thereto is used.

[0028] S. thermophilus 1131 can be isolated from Meiji Bulgaria Yogurt LB81 (Meiji Co., Ltd.).

[0029] The mycological properties of 1131 are shown below. Morphology: Streptococcus, does not produce gas from glucose, gram-positive, catalase-negative, lactic acid rotatory L-form, grows at 45°C, produces acid by utilizing glucose, lactose, fructose, etc., does not form spores, is non-motile.

[0030] In the sequence listing, a partial sequence (489 bases long) of the 16S rRNA gene of 1131 is shown as SEQ ID NO:2.

[0031] (Lactic acid bacteria containing a specific gene and its ortholog) In one embodiment, the active ingredient is a lactic acid bacterium belonging to the family Lactobacillaceae or the genus Streptococcus, which has one of the polynucleotides set forth in SEQ ID NOS: 7 to 22 or its orthologs. More specifically, the active ingredient is a lactic acid bacterium having one or more, preferably two or more, more preferably four or more, even more preferably eight or more, and even more preferably all, of the polynucleotides consisting of the sequences of SEQ ID NOS: 7 to 22 or their orthologs. Alternatively, the active ingredient is a lactic acid bacterium having one of the proteins consisting of the sequences of SEQ ID NOS: 23 to 38 or its orthologs, more specifically, one or more, preferably two or more, more preferably four or more, even more preferably eight or more, and even more preferably all, of the proteins consisting of the sequences of SEQ ID NOS: 23 to 38 or their orthologs. According to the studies of the present inventors, among lactic acid bacteria, lactic acid bacteria expected to have an SA-β-Gal suppressing effect are thought to be, but are not limited to, lactic acid bacteria having a polynucleotide consisting of the sequences of SEQ ID NOS: 7 to 22 or its ortholog, and a protein consisting of the sequences of SEQ ID NOS: 23 to 38 or its ortholog. In the present invention, "ortholog" refers to a correspondence between genes derived from a common ancestral gene as a result of species divergence, or a group of genes in such a correspondence. Specifically, it refers to a group of genes or proteins that are grouped into the same orthogroup in Orthofinder (http: / / www.stevekellylab.com / software / orthofinder) (Genome Biol. 2015; 16(1): 157.).

[0032] Specifically, the polynucleotide set forth in any one of SEQ ID NOs: 7 to 22 or its ortholog is as follows: (A) a polynucleotide consisting of a sequence set forth in any one of SEQ ID NOs: 7 to 22; (B) a polynucleotide encoding a protein consisting of a sequence having a high sequence identity with any one of SEQ ID NOs: 7 to 22 and having the same activity as a protein consisting of the corresponding sequence of any one of SEQ ID NOs: 23 to 38; (C) A polynucleotide encoding a protein consisting of a sequence in which one or more nucleotides have been substituted, deleted, inserted, and / or added in any one of the sequences of SEQ ID NOs: 7 to 22, and having the same activity as a protein consisting of the corresponding sequence in any one of SEQ ID NOs: 23 to 38. A polynucleotide consisting of a sequence set forth in any one of SEQ ID NOs: 7 to 22 corresponds to a protein consisting of a sequence set forth in any one of SEQ ID NOs: 23 to 38, respectively.

[0033] In the context of the present invention, high sequence identity means that the sequence identity value is 70% or more, more preferably 80% or more, even more preferably 90% or more, even more preferably 95% or more, and even more preferably 98% or more.

[0034] In the present invention, unless otherwise specified, the term "identity" refers to the percentage of nucleotides that match between two sequences when the two sequences are aligned in an optimal manner. Searches and analyses of sequence identity can be performed using algorithms or programs well known to those skilled in the art, such as GENETIX (registered trademark) ver. 14 (Genetics Corporation), BLASTN, BLASTP, BLASTX, and ClustalW. When using a program, parameters can be appropriately set by those skilled in the art, or the default parameters of each program can be used. Specific techniques for these analysis methods are also well known to those skilled in the art.

