Decomposition accelerators for enhanced recycling

Abstract

The present invention provides a new formulation for enhancing the recycling of cells, etc., and a method for increasing various related gene responses for enhancing the recycling of cells, etc. [Solution] A decomposition system promoter for promoting recycling containing a water-soluble nuclear protein, in particular a water-soluble nuclear protein which is a low molecular weight substance having a molecular weight of 250 to 15,000 obtained by enzymatically treating fish milt, a health food containing said decomposition system promoter, and a method for increasing the response of various decomposition system-related genes and a method for promoting recycling of cells, etc. by orally ingesting said decomposition system promoter.

Description

[Technical field]

[0001] The present invention relates to a decomposition system involved in promoting the recycling of cells, etc., and more particularly to a decomposition system promoter that promotes decomposition systems such as proteasomes, autophagy, and apoptosis, thereby promoting the recycling of cells, organelles, etc. The present invention also relates to a method for increasing the response of various degradation-related genes (proteasome-related genes, autophagy-related genes, apoptosis-related genes) by orally ingesting the degradation-related promoter. [Background technology]

[0002] In recent years, reflecting the growing public interest in health, health foods have been provided that use deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and nucleoprotein (also called salmon milt extract), a complex of these nucleic acids and proteins, as raw materials or active ingredients. For example, nucleoprotein is known to have immunomodulatory, antioxidant, vasodilatory, and other effects. In addition, there has been a proposal for a cancer cell proliferation inhibitor that contains low-molecular-weight water-soluble nucleic acid, or the water-soluble nucleic acid and amino acid (Patent Document 1). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] JP 2014-152144 A Summary of the Invention [Problem to be solved by the invention]

[0004] It has been reported that the ingestion of nucleic acids (DNA, RNA) and nuclear proteins produces a variety of actions and effects, including antioxidant effects. However, there have been no reports to date that the intake of these substances affects the breakdown of aged cells or unnecessary oxidized proteins or damaged mitochondria within cells, thereby affecting the recycling of the cells themselves or their organelles. Now, as degradation systems for recycling in cells, there is the ubiquitin-proteasome system, which selectively degrades unnecessary or damaged proteins in the cell, and autophagy, which is associated with autophagosome vesicles involved in the self-degradation of damaged or dysfunctional organelles in the cell. In addition, the selective removal of damaged mitochondria is called mitophagy. Autophagy is "non-selective" in its targets for degradation, whereas the aforementioned ubiquitin-proteasome system selectively degrades proteins by marking them with ubiquitin proteins. Recent studies have reported that these phenomena are related to aging and disease. For example, in Drosophila, it has been reported that mutations in autophagy system genes reduce the average lifespan, while overexpression increases the average lifespan. In addition, a relationship between autophagy and neurodegenerative diseases such as Alzheimer's dementia and Parkinson's disease has been recognized, and it has been reported that autophagy failure causes the accumulation of amyloid proteins such as β-amyloid and α-synuclein. However, there have been no reports to date that the ubiquitin-proteasome system or autophagy is related to antioxidant activity.

[0005] An objective of the present invention is to provide a new preparation for enhancing the recycling of cells, etc., and a method for increasing the response of various genes related to the enhancement of the recycling of cells, etc. [Means for solving the problem]

[0006] The present invention relates to a degradation system promoter containing a water-soluble nuclear protein for promoting recycling, in particular to a degradation system promoter containing a nuclear protein obtained by enzymatically treating fish milt and degraded to a molecular weight of 250 to 15,000.The present invention particularly relates to a degradation system promoter targeting the proteasome degradation system, the autophagy degradation system, or apoptosis. The present invention also relates to health foods containing the decomposition promoter, for example health foods in the form of tablets, drinks, capsules, granules, powders, pills or jellies. The present invention further relates to a method for increasing the response of proteasome-related genes, a method for increasing the response of autophagy-related genes, or a method for increasing the response of apoptosis-related genes by orally ingesting the degradation system promoter, and also to a method for enhancing the recycling of cells, organelles, or proteins by orally ingesting the degradation system promoter.

