Application of saccharomyces cerevisiae and metabolites thereof in preparation of anti-aging products

Abstract

The invention discloses application of saccharomyces cerevisiae and metabolites thereof in preparation of anti-aging products. The saccharomyces cerevisiae is screened out from a saccharomyces cerevisiae single-gene mutant strain library, and the saccharomyces cerevisiae lacks one of genes with nucleotide sequences shown as SEQ ID NO.1-14. The invention further discloses a preparation method of the saccharomyces cerevisiae. The yeast gene engineering strain and the metabolite thereof have the functions of remarkably prolonging the life, improving the exercise ability and the intestinal integrity of an old person and delaying the aging of the body; in addition, standardized production of the strain can be realized.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to the application of brewer's yeast and its metabolites in the preparation of anti-aging products. Background Art

[0002] As the problem of global population aging intensifies, anti-aging research has become a hot topic in biology, medicine and biotechnology. In recent years, scientists have been exploring the secrets of anti-aging, hoping to delay the human aging process and improve the quality of life through scientific means. However, this research faces many challenges and difficulties. Among the many anti-aging research approaches, the use of genetic engineering technology to transform microbial strains to prepare products with anti-aging effects is a very promising direction. Yeast, as a common model organism, has broad application prospects in the field of genetic engineering. Transforming yeast through genetic engineering technology can produce substances with anti-aging activity, such as antioxidants, anti-inflammatory factors, etc., which are of great value in the development of anti-aging products.

[0003] However, there are many technical challenges to be solved in current anti-aging research. The first is how to accurately locate and transform genes related to yeast aging to develop genetically engineered probiotics and achieve efficient expression of anti-aging substances. This urgent problem needs to be solved. Summary of the invention

[0004] The purpose of the present invention is to provide the use of brewer's yeast and its metabolites in the preparation of anti-aging products. The present invention utilizes genetic engineering technology to transform yeast strains so that they can efficiently express functional ingredients that have the function of delaying the aging process of the human body; the brewer's yeast has the functions of significantly prolonging lifespan, improving the motor ability and intestinal integrity function of elderly individuals, and delaying the aging of the body; in addition, the strain can also achieve standardized production.

[0005] To achieve the above object, the present invention provides an application of Saccharomyces cerevisiae and its metabolites in the preparation of anti-aging products, wherein the Saccharomyces cerevisiae is screened from a Saccharomyces cerevisiae gene-knockout strain library, and the Saccharomyces cerevisiae gene-knockout strain library is purchased from Invitrogen. The Saccharomyces cerevisiae gene-knockout collection (YKOC) is a resource library containing a large number of gene knockout mutants, which covers 6,000 genes in the Saccharomyces cerevisiae genome. The present invention can significantly improve the aging degree of the host and prolong life by screening 14 mutant genes from the gene knockout library.

[0006] The brewer's yeast lacks one of the genes YJR044C, YDR176W, YPL257W, YCL051W, YAL053W, YAL044C, YER164W, YPL253C, YER169W, YBR041W, YNL125C, YER174C, YML088W, and YLL015W; the nucleotide sequences of the YJR044C, YDR176W, YPL257W, YCL051W, YAL053W, YAL044C, YER164W, YPL253C, YER169W, YBR041W, YNL125C, YER174C, YML088W, and YLL015W are shown in SEQ ID NOs.1-14.

[0007] Preferably, the product is used to improve athletic performance.

[0008] Preferably, the product is used to improve the integrity of the intestinal barrier.

[0009] Preferably, the product is used to extend healthy life span.

[0010] Preferably, the product is used to regulate metabolic status.

[0011] Preferably, the metabolite is ergosterol acetate.

[0012] Preferably, the product is one of fermented food, health food, daily chemical products, feed additives, probiotic preparations, and medicines.

[0013] Compared with the prior art, the present invention has the following beneficial effects:

[0014] (1) Prolonging healthy lifespan: The selected brewer’s yeast can significantly prolong the healthy lifespan of Drosophila melanogaster. Some strains have a significant effect on prolonging the lifespan of both female and male fruit flies.

[0015] (2) Improve physiological functions: The selected brewer’s yeast can not only prolong lifespan, but also improve the body’s motor ability.

[0016] (3) Improve intestinal barrier function: It improves the intestinal barrier function of elderly fruit flies and can alleviate age-related intestinal leakage problems.