[0035] (taxonomically identical strains) A strain taxonomically identical to a certain strain (hereinafter referred to as strain S) refers to, for example, any of the following: a strain belonging to the same species as strain S, the entire sequence of which or a characteristic part of which is a 16S rRNA gene (such as the V1 region, the V2 region, or all or part of the V1 and V2 regions, or a part including the V1 and V2 regions) has 90% or more, preferably 95% or more, more preferably 98% or more, even more preferably 98.5% or more, even more preferably 98.7% or more or higher, even more preferably 99% or more, more preferably 99.5% or more, and even more preferably 100% sequence identity with the sequence of strain S; A strain that belongs to the same species as strain S and has the same mycological properties as strain S. A strain belonging to the same species as strain S, in which the whole or a characteristic part of the sequence of its 16S rRNA gene (such as the V1 region, the V2 region, or all or part of the V1 and V2 regions, or a part including the V1 and V2 regions) has a sequence identity of 90% or more, preferably 95% or more, more preferably 98% or more, even more preferably 98.5% or more, even more preferably more than 98.7%, even more preferably 99% or more, more preferably 99.5% or more, and even more preferably 100% with the sequence of strain S, and which has the same mycological properties as strain S. A strain obtained by subculturing strain S and having the same mycological properties as strain S.

[0036] Regarding criteria for determining species identity based on 16S rRNA gene sequences, those skilled in the art can refer to Stackebrandt E, Ebers J. Taxonomic parameters revisited: tarnished gold standards. Microbiol Today 2006;33:152-155.

[0037] (manufacturing method, form, etc.) The lactic acid bacteria used in this embodiment can be produced by culturing. The culturing conditions are not particularly limited as long as the desired effect is achieved.

[0038] The lactic acid bacteria used may be contained in any state as long as they can exert the desired effect. For example, the lactic acid bacteria may be the lactic acid bacteria cells themselves, or a culture of lactic acid bacteria (consisting of lactic acid bacteria cells and culture supernatant). The cells may be in a live state (viable cells) or a dead state (dead cells) as long as they can exert the desired effect.

[0039] In one embodiment, the lactic acid bacteria are contained in the composition as killed cells. Killed cells can be obtained by sterilizing the lactic acid bacteria. The sterilization method is not particularly limited as long as it can achieve the desired effect, and can be heat, a germicidal lamp (UV), ozone, chemicals, high osmotic pressure, etc.

[0040] The killed bacteria are preferably heat-killed bacteria obtained by heat-treating live bacteria. The heat treatment for obtaining heat-killed bacteria is not particularly limited as long as the desired effect is achieved, and is carried out at a temperature and for a time sufficient to kill the lactic acid bacteria used. These conditions vary depending on the lactic acid bacteria used, but are, for example, 55°C or higher, preferably 60°C or higher, more preferably 65°C or higher, and even more preferably 70°C or higher, and may be 80°C or higher, or even 90°C or higher. The upper limit of the heat treatment temperature can be set appropriately, for example, 121°C or lower, 100°C or lower, 90°C or lower, or 80°C or lower. Depending on the heat treatment temperature, the heat treatment time can be 1 minute or more, 3 minutes or more, 10 minutes or more, 15 minutes or more, 30 minutes or more, or 45 minutes or more. The upper limit of the heat treatment temperature can be, for example, 120 minutes or lower, 100 minutes or lower, 90 minutes or lower, or 80 minutes or lower.

[0041] The lactic acid bacteria to be contained in the composition can be prepared in the form of a dry product, suspension, paste, gel, or the like, regardless of whether they are live or dead cells.

[0042] [Application] (Action / Function) The composition of this embodiment can be used to inhibit cellular senescence.

[0043] Cellular senescence is a state in which cells cease division and irreversibly become unable to proliferate. Cellular senescence can be indicated by morphological and metabolic changes (e.g., increased activity of senescence-associated β-galactosidase (SA-β-Gal) and cell morphology (becoming larger and flatter), and increased intracellular reactive oxygen species (ROS) levels), cell cycle arrest (e.g., p21 Cip1 / Waf , p16 INK4α It can be evaluated by measuring the level of cellular senescence (e.g., p53, telomere shortening), DNA damage and persistent DNA damage response (e.g., phosphorylation of Ser139 of H2A.X can be used as an indicator), and senescence-associated secretory phenotype (SASP) (e.g., IL-6, TNFα, HMGB1, IL-1β can be used as indicators).

[0044] While cellular senescence in the composition of this embodiment can be assessed by any of the methods described above, in one aspect, the cellular senescence is cellular senescence that can be indexed by SA-β-Gal activity, which is widely used as a marker for detecting senescent cells.

[0045] Whether a certain component can inhibit cellular senescence can be evaluated, for example, by inducing cellular senescence in appropriate cultured cells using a reagent and then confirming whether cellular senescence is inhibited in the presence of the component to be evaluated. Reagents that can induce cellular senescence include doxorubicin (DXR) and its salts, hydroxyurea (HU), and D-galactose. DXR and HU both inhibit DNA synthesis and arrest the cell cycle, mimicking the state of cellular senescence. Whether cellular senescence is inhibited can be evaluated by measuring the aforementioned SA-β-Gal activity. An example of cultured cells that can be used is Caco-2 cells.