[0007] The present invention also covers agents that increase the response of proteasome-related genes, autophagy-related gene responses, and apoptosis-related gene responses, as well as agents that enhance the recycling of cells, organelles, or proteins, all of which contain water-soluble nuclear proteins. Effect of the Invention

[0008] The decomposition system promoter of the present invention, which contains a water-soluble nuclear protein, particularly a nuclear protein degraded by enzymatically treating fish milt, promotes proteasome activation, autophagy activation, and apoptosis activation by orally ingesting the promoter, thereby promoting the decomposition and removal of oxidized proteins and organelles such as defective mitochondria, and further promoting cell death itself, thereby achieving the effect of promoting the recycling of these cells, etc. Furthermore, the promotion of the recycling promotion effect is expected to contribute to health maintenance, such as antioxidation and disease prevention. [Brief description of the drawings]

[0009] [Figure 1]Figure 1 shows the results of d-ROMs tests performed on the blood of subjects before and after intake of test tablets containing water-soluble nuclear protein (salmon milt extract) for 8 weeks in the test tablet group, and placebo tablets not containing the extract for 8 weeks in the placebo tablet group. (A) Time course of d-ROMs (measured value); B) Amount of change in d-ROMs (amount of change relative to pre-ingestion levels). [Diagram 2] FIG. 2 shows the results of comprehensive gene expression analysis by microarray using total RNA extracted from human blood in human subjects after ingesting water-soluble nuclear protein (salmon milt extract) for 8 weeks. [Diagram 3] FIG. 3 shows the yeast that survived in hydrogen peroxide after 72 hours of culture at 30° C. in a test group in which a water-soluble nuclear protein (salmon milt extract) was added at 1% to a culture medium in which yeast (Saccharomyces cerevisiae (BY4741 strain) was cultured in SD complete liquid medium) was grown, and in a control group in which only a culture medium in which yeast (Saccharomyces cerevisiae (BY4741 strain) was grown in SD complete liquid medium) was grown. The culture medium after 24 hours of treatment was appropriately diluted and plated on a YPD plate medium supplemented with 4 mM hydrogen peroxide. [Figure 4] FIG. 4 shows the survival rates calculated for a test group in which a water-soluble nuclear protein (salmon milt extract) was added at 1% to a culture medium in which yeast (Saccharomyces cerevisiae (BY4741 strain)) was cultured in SD complete liquid medium, and for a control group in which only a culture medium in which yeast (Saccharomyces cerevisiae (BY4741 strain)) was cultured in SD complete liquid medium was added. The culture medium after 24 hours of treatment was appropriately diluted and plated on YPD plate media supplemented with 4 mM hydrogen peroxide and on YPD plate media without hydrogen peroxide, and the number of surviving colonies (number of colonies) was counted with and without the addition of hydrogen peroxide after 72 hours of culture at 30°C. [Diagram 5]FIG. 5 shows the results of comprehensive gene expression analysis using a microarray of total RNA extracted from yeast (Saccharomyces cerevisiae ((BY4741 strain)) 24 hours after adding a water-soluble nuclear protein (salmon milt extract) to the yeast. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The degradation system promoter of the present invention contains a water-soluble nuclear protein. The present inventors have newly confirmed that the water-soluble nuclear protein activates proteasomes, autophagy, and apoptosis, which are the degradation systems of intracellular components and cells themselves, that is, promotes the degradation and removal of defective proteins and defective organelles such as oxidized proteins, carbonylated proteins, defective mitochondria, and damaged lysosomes, and further promotes cell death itself. Therefore, the degradation system promoter of the present invention is expected to remove the defective proteins, defective cells, cell organelles, etc., and contribute to the recycling of these cells, etc., by orally ingesting it into the body. The present invention will be described in detail below.

[0011] In the degradation system promoter of the present invention, the degradation systems to be targeted are the proteasome degradation system, the autophagy degradation system, and apoptosis. These can be said to be different in the scale of degradation systems, so to speak, with proteasomes being related to the selective degradation of defective proteins, autophagy being related to the degradation of defective proteins and defective intracellular organelles in the cytoplasm, and apoptosis being related to the degradation of the cells themselves (cell death). By promoting the degradation of these defective cells and making them into a form that is easy to recycle into new cells, it can lead to the promotion of recycling of cells, etc. Furthermore, as mentioned above, the proteasome system and autophagy are involved in aging and various diseases, and mutations and decreases in these degradation systems lead to undesirable phenomena such as shortened lifespan, so it is believed that the promotion of autophagy and the proteasome system by the intake of nucleic acids (DNA, RNA) and nuclear proteins can be expected to have anti-aging and health maintenance, in addition to simply improving the antioxidant effect by the intake of nucleic acids.

[0012] The water-soluble nuclear protein used in the degradation promoter of the present invention, the proteasome-related gene response enhancer, the autophagy-related gene response enhancer, the apoptosis-related gene response enhancer, and the cell, organelle, or protein recycling enhancer described below, can be a water-soluble nuclear protein obtained by extracting nucleic acid from a biological cell and reducing its molecular weight by enzymatic treatment. In other words, the water-soluble nuclear protein in this specification can be rephrased as a reduced molecular weight extract of fish milt. One example of the water-soluble nuclear protein is a water-soluble nuclear protein obtained by reducing the molecular weight of fish milt by enzymatic treatment or the like to make it water-soluble (e.g., salmon milt extract). In this specification, water-soluble refers to the property of being soluble in water at a concentration of 0.1% by mass or more.