[0017] (4) Regulating metabolic state: Reshaping the metabolic state of the fruit fly intestine, making the intestinal metabolism of old fruit flies closer to that of young fruit flies, and also affecting the protein abundance of extra-intestinal tissues. Most differentially expressed proteins are upregulated in fruit flies fed with brewer's yeast. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1This is a schematic diagram of the application effect process of an embodiment of the present invention;

[0019] Figure 2 Schematic diagram of the effect of Saccharomyces cerevisiae gene mutation on the health and lifespan of Drosophila, where (A) is the effect of the mutant strain on the host lifespan, (B) is the relationship between the change in host lifespan and its sleep duration, (C) is the correlation between sleep time and lifespan, (D) is the relationship between the change in host lifespan and its sleep fragments, and (E) is the relationship between the change in host lifespan and its climbing ability;

[0020] Figure 3 Schematic diagram of the anti-aging effect of anti-aging mutant strains, wherein (A) is the effect of 14 mutant strains on the lifespan of male fruit flies, (B) is the effect of 14 mutant strains on the lifespan of female fruit flies, (C) is the effect of 14 mutant strains on the climbing ability of fruit flies in middle age, (D) is the effect of 14 mutant strains on the climbing ability of fruit flies in young age, and (E) is the effect of 14 mutant strains on the sleep state of fruit flies in old age;

[0021] Figure 4 Schematic diagram of the effect of anti-aging mutant strains on the intestinal tract of Drosophila; (A) is a schematic diagram of the phenomenon of intestinal leakage in Drosophila, and (B) is a statistical diagram of the number of intestinal leaks in Drosophila in old age after being fed with different mutant strains;

[0022] Figure 5 Schematic diagram of the effect of anti-aging mutant bacteria on intestinal metabolism of Drosophila, where (A) is a diagram of the functional enrichment of mutant genes of 14 anti-aging mutant yeasts, (B) is a diagram of the significantly changed pathways in the intestine of long-lived Drosophila fed with mutant strains and a chord diagram on the right, (C) is a diagram of the modules determined by WGCNA, (D) is a schematic diagram of the correlation between modules and phenotypes, (E) is a diagram of metabolite enrichment results in blue and green modules, (F) is a heat map of terpenoid expression in anti-aging Drosophila, and (G) is a schematic diagram of the expression of ergosterol acetate in Drosophila fed with mutants;

[0023] Figure 6 Schematic diagram of the effects of anti-aging mutant bacteria on non-intestinal tissues of Drosophila. DETAILED DESCRIPTION

[0024] The present invention is further described in detail below in conjunction with specific embodiments.

[0025] Unless otherwise specified, the materials and reagents used in the following examples are commercially available.

[0026] Example

[0027] This example uses Drosophila melanogaster, a common model for aging research, to screen for Saccharomyces cerevisiae mutants that extend lifespan and improve the motor ability of aged Drosophila from a library of 2,600 single-gene mutant strains of Saccharomyces cerevisiae; and measures the metabolomics and proteomics of the intestinal and extraintestinal tissues of Drosophila to explore the anti-aging mechanism. Figure 1 As shown, the details are as follows:

[0028] 1. Experimental process

[0029] 1. Main reagent formula

[0030] (1) Methyl p-hydroxybenzoate solvent: 0.8 g of methyl p-hydroxybenzoate was dissolved in 4 mL of anhydrous ethanol.

[0031] (2) 0.6% sodium hypochlorite solution: 0.6 g sodium hypochlorite was dissolved in 100 mL sterile water.

[0032] (3) Saccharomyces cerevisiae culture medium (YPD medium): dissolve 10 g yeast extract, 20 g peptone, and 20 g glucose in 1 L deionized water and sterilize by high pressure for 30 min. For solid YPD, add 20 g agar powder to the above.

[0033] (4) Brilliant blue dye solution: 2.5 g of 85% brilliant blue powder was mixed into 100 mL of basic Drosophila culture medium.

[0034] (5) DAPI staining solution: 5 mg / mL DAPI ready-to-use solution was diluted with water at a ratio of 1:1000 to obtain 5 μg / mL DAPI staining solution.

[0035] (6) PBST solution: 1xPBS plus 0.1% Triton-X100.

[0036] 2. Cultivation of Drosophila

[0037] (1) Preparation of basic Drosophila culture medium

[0038] 1) Mix 350 ml of deionized water, 16 g of corn flour and 16 g of soybean flour, and boil to obtain a corn-soy flour mixture for later use. 2) Bring 350 ml of deionized water, 12 g of agar and 16 g of yeast extract (CAS number 8013-01-2) to a boil and then slowly add the corn-soy flour mixture.