[0046] In one embodiment, the composition is used to inhibit cellular senescence in specific cells. The cells are not particularly limited, and may be, for example, epithelial cells. Epithelial cells are present on the surface of the body (skin), body cavities (intestinal tract), organs, etc., and also constitute exocrine and endocrine glands. By inhibiting cellular senescence in epithelial cells, the composition can be used to prevent or improve functional decline, etc., of various epithelial cells.

[0047] In a preferred embodiment, the composition is used to inhibit cellular senescence in intestinal epithelial cells. Cellular senescence in intestinal epithelial cells can be a type of intestinal aging. Intestinal aging generally refers to the decrease in bifidobacteria and the increase in harmful bacteria due to aging, as well as the decrease in peristaltic movement, the decrease in the contractile force of the anal sphincter, and the decrease in abdominal pressure due to aging. Inhibition of cellular senescence in intestinal epithelial cells can improve impaired intestinal function. Improvement of impaired intestinal function due to aging includes improvement of decreased digestive and absorptive capacity and decreased peristaltic movement.

[0048] In the present invention, the intestine refers to the digestive organ in humans and animals where bacteria normally reside and which digests and absorbs ingested food. The intestine includes the small intestine and the large intestine, and is preferably the small intestine.

[0049] The composition of this embodiment can be used to regulate the expression of the SIRT1 gene. Regulation includes upregulation (e.g., inhibition of increase, promotion, elevation, enhancement, decrease, etc.) and downregulation (e.g., inhibition of decrease, decrease, increase, etc.). In this case, lactic acid bacteria belonging to Lactiplantibacillus plantarum can be used as a particularly preferred active ingredient. Mammals have seven types of sirtuins, SIRT1 to SIRT7, and of these, SIRT1 is thought to be involved in the control of aging and lifespan.

[0050] The expression of the SIRT1 gene can be evaluated by transcription into mRNA and translation into protein. The control of SIRT1 gene expression is preferably suppression of a decrease in SIRT1 gene expression or enhancement (promotion) of SIRT1 gene expression.

[0051] Uses of the composition of this embodiment may exclude any use selected from the group consisting of: Amelioration of lipopolysaccharide (LPS)-induced intestinal inflammation, suppression of LPS-induced increase in intestinal permeability, and prevention of LPS-induced intestinal barrier dysfunction; Suppression of the decline in intestinal epithelial barrier function, restoration of barrier function, protection from increased mucosal permeability associated with dextran sulfate sodium-induced colitis, treatment of gastrointestinal diseases such as inflammatory bowel disease; Prevention and treatment of alcohol-induced tissue damage (destruction of colonic tight junctions, impaired intestinal mucosal barrier function, liver damage), especially alcoholic hepatitis; In Salmonella-infected intestinal epithelial cells (IECs), the expression of membrane ATG16L1 protein is mediated by the promotion of autophagy and the suppression of inflammatory IL-1β expression, thereby treating infectious diseases and autoimmune diseases. Treatment of gluten-specific enteropathy, recovery from specific toxic parameters induced by gluten in enteritis.

[0052] (subject) The composition of this embodiment is suitable for administration to subjects for whom it is desirable to control cellular senescence, particularly subjects for whom it is desirable to suppress intestinal senescence (more particularly, subjects for whom it is desirable to control cellular senescence in intestinal epithelial cells, subjects for whom it is believed that SIRT1 expression is reduced). It is also suitable for administration to subjects for whom it is desirable to improve impaired intestinal function, subjects for whom it is desirable to improve impaired digestive and absorptive capacity, and subjects for whom it is desirable to improve impaired peristalsis. It is preferable that all subjects are healthy (e.g., free of intestinal disease, infection, and / or cancer).

[0053] The composition of this embodiment is also suitable for use in controlling cellular senescence in healthy subjects, particularly for controlling cellular senescence in the intestine of healthy subjects (more particularly, for controlling cellular senescence in intestinal epithelial cells). The composition of this embodiment can be used non-therapeutically. "Non-therapeutic" means not intended to treat a disease. In the context of the present invention, "healthy" refers to not having an infectious disease, not having cancer, or not having an infectious disease or cancer, unless otherwise specified. A doctor can determine that a patient is not having an infectious disease, not having cancer, or not having an infectious disease or cancer. An infectious disease refers to a state in which symptoms such as pain, inflammation, and fever are present due to infection with a pathogen.

[0054] The subjects include adults (15 years of age or older), middle-aged and elderly people, elderly people (65 years of age or older), those currently in the midst of illness, pregnant women, women who have just given birth, infants, and children. Furthermore, the composition of this embodiment is suitable for long-term ingestion because the active ingredient is a lactic acid bacterium that has a long history of consumption.