[0013] Examples of the fish include salmon, trout, herring, etc. Among these, salmon milt, which contains a lot of nucleic acids but has not been effectively utilized as a resource in the past and has been largely discarded, can be preferably used.

[0014] An example of an enzymatic treatment of fish milt is a method in which a suspension obtained by crushing fish milt is treated with a protease and then with a nuclease. Usually, when DNA or the like is extracted from milt, the molecular weight is 1,000,000 or more, and this is reduced in molecular weight by enzymatic treatment. Preferred water-soluble nuclear proteins include those that contain preferably 20% by mass or more, more preferably 30% by mass or more of nucleosides / nucleotides / oligonucleotides / polynucleotides (hereinafter also referred to as reduced molecular weight products) having a molecular weight of 250 to 100,000, for example, a molecular weight of 250 to 20,000, a molecular weight of 250 to 15,000, a molecular weight of 500 to 13,200, a molecular weight of 250 to 10,000, or a molecular weight of 250 to 6,600. More preferably, the water-soluble nuclear protein of the present invention (e.g., salmon milt extract) can contain 2% by mass or more of low molecular weight substances having a molecular weight of 500 to 15,000 and 18% by mass or more of low molecular weight substances having a molecular weight of 250 to 6,600.

[0015] Examples of the protease include serine protease, cysteine ​​protease, metalloprotease, and aspartic acid protease. Since fish milt contains proteins other than protamine, a protease with low substrate specificity is particularly preferred. An example of a good protease is a protease manufactured by Novozymes Japan Co., Ltd. The hydrolysis treatment using the protease can be carried out at a temperature in the range of 30 to 60°C, for example, in the range of 40 to 50°C, and at a pH in the range of 6 to 7, taking into consideration the activation and inactivation of the protease. The nuclease hydrolyzes the 3,5'-phosphodiester bond of deoxyribonucleic acid (DNA) to generate 5'-nucleotides for oligomerization. There are no particular limitations on the properties of the nuclease, but it is preferable that the nuclease has a certain degree of thermal stability. Such nucleases are commercially available from, for example, Amano Enzyme Inc. and Sigma. The hydrolysis treatment using the nuclease can be carried out, for example, at a temperature in the range of 60 to 75°C and a pH in the range of 5 to 6, taking into account the activation and inactivation of the nuclease. Specifically, the enzymatic treatment procedure involves first treating milt (e.g., salmon milt) with a protease to hydrolyze proteins and the like contained in the milt, and then, after completion of hydrolysis, treating with a nuclease to break down nucleic acids into smaller molecules.

[0016] The present invention also relates to a health food containing the decomposition system promoter. The health food of the present invention contains as an active ingredient the decomposition promoter, for example, a water-soluble nucleoprotein, which is a low molecular weight product with a molecular weight of 250 to 15,000, for example, about 250 to 10,000 obtained by enzymatically treating fish milt, and contains other ingredients according to the various product forms described below. The content of the recycling agent in the health food can be appropriately adjusted with reference to the clinical dosage described below.

[0017] The health food of the present invention can be mixed with various known ingredients such as sweeteners, acidulants, vitamins, etc. to produce a product that meets the tastes of the user. The product form can be, for example, tablets, capsules, granules, powders, pills, syrups, liquids, emulsions, suspensions, etc., or drinks, jellies, dairy products such as yogurt, seasonings, processed foods, desserts, confectioneries, etc.