[0039] 3) Add methyl paraben solvent and continue boiling for 3 minutes.

[0040] 4) Pour the above solution into a bottle and sterilize at 121°C for 20 minutes.

[0041] 5) Pour 100 ml of deionized water, 24 g of sucrose, and 12 g of glucose into another bottle and sterilize.

[0042] 6) After sterilization, mix in a clean bench and add 4 mL of propionic acid and mix well.

[0043] 7) After the bottles have cooled, plug them and place them in a 4°C refrigerator for later use.

[0044] (2) Preparation of Drosophila culture medium for experiments

[0045] On the basis of step 2), the yeast extract was removed and the remaining steps were kept consistent with the above “(1) Preparation of basal Drosophila culture medium”.

[0046] (3) Drosophila synchronization

[0047] Transfer young and energetic wild-type Drosophila melanogaster (WT) to a bottle containing a basic Drosophila culture medium and adapt for 1-2 days as spare Drosophila. Transfer the male and female Drosophila in the spare bottle to a wide-mouth bottle containing a basic Drosophila culture medium. Collect the Drosophila eggs after 6-8 hours and put them in a 25°C incubator for hatching. Feed them with yeast powder (i.e. Angel yeast powder sold in the market) to supplement nutrition during the 2nd to 5th day of Drosophila larvae. After about 10 days, a large number of Drosophila born at the same time can be hatched.

[0048] (4) Determining the sex of fruit flies

[0049] Take the fruit flies on the first day of eclosion after synchronization and place them on a fly sorting plate (fruit fly flight plate). Anesthetize the fruit flies by passing CO2, and use a fly sorting pen under a stereo microscope to pick out male or female fruit flies. Male fruit flies are smaller than female fruit flies, and the three black stripes behind their tails are connected into one piece. Male fruit flies have a pair of umbrella-shaped genitals at the end of their abdomen, while female fruit flies have a pair of reproductive tract openings. Most importantly, male fruit flies have sexual sparseness while females do not. Confirm the sex of the fruit flies based on these phenotypes. Ensure that the fly sorting equipment is relatively clean. Wipe it with 75% ethanol before and after each use, and sterilize it by high pressure once a week.

[0050] (5) Cultivation of sterile fruit flies

[0051] 1) Synchronize the flies in the jars according to the normal synchronization procedure and then transfer out the adult flies.

[0052] 2) Add double distilled water to rinse, gently brush off the eggs with a brush, and use a pipette to transfer the eggs into a centrifuge tube.

[0053] 3) Rinse with 0.6% sodium hypochlorite 5 times, disinfect with 75% ethanol 2 times, and clean with double distilled water 3 times.

[0054] 4) Transfer the eggs into new experimental culture medium and place them in a 25°C incubator to wait for them to emerge as adults.

[0055] 3. Cultivation of strains

[0056] (1) Strain recovery

[0057] 1) Take out some yeast mutants (i.e. selected from the single gene mutant strain library of Saccharomyces cerevisiae) from the -80 degree refrigerator. In the clean bench, use a pipette to take a certain amount of bacterial liquid ice crystals and add 1mL YPD culture base to the EP tube, mix, mark, and place in a shaker at 200rpm and 30℃ for one night.

[0058] 2) On the second day, remove the EP tube from the shaker, take a portion of the bacterial solution and place it on a slide, and observe under a microscope to see if there is any contamination; transfer the uncontaminated bacterial solution to a centrifuge tube containing 35 mL of YPD culture medium and place it in a shaker for shaking culture overnight.

[0059] 3) On the second day, take out the centrifuge tube, centrifuge at 7000 r / min for 5 min, then remove the centrifuge tube and discard the supernatant for later use.

[0060] (2) Bacteria spotting

[0061] Take several tubes of revived yeast and dilute them with 400 μL sterile PBS buffer. Use a pipette to transfer 200 μL of suspension drops into the fruit fly tubes containing fruit fly experimental culture medium, four tubes in a group. After the bacterial solution solidifies, plug it with cotton plugs and refrigerate for later use. The above operations are performed on a clean bench.

[0062] 4. Saccharomyces cerevisiae colonization detection

[0063] Method 1: Place the fruit flies to be tested on a fly sorting plate and anesthetize them with CO2, then rinse them with double distilled water 2-3 times, 2-3 minutes each time, and place them on a culture dish containing YPD solid culture medium. Use sterilized tweezers to hold the chest of the fruit fly with one end and the tail of the fruit fly with the other end, pull the two ends of the fruit fly to expose the intestine to YPD, or cut out the intestine and place it on YPD, then place it in a 30℃ incubator for culture, and observe whether there are white Saccharomyces cerevisiae colonies growing in the intestine after about 48 hours.