[0055] The composition of this embodiment is also suitable for use in promoting SIRT1 expression in obese individuals (Int J Obes (Lond). 2016 Nov;40(11):1635-1642. doi: 10.1038 / ijo.2016.131.), and for suppressing cellular senescence of vascular endothelial cells in individuals with arteriosclerosis or hypertension (J Physiol. 2016 Apr 15;594(8):2115-24. doi: 10.1113 / JP270923.).

[0056] [Composition] (Food composition, etc.) The composition of this embodiment can be a food composition, pharmaceutical composition, or cosmetic composition. Foods, pharmaceuticals, and cosmetics include not only those for humans but also those for non-human animals, unless otherwise specified. Foods, unless otherwise specified, 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 therapeutic support. Foods, unless otherwise specified, include not only solid foods but also liquid foods, such as beverages, energy drinks, liquid foods, and soups. Functional foods refer to foods that can impart specific functionality to the 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 functions, foods for special dietary uses, dietary supplements, health supplements, supplements (e.g., tablets, coated tablets, sugar-coated tablets, capsules, liquids, etc.), and beauty foods (e.g., diet foods). Furthermore, in the present invention, "functional foods" also encompasses health foods to which a health claim based on the Codex Alimentarius (the Joint FAO / WHO Food Standards Commission) is applied. In the present invention, pharmaceuticals include topical skin preparations. In the present invention, cosmetics include quasi-drugs and include both cosmetics that do not contain active ingredients and medicated cosmetics that contain active ingredients.

[0057] (Route of administration) The composition of this embodiment may be administered orally, parenterally, for example, via a tube (gastrostomy, enterostomy), or intranasally. It may also be administered transdermally. In the context of the present invention, "administer" refers not only to administering a pharmaceutical to a subject, but also to ingestion of food by a subject or application of cosmetics to the skin. "Administer" can sometimes be read as "intake" and "ingestion" can also be read as "administer."

[0058] (Active ingredient content and dosage) The content of the active ingredient in the composition of this embodiment may be any amount that can achieve the desired effect. The content of lactic acid bacteria in the composition can be appropriately determined taking into consideration various factors such as the age, weight, and symptoms of the subject to be ingested or administered. The content of lactic acid bacteria per unit of the composition can be, for example, 1 x 10 6 Can be more than 1 x 10 7 Can be more than 1 x 10 8 More than 5×10 8 pcs or more, 1×10 9 More than 5×10 9 It can be more than 1 x 10 10 It is preferable to have more than 1×10 11 More preferably, 2×10 11 The upper limit can be set appropriately, and whatever the lower limit, for example, 1 × 10 14 It may be less than 1 x 10 13 It may be less than 1 x 10 12 One unit of the composition can be taken by the subject once per day, or it can be taken by the subject multiple times per day, for example, three times.

[0059] The content of lactic acid bacteria per 1 g of the composition is, for example, 1 × 10 4 Can be more than 1 x 10 6 pcs or more, 1×10 7 pcs or more, 1×10 8 pcs or more, 1×10 9 It can be more than 5 x 10 9 The upper limit can be set appropriately, and whatever the lower limit, for example, 1 × 10 14 It may be less than 1 x 10 13 It may be less than 1 x 10 12 It may be less than one.

[0060] Furthermore, when the lactic acid bacteria content is as described above, in either case, one unit can be, for example, 0.5 g or more, 1 g or more, 5 g or more, 10 g or more, 20 g or more, or 30 g or more. When the composition is in the form of a food such as fermented milk, one unit can be an amount that is easy to ingest as a food in one sitting, for example, 50 g or more, 60 g or more, 70 g or more, 80 g or more, 90 g or more, or 100 g or more. The upper limit can be set as appropriate, and in either case, the lower limit can be set to 500 g or less, 400 g or less, 300 g or less, 200 g or less, 150 g or less, or 125 g or less.

[0061] The composition of this embodiment contains lactic acid bacteria that have been consumed extensively as an active ingredient, and therefore, the composition of this embodiment may be administered repeatedly or over a long period of time, for example, for three days or more, preferably one week or more, more preferably four weeks or more, and particularly preferably one month or more.

[0062] (Other ingredients, additives) The composition of this embodiment may contain ingredients acceptable for food, medicine, or cosmetics. Examples of ingredients acceptable for food or medicine 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), kojibiose, and kojibiose-containing sugars. Examples of ingredients that are acceptable for cosmetics include carbohydrates other than oligosaccharides (glucose, sucrose, fructose, maltose, trehalose, erythritol, maltitol, palatinose, xylitol, dextrin), electrolytes (e.g., sodium, potassium, calcium, 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, manganese), antibiotics, dietary fiber, etc. Examples of ingredients that are acceptable for cosmetics include aqueous ingredients, oily ingredients, powder ingredients, alcohols, moisturizing ingredients, fragrances, pigments, etc.

[0063] The composition of this embodiment may further contain additives acceptable for use as foods, pharmaceuticals, or cosmetics. Examples of such additives include 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, water-soluble dextran, water-soluble dextrin, sodium carboxymethyl starch, pectin, xanthan gum, gum arabic, casein, gelatin, agar, glycerin, propylene glycol, polyethylene glycol, petrolatum, paraffin, stearyl alcohol, stearic acid, human serum albumin, mannitol, sorbitol, lactose, sucralose, stevia, aspartame, acesulfame potassium, citric acid, lactic acid, malic acid, tartaric acid, phosphoric acid, acetic acid, fruit juice, and vegetable juice.

[0064] (Dosage form / shape) In one embodiment, the food composition may be prepared in any form, such as a solid, liquid, mixture, suspension, powder, granules, paste, jelly, gel, capsule, etc. The food composition of the present invention may also be prepared in any form, such as dairy products, supplements (e.g., tablets, coated tablets, sugar-coated tablets, enteric-coated agents, capsules (enteric-coated soft capsules, enteric-coated hard capsules, colon-delivery capsules, etc.)), confectioneries, beverages, energy drinks, seasonings, processed foods, prepared dishes, soups, etc. More specifically, the composition of this embodiment can be in the form of a liquid food, semi-liquid food, jelly, gel, powder, infant formula, infant formula, powdered or liquid milk for pregnant or nursing women, fermented milk, bar, mousse, chocolate, biscuit, ice cream, fermented milk, lactic acid bacteria drink, dairy drink, dairy beverage, soft drink, fruit juice drink, tablet, cheese, bread, biscuit, cracker, pizza crust, food for the sick, nutritional food, frozen food, processed food, etc. It can also be in the form of granules, powder, paste, thickened liquid, etc. to be mixed with beverages or foods for administration. The granules and powder can be in the form of cubes or sticks (single-serving amounts packaged). In the present invention, modified powdered milk refers to a powdered product obtained by processing raw milk, cow's milk, special cow's milk, or raw buffalo milk, or a food made from any of these ingredients, or by using these as the main ingredient, and adding nutrients necessary for infants, as defined in the Ministerial Ordinance on Milk, etc. In the present invention, modified liquid milk refers to a liquid product obtained by processing raw milk, cow's milk, special cow's milk, or raw buffalo milk, or a food made from any of these ingredients, or by using these as the main ingredient, and adding nutrients necessary for infants, as defined in the Ministerial Ordinance on Milk, etc.

[0065] In one embodiment, the pharmaceutical composition can be in any dosage form suitable for oral administration, such as solid preparations such as tablets, granules, powders, pills, and capsules (enteric-coated soft capsules, enteric-coated hard capsules, colon delivery capsules, etc.); liquid preparations such as solutions, suspensions, and syrups; gels; and aerosols. The solid preparations can be coated or sugar-coated, and can be enterically treated by enteric coating or the like. Furthermore, the pharmaceutical composition can be in the form of ointments, creams, topical liquid preparations, eye drops, nasal drops, suppositories, patches, or inhalants suitable for topical administration.

[0066] In one embodiment, the cosmetic composition can be in the form of a solution, emulsion, suspension, gel, cream, mask pack, sheet, foam, or aerosol.

[0067] (others) In the production of the composition of this embodiment, the stage of blending the active ingredients 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 ingredients. For example, each raw material (acidulant, sweetener, stabilizer, fruit juice, flavoring, lactic acid bacteria cells, water) and a heat-treated predetermined lactic acid bacteria (about 10 9 The resulting mixture is suspended in ion-exchanged water and heated at 95°C for 3 minutes. The mixture is mixed and bottled to prepare a composition in the form of a 100 mL fruit juice-flavored soft drink.