[0064] Method 2: Feed the fruit flies with food mixed with brilliant blue dye, and observe the intestinal tract under a stereo microscope 9 hours after feeding to see if there is blue.

[0065] 5. Drosophila lifespan experiment

[0066] The one-day-old male fruit flies to be tested were transferred into the fruit fly tubes containing the experiments after inoculation, with four tubes in each group and 20 flies in each tube. The tubes were marked with the date and strain, and stored in an incubator at 25°C. The culture medium and strain were replaced every 5-7 days, and the number of fruit flies that died in each group was recorded at a fixed time every day until all the fruit flies died. The survival indicators were recorded: the average number of days that all the fruit flies in each group survived was the average lifespan of the group; based on the data obtained, a survival curve was constructed to observe the effects of different mutant strains of brewer's yeast on the survival rate of fruit flies. The algorithm for the average lifespan of fruit flies is as follows: let the number of days that the fruit flies survive be d, and the number of fruit flies that died on the same day be xd. Then the average lifespan of fruit flies in each tube is

[0067] L=∑d*xd / 20

[0068] All data of repeated life span experiments were expressed as Mean ± SEM, and independent sample t-test was used to compare the experimental group and the control group, with P < 0.05 as statistically significant.

[0069] 6. Fruit fly climbing experiment

[0070] In each experiment, a camera was used to record the climbing process of fruit flies for observation. The day when fruit flies were transferred to the experimental tube was recorded as day 1. At 18:00 every day, the experimental tubes of day 10 and day 15 were taken horizontally and inverted. The fruit flies were gently shaken to the bottom of the experimental tube with the same force. The number of fruit flies that reached the top of the experimental tube within 10 seconds was tested, and the climbing index was calculated (the number of fruit flies that reached the top of the experimental tube within 10 seconds / the total number of surviving fruit flies in the tube). Each tube of fruit flies was tested at least 3 times, with at least 1 minute interval between each test. The average climbing index of each tube was recorded for each group.

[0071] 7. Drosophila sleep experiment

[0072] The DAM2 system is used to monitor the night sleep of the fruit flies. Specifically, each fruit fly is placed in a small tube that only allows it to pass through. The middle of the tube can be sensed by infrared. The system is used for continuous monitoring for 24 hours, and the night sleep time is defined as 0-8 o'clock. The static state of more than five consecutive minutes is defined as sleep (that is, the infrared does not sense the fruit fly passing for 5 consecutive minutes), the night sleep duration is the time of all static states, the sleep fragments are the number of times they wake up at night, and the number of movements is the number of times infrared senses the passing.

[0073] 8. Drosophila intestinal barrier integrity experiment

[0074] Add brilliant blue dye to fruit fly food, transfer the fruit flies to be tested to the culture medium containing brilliant blue dye, and observe the blue color in the fruit flies under a stereo microscope after 9 hours.

[0075] 9. Non-targeted metabolomics sequencing preprocessing and analysis

[0076] Take all 15 groups of fruit flies of two age groups to be tested, a total of 30 groups, each group with at least 10 fruit flies as a sample, 5 sample replicates for the young group, and 3 sample replicates for the old group (due to the fragility of the intestines in the elderly, the dissection is difficult, and the sample size is too large and the intestinal tissue is too small, so the number of replicates is reduced as appropriate). Quickly dissect the intestines of these fruit flies on ice, then put them into sample tubes with methanol as the solvent, and freeze them at -80. After all fruit flies are dissected, send them for testing.

[0077] The returned initial data was first processed using MSDIAL, and the annotation library was public. After quality control calibration, the peak area expression matrix was output as the expression data. Unknown metabolites that could not be identified were removed, and the duplicate metabolites were selected by selecting the one with the largest average intensity as the best. After manual screening, the expression results were output, and the result files were imported into R for preprocessing. The metabolite expression was quantile standardized, and the MetaboAnalystR package was used for differential analysis and other processing. In addition, WGCNA was used to identify metabolite sets with high synergistic changes.