[0068] In one embodiment, the composition can be labeled with its intended use (application), and in another embodiment, the function of the composition or active ingredient or a usage based on that function is labeled. Examples of usage based on the function are as described above for functions, actions, and effects. Furthermore, the composition of this embodiment can be labeled with its use as a prebiotic or as a synbiotic (a combination of probiotics and prebiotics). Examples of such labeling include "inhibition of cellular aging," "inhibition of senescent cell formation," "prevention of cellular aging," "prevention of senescent cell formation / proliferation," "inhibition of senescent cell proliferation," or "inhibition of cellular aging in the intestine," "prevention of cellular aging in the intestine," "prevention of senescent cell formation / proliferation in the intestine," "inhibition of senescent cell proliferation in the intestine," "inhibition of cellular aging in the skin," "prevention of cellular aging in the skin," "prevention of senescent cell formation / proliferation in the skin," "inhibition of senescent cell proliferation in the skin," "maintenance of intestinal and skin health," etc. Suppression includes preventing the onset, delaying the onset, reducing the incidence, reducing the risk of onset, etc. Amelioration of a condition or disease includes recovering from a condition or disease, alleviating (preferably temporarily alleviating) the symptoms of a condition or disease, improving the symptoms of a condition or disease, delaying or preventing the progression of a condition or disease, etc.

[0069] In one embodiment, the composition is labeled to recommend administration to a specific subject. Examples of subjects for which the labeling is provided are as described above for subjects.

[0070] 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.

[0071] The present invention will now be described in more detail with reference to examples. [Example]

[0072] [Example 1] (Preparation of OLL2712) Lactiplantibacillus plantarum OLL2712 was cultured in MRS medium for 18 hours, the culture was suspended in DW, heated at 75°C for 60 minutes, and then freeze-dried. The freeze-dried cells were suspended in DW at 100 μg / mL (approximately 3 × 10 8 cfu / mL) were added to the cells.

[0073] (SA-β-Gal activity measurement / viable cell count measurement) Caco-2 cells (RIKEN BioResource Research Center) were cultured at 1 × 10 in a 96-well plate. 4 Cells were seeded at 1000 cells / well and stimulated the following day with 10 μM doxorubicin (DXR) (doxorubicin hydrochloride, Fujifilm Wako Pure Chemical Industries, Ltd. #040-21521) or 1 mM hydroxyurea (HU) (Sigma #H8627-1G) and OLL2712. After 24 hours, cell numbers were measured using the Cell Count Normalization Kit (Dojindo Laboratories #C544), followed by measurement of senescence-associated β-galactosidase (SA-β-Gal) activity using the Cellular senescence plate assay kit (Dojindo Laboratories #SG05). The measured SA-β-Gal activity was normalized for cell number and compared.

[0074] DXR and HU significantly induced (increased) SA-β-Gal activity, but OLL2712 significantly inhibited this induction (increase) of SA-β-Gal activity (Figure 1). Furthermore, a comparison of the measured cell counts revealed that DXR significantly decreased cell counts, but OLL2712 stimulation inhibited this decrease (Figure 2). These findings suggest that OLL2712 inhibits cellular senescence and the associated decrease in cell proliferation.

[0075] (SIRT1 gene expression) Caco-2 cells were plated in a 48-well plate at 3 × 104 The cells were seeded at 1000 cells / well and stimulated the next day with DXR 10 μM or HU 1 mM and OLL2712. After 18 hours, the cells were harvested, RNA was extracted, and the expression levels of SIRT1 were compared by real-time PCR. The primers used were as follows:

[0076] hGAPDH: forward 5'-GCACCGTCAAGGCTGAGAAC-3'(SEQ ID NO:3) reverse 5'-TGGTGAAGACGCAGTGGA-3' (SEQ ID NO:4) hSIRT1: forward 5'-TAGCCTTGTCAGATAAGGAAGGA-3' (SEQ ID NO:5) reverse 5'-ACAGCTTCACAGTCAACTTTGT-3' (SEQ ID NO:6)

[0077] DXR significantly reduced SIRT1 expression, but this reduction was suppressed by OLL2712 stimulation. HU did not reduce SIRT1 expression, but OLL2712 stimulation significantly increased its expression (Figure 3). These results suggest that OLL2712 suppresses the reduction of SIRT1 expression or enhances its expression, thereby suppressing cellular senescence.

[0078] (summary) From the above, it can be said that lactic acid bacteria belonging to Lactiplantibacillus plantarum can control cell aging in epithelial cells and also control the expression of the SIRT1 gene.

[0079] [Example 2] (Preparation of bacterial cells) The strains listed in Table 1 were cultured in MRS medium or M17 medium supplemented with 1% lactose at 30°C or 37°C (according to Table 1) for 18 hours, and the cultures were suspended in DW, heated at 75°C for 60 minutes, and then freeze-dried. The freeze-dried cells were suspended in DW at 100 μg / mL (approximately 3 × 10 8cfu / mL) were added to the cells.

[0080] (SA-β-Gal activity measurement) Caco-2 cells were plated at 1 × 10 in a 96-well plate. 4 The following day, cells / well were stimulated with 10 μM DXR and the bacterial strains listed in Table 1. 24 hours later, SA-β-Gal activity was measured using a Cellular senescence plate assay kit (Dojindo #SG05). SA-β-Gal activity was normalized by cell count determined using a Cell Count Normalization Kit (Dojindo #C544).

[0081] When SA-β-Gal activity normalized for cell number was compared, DXR-induced SA-β-Gal activity was significantly suppressed by stimulation with the bacteria listed in the table below (Figure 4). These findings suggest that various lactic acid bacteria have the effect of suppressing cell aging.

[0082] [Table 1]

[0083] (summary) From the above, it can be said that various lactic acid bacteria belonging to the Lactobacillaceae family or the Streptococcus genus can control cellular aging.

[0084] [Method for measuring SA-β-Gal activity and cell count] The cell number was measured using the Cell Count Normalization Kit (Dojindo #C544), and then SA-β-Gal activity was measured using the Cellular senescence plate assay kit (Dojindo #SG05). 1. 1 x 10 cells in a 96-well plate 4 Add 100 μL / well of working solution (x500) to cells seeded at 100 cells / well. 2. Incubate in a CO2 incubator for 30 minutes 3. Remove the entire supernatant and wash twice with PBS. 4. Add 100 μL of Dilution buffer to each well. 5. Measure the wavelengths of Ex:Em = 350 nm:461 nm using a fluorescent plate reader (cell count measurement). Wash the plate from step 6.5 once with PBS. 7. Add 50 μL of lysis buffer per well and let stand at room temperature for 10 minutes. 8. Add 50 μL / well of SPiDER-β-Gal working solution (x10) and incubate at 37°C for 30 minutes. 9. Add 100 μL of stop solution to each well 10. Measure the wavelengths of Ex:Em = 535 nm:580 nm using a fluorescent plate reader. 11. Correct the obtained SPiDER-β-Gal fluorescence intensity with the fluorescence value of the nucleic acid stain measured in 5 to calculate SA-β-Gal activity.

[0085] [Genetic analysis] (method) Gene sequences common to bacteria that are expected to have an SA-β-Gal inhibitory effect were extracted by analyzing the consensus sequences of the lactic acid bacteria strains in the table below.

[0086] The reference strain (NCIMB 11974 T , JCM 1134 T , ATCC 29644 T , JCM 2012 T , NBRC 15889 T , JCM 1112 T The whole genome sequence of each strain was obtained as a FASTA file (a file containing the whole genome sequence). For Limosilactobacillus fermentum P2303205, the reference strain NRIC 1752, which has a 16S rRNA gene sequence very similar to that of P2303205, was used. TThe whole genome sequence of the gene (presumed to have an SA-β-Gal suppression effect) was obtained from the NCBI database.

[0087] The FASTA files containing the whole genome sequences of each strain were uploaded to DFAST ( 1709082816715_0 ) and prepared a file containing the protein and amino acid sequences. For the strains in the table below that have SA-β-Gal inhibitory activity, the process of extracting orthologs between two strains from their amino acid sequence information was repeated to extract sequences shared only by the active strains. Orthologs were extracted from the amino acid sequence information of the strains with SA-β-Gal inhibitory activity, and the amino acid sequences shared by at least one lactic acid bacteria strain that does not have the SA-β-Gal inhibitory effect were removed to determine the "common genes shared only by the active strains." Orthologs were grouped into the same orthogroup using Orthofinder (http: / / www.stevekellylab.com / software / orthofinder).

[0088] [Table 2]

[0089] The nucleotide sequences of the common genes thus obtained and the amino acid sequences of the corresponding proteins are shown in the sequence listing as SEQ ID NOS: 7 to 22 and 23 to 38.

[0090] (summary) From the above, it is thought that lactic acid bacteria that can be expected to have an SA-β-Gal inhibitory effect are lactic acid bacteria that have a gene or its ortholog consisting of the sequences of SEQ ID NOs: 7 to 22, or a protein or its ortholog consisting of the sequences of SEQ ID NOs: 23 to 38, but are not limited to these.