[0078] 10. Proteome Sequencing of Drosophila Non-Intestinal Tissues

[0079] The samples were selected from the non-intestinal tissues of young flies used for the above-mentioned metabolomics sequencing. The protein profiles obtained by mass spectrometry were used for differential expression analysis of proteomic data using R language, combined with bioinformatics algorithms such as t-test, DESeq2, etc., to identify differentially expressed proteins.

[0080] The analysis results are presented through visualization tools such as bubble charts and heat maps, which clearly show the relative expression level of each protein and its association with biological function.

[0081] 11. Enrichment analysis and network diagram drawing

[0082] MetaboAnalyst was used to perform KEGG pathway enrichment analysis of differential metabolites. The analysis results were processed by R language. The GO (including biological process BP, cellular component CC, molecular function MF) and KEGG enrichment analysis of proteins were generated by DAVID website (https: / / david.ncifcrf.gov / home.jsp) and the analysis results were also processed by R language.

[0083] The protein-protein interaction network diagram was constructed using the STRING database, and the Cytoscape software was used for graphical processing and display. The FlyScape plug-in in Cytoscape was used to construct a Drosophila metabolite network diagram to show the relationships between Drosophila metabolites.

[0084] 12. Data statistics and analysis

[0085] The experimental data were analyzed using GraphPad Prism 8 software. The experimental results were expressed as "Mean ± SEM or SD" (SD was used for the mean within the group, and SEM was used for the mean between groups). The significance of the difference between the groups was analyzed using the Unpaired t test. If the variance was not uniform, a non-parametric test method was used. The significance level was P < 0.05 (*).

[0086] 2. Experimental Results Analysis

[0087] 1. Detecting the effects of Saccharomyces cerevisiae gene mutations on the health and lifespan of Drosophila

[0088] Male Drosophila melanogaster was used as an animal model, and 1,600 strains of single-gene knockout Saccharomyces cerevisiae were used as research subjects. The three health-related indicators of Drosophila, lifespan, sleep and climbing, were tested, and the correlation between the indicators was analyzed.

[0089] The study found that compared with the wild-type control BY4743 strain, the health status of fruit flies fed with different single-gene knockout yeast strains changed significantly, among which about 17% of the Saccharomyces cerevisiae mutants could significantly extend the lifespan of fruit flies by more than 10% (P<0.05) ( Figure 2 A); the change in host lifespan may be slightly positively correlated with its sleep duration (P = 0.08) ( Figure 2 B), the life span of fruit flies whose sleep time was reduced by more than 10% was significantly shortened (P<0.05) ( Figure 2 C); There was no significant correlation between the lifespan and sleep fragmentation or motor ability of flies fed different mutant strains ( Figure 2 D and Figure 2 E).

[0090] 2. Confirm the significant anti-aging mutant strains and verify the anti-aging effects of the anti-aging mutant strains

[0091] The strains obtained by high-throughput screening were subjected to repeated lifespan experiments to confirm the significantly anti-aging mutant strains (P<0.05), and various health indicators such as lifespan, motor ability, sleep fragments and number of nocturnal activities were further tested in male fruit flies, as well as the effect on the lifespan of female fruit flies.

[0092] It was found that 14 mutant strains significantly increased the lifespan of fruit flies: after multiple repeated experiments, it was confirmed that compared with wild-type control fruit flies, 14 mutant strains could significantly extend the lifespan of male fruit flies (P<0.05) ( Figure 3 A), the average lifespan of the host was increased by 13.65%, with the highest extension of 18%; 10 of the strains also significantly extended the lifespan of female fruit flies (P<0.05) ( Figure 3B); Among the 14 strains that extend the lifespan of male fruit flies, 13 strains can significantly improve the host's climbing ability in middle age (P<0.05) ( Figure 3 C), and 5 of them can also significantly improve the host's climbing ability in youth ( Figure 3 D); The sleep quality of old fruit flies fed with anti-aging mutant bacteria improved to a certain extent, but there was no significant difference ( Figure 3 E).

[0093] 3. Detecting the effects of anti-aging mutant strains on the intestinal tract of Drosophila

[0094] The "Smurf" experiment was used to detect intestinal leakage in aged Drosophila and to evaluate the effects of anti-aging mutant strains on the host intestinal barrier function.

[0095] Anti-aging mutant bacteria can improve the intestinal leakage of old fruit flies: the proportion of intestinal leakage in the middle and late-life fruit flies fed with wild-type strains was 11.63%, while the intestinal leakage in the late-life fruit flies fed with mutant strains was reduced to below 7.14 (P<0.05) ( Figure 4 A and 4B).

[0096] 4. Exploring the effects of anti-aging mutant bacteria on intestinal metabolism in Drosophila

[0097] Non-targeted metabolomics detected the metabolic changes in the intestines of fruit flies fed with anti-aging mutant strains at two age groups, determined the differential metabolites in the intestinal tissues of each fruit fly fed with anti-aging mutant strains, and further used enrichment analysis (EA) and weighted gene co-expression network analysis (WGCNA) to screen differential metabolites and anti-aging candidate pathways.

[0098] Anti-aging mutant yeast strains improve metabolism in the intestines of aged fruit flies: The functions of mutant genes in 14 anti-aging mutant yeasts are closely related to metabolic processes ( Figure 5 A); Non-targeted metabolomics of the Drosophila intestine showed that compared with the wild control Saccharomyces cerevisiae strain BY4743, the arginine biosynthesis pathway, purine metabolism pathway and riboflavin metabolism pathway in the intestine of long-lived Drosophila fed with mutant strains were significantly changed, and they were listed as candidate anti-aging pathways ( Figure 5 B). WGCNA identified five modules, as well as the correlations between modules and with phenotypes ( Figure 5 CD). Among these modules, except for the brown and yellow modules with low enrichment in the pathway, the green and blue modules have a strong relationship with the mutant strain phenotype. The enrichment results show that the metabolites in the blue module are mainly related to sphingolipid metabolism and unsaturated fatty acid biosynthesis, and the green module is mainly related to arginine biosynthesis ( Figure 5 E), which suggests that the effect of the mutant strain on the host is related to this. In addition, this example also found that in the anti-aging mutant, terpenoids were significantly overexpressed ( Figure 5F), after screening, ergosterol acetate was confirmed as an anti-aging candidate substance, which was significantly upregulated in long-lived Drosophila ( Figure 5 G).

[0099] 5. Explore the effects of anti-aging mutant bacteria on non-intestinal tissues of Drosophila:

[0100] By performing proteomic sequencing on non-intestinal tissues of fruit flies fed with mutant strains, we studied whether the metabolic reprogramming caused by the mutant strain had an impact on the host system.

[0101] The results showed that the intestinal mutant bacteria not only rebuilt host metabolism in the intestinal tissue, but also affected the protein level throughout the body. A total of 3063 proteins were detected in the tissues of wild-type fruit flies, while 3390 proteins were detected in the tissues of fruit flies fed with mutant bacteria, of which 387 unique proteins were enriched in cellular metabolism and energy regulation, especially mitochondrial function pathways. These processes affect energy metabolism and intracellular signal transduction, indicating that there may be a potential mechanism for regulating lifespan through protein phosphorylation and the establishment or maintenance of cell polarity ( Figure 6 ).

Claims

1. Use of Saccharomyces cerevisiae and its metabolites in the preparation of anti-aging products, wherein the Saccharomyces cerevisiae is screened from a Saccharomyces cerevisiae gene knockout strain library, and the Saccharomyces cerevisiae lacks any one of the genes YJR044C, YDR176W, YPL257W, YCL051W, YAL053W, YAL044C, YER164W, YPL253C, YER169W, YBR041W, YNL125C, YER174C, YML088W, and YLL015W; the nucleotide sequences of YJR044C, YDR176W, YPL257W, YCL051W, YAL053W, YAL044C, YER164W, YPL253C, YER169W, YBR041W, YNL125C, YER174C, YML088W, and YLL015W are as shown in SEQ As shown in ID NO.1-14.

2. The use of the brewer's yeast and its metabolites in the preparation of anti-aging products according to claim 1, characterized in that: The product is used to improve athletic performance.

3. The use of the brewer's yeast and its metabolites in the preparation of anti-aging products according to claim 1, characterized in that: The product is used to improve the integrity of the intestinal barrier.

4. The use of the saccharomyces cerevisiae and its metabolites in the preparation of anti-aging products according to claim 1, characterized in that: The product is used to extend healthy life span.

5. The use of the saccharomyces cerevisiae and its metabolites in the preparation of anti-aging products according to claim 1, characterized in that: The products are used to regulate metabolic status.

6. The use of the saccharomyces cerevisiae and its metabolites in the preparation of anti-aging products according to claim 1, characterized in that: The metabolite is ergosterol acetate.

7. The use of the saccharomyces cerevisiae and its metabolites in the preparation of anti-aging products according to claim 1 or 2, characterized in that: The product is one of fermented food, health food, daily chemical products, feed additives, probiotic preparations and medicines.

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