[0091] [Sequence listed in the sequence listing]

[0092] SEQ ID NO:1 Partial sequence of 16S rRNA gene of Lactiplantibacillus plantarum OLL2712(FERM BP-11262) SEQ ID NO:2 Partial sequence of 16S rRNA gene of Streptococcus thermophilus 1131 SEQ ID NO:3 PCR primer SEQ ID NO:4 PCR primer SEQ ID NO:5 PCR primer SEQ ID NO:6 PCR primer SEQ ID NO:7 polynucleotide encoding MGA_1083_1131_10770 unnamed protein product SEQ ID NO:8 polynucleotide encoding MGA_1108_1131_11020 unnamed protein product SEQ ID NO:9 polynucleotide encoding MGA_1331_1131_13250 unnamed protein product SEQ ID NO:10 polynucleotide encoding MGA_1428_1131_14220 unnamed protein product SEQ ID NO:11 polynucleotide encoding MGA_1455_1131_14490 unnamed protein product SEQ ID NO:12 polynucleotide encoding MGA_1644_1131_16380 unnamed protein product SEQ ID NO:13 polynucleotide encoding MGA_1651_1131_16450 unnamed protein product SEQ ID NO:14 polynucleotide encoding MGA_1938_1131_19310 unnamed protein product SEQ ID NO:15 polynucleotide encoding MGA_214_1131_02100 unnamed protein product SEQ ID NO:16 polynucleotide encoding MGA_465_1131_04600 unnamed protein product SEQ ID NO:17 polynucleotide encoding MGA_526_1131_05210 unnamed protein product SEQ ID NO:18 polynucleotide encoding MGA_582_1131_05770 unnamed protein product SEQ ID NO:19 polynucleotide encoding MGA_732_1131_07260 unnamed protein product SEQ ID NO:20 polynucleotide encoding MGA_76_1131_00730 unnamed protein product SEQ ID NO:21 polynucleotide encoding MGA_893_1131_08870 unnamed protein product SEQ ID NO:22 polynucleotide encoding MGA_998_1131_09920 unnamed protein product SEQ ID NO:23 MGA_1083_1131_10770 unnamed protein product SEQ ID NO:24 MGA_1108_1131_11020 unnamed protein product SEQ ID NO:25 MGA_1331_1131_13250 unnamed protein product SEQ ID NO:26 MGA_1428_1131_14220 unnamed protein product SEQ ID NO:27 MGA_1455_1131_14490 unnamed protein product SEQ ID NO:28 MGA_1644_1131_16380 unnamed protein product SEQ ID NO:29 MGA_1651_1131_16450 unnamed protein product SEQ ID NO:30 MGA_1938_1131_19310 unnamed protein product SEQ ID NO:31 MGA_214_1131_02100 unnamed protein product SEQ ID NO:32 MGA_465_1131_04600 unnamed protein product SEQ ID NO:33 MGA_526_1131_05210 unnamed protein product SEQ ID NO:34 MGA_582_1131_05770 unnamed protein product SEQ ID NO:35 MGA_732_1131_07260 unnamed protein product SEQ ID NO:36 MGA_76_1131_00730 unnamed protein product SEQ ID NO:37 MGA_893_1131_08870 unnamed protein product SEQ ID NO:38 MGA_998_1131_09920 unnamed protein product

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[0093] The present invention can support the maintenance and improvement of people's health by providing a composition for inhibiting cellular aging, which contains lactic acid bacteria belonging to either the Lactobacillaceae family or the Streptococcus genus. 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 lifestyles, and promote welfare.

Claims

1. A composition for inhibiting cellular aging, comprising lactic acid bacteria belonging to either the Lactobacillaceae family or the Streptococcus genus.

2. 2. The composition according to claim 1, wherein the lactic acid bacteria are any of lactic acid bacteria belonging to the genus Lactiplantibacillus, Lacticaseibacillus, Companilactobacillus, Limosilactobacillus, Lactobacillus, Latilactobacillus, or Streptococcus.

3. The composition according to claim 1, wherein the lactic acid bacteria are any of Lactiplantibacillus plantarum, Lactobacillus amylovorus, Lactobacillus helveticus, Lacticaseibacillus casei, Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus, Companilactobacillus farciminis, Limosilactobacillus fermentum, Limosilactobacillus reuteri, Limosilactobacillus oris, Lactobacillus johnsonii, Latilactobacillus sakei, and Streptococcus thermophilus.

4. The composition according to claim 1 , wherein the inhibition of cellular senescence is inhibition of cellular senescence of epithelial cells.

5. The composition according to claim 1 , wherein the inhibition of cellular senescence is inhibition of cellular senescence of intestinal epithelial cells.

6. A composition for regulating the expression of Sirtuin 1 (SIRT1) gene, comprising Lactiplantibacillus plantarum.

7. The composition according to claim 6 , wherein the expression control is suppression of decreased expression.

8. The composition according to any one of claims 1 to 3, 6 and 7, which is for improving intestinal function that has declined with age.

9. The composition according to claim 1, which is a food composition, a pharmaceutical composition, or a cosmetic composition.

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