[0018] For example, the tablets, capsules, granules, powders, pills and the like for oral administration can be formulated by conventional means, and these are prepared using excipients such as sucrose, lactose, glucose, starch, mannitol; binders such as hydroxypropylcellulose, syrup, gum arabic, gelatin, sorbitol, tragacanth, methylcellulose, polyvinylpyrrolidone; disintegrants such as starch, carboxymethylcellulose or a calcium salt thereof, microcrystalline cellulose, polyethylene glycol; lubricants such as talc, magnesium or calcium stearate, silica; and lubricants such as sodium laurate, glycerol and the like. The syrups, solutions, emulsions, suspensions, etc. can also be formulated by conventional means, and are prepared using a solvent for the decomposition system accelerator, which is the active ingredient, such as water, ethyl alcohol, isopropyl alcohol, propylene glycol, 1,3-butylene glycol, polyethylene glycol; surfactants, such as sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene ethers of hydrogenated castor oil, lecithin; suspending agents, such as cellulose derivatives such as carboxymethyl sodium salt, methylcellulose, natural gums such as tragacanth, gum arabic, etc.; and preservatives, such as esters of paraoxybenzoic acid, benzalkonium chloride, sorbic acid salts, etc. Furthermore, the above-mentioned drinks and jellies, as well as dairy products, seasonings, processed foods, desserts, sweets, etc., may contain, in addition to their constituent ingredients, oligo-RNA, zinc, collagen, chondroitin, hyaluronic acid, vitamins (B vitamins such as vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, etc.), glutathione (glutathione-containing yeast extract, reduced glutathione, oxidized glutathione, etc.). More specifically, for example, for drink applications, but not limited to this application, pig collagen peptide, rare sugar-containing syrup, RNA-containing edible yeast extract, zinc-containing edible yeast, chondroitin-containing shark cartilage extract, hyaluronic acid-containing cockscomb extract / acidulant, vitamin C, arginine, magnesium carbonate, niacin, vitamin B6, vitamin B2, vitamin B1, folic acid, vitamin B12, anserine-containing fish meat extract, citrulline, salmon ovarian membrane extract, pig placenta extract, etc. can be blended. For example, for tablet applications, but not limited to this application, brewer's yeast, ginkgo leaf extract, S-allyl cysteine-containing garlic extract, etc. can be blended. Furthermore, for example, for jelly applications, but not limited to this application, fish collagen peptide, etc. can be blended.

[0019] Furthermore, the health food of the present invention may contain, in addition to the decomposition promoter as an active ingredient, other medicamentously or veterinarily active compounds.

[0020] The clinical dosage of the decomposition promoter of the present invention varies depending on the age, body weight, patient sensitivity, severity of symptoms, etc., but the standard of the usually effective dosage is about 100 mg to 500 mg per day for an adult, for example, as the amount of water-soluble nuclear protein (salmon milt extract). However, an amount outside the above range can be used if necessary. The above-mentioned effective dosage guidelines also apply to the health food of the present invention. In the case of health food, for example, the amount of the decomposition promoter in the health food can be appropriately adjusted based on the daily intake of the health food itself, with reference to the above-mentioned daily dosage guidelines.

[0021] The decomposition system promoter of the present invention increases the response genes related to the above-mentioned decomposition systems, thereby promoting these decomposition systems. That is, the present invention also covers a method for increasing the response of proteasome-related genes, autophagy-related genes, and apoptosis-related genes by orally ingesting the decomposition promoter. Since the decomposition of cells and the like ultimately promotes recycling, the present invention also covers a method for promoting the recycling of cells, organelles, or proteins. In the methods for increasing the response of these genes and the methods for promoting recycling, the same clinical dosages (recommended dosages) as those of the decomposition promoter can be preferably applied as they are.

[0022] As described above, the present invention is directed to agents that enhance the response of proteasome-related genes, autophagy-related gene response, and apoptosis-related gene response, containing water-soluble nuclear proteins (e.g., salmon milt extract), and is also directed to agents that enhance the recycling of cells or organelles, and further to agents that enhance the recycling of cells, organelles, or proteins. As described above, these response enhancers and recycling enhancers contain water-soluble nuclear proteins (e.g., salmon milt extract), and the water-soluble nuclear proteins (e.g., salmon milt extract) used in the decomposition promoter described above can be preferably used. Furthermore, these response enhancers and recycling enhancers can be in the form of health foods that contain them. The health foods can preferably use the aspects and ingredients listed for the health foods that contain the decomposition accelerators described above. EXAMPLES

[0023] <Water-soluble nuclear protein (salmon milt extract)> Water-soluble nuclear protein (salmon milt extract) obtained from salmon milt using hydrolases such as proteases and nucleases contained 20 to 30% by mass of nucleic acids (water-soluble nucleic acids with molecular weights ranging from 250 to 15,000) and 50% by mass of amino acids (including 15% by mass of arginine).

[0024] <Production of test tablets> According to Table 1, a test tablet (tablet A) containing the water-soluble nucleoprotein (salmon milt extract) obtained in the above Preparation Example and a placebo tablet (tablet B) not containing the extract were prepared.

[0025] [Table 1]

[0026] <Test Example (1): Changes in oxidative stress markers> A double-blind, randomized, placebo-controlled study was conducted on 41 healthy subjects aged 40 to 60 years (male, not taking any medication, and with no underlying diseases). The subjects were divided into two groups, a test tablet group (tablet A, 20 subjects) and a placebo tablet group (tablet B, 21 subjects), and each test group was administered either tablet A or tablet B for 8 weeks. The test tablet group was administered a quantity of tablet A adjusted so that the daily intake of water-soluble nuclear protein (salmon milt extract) was 360 mg (6 tablets per day), and the placebo tablet group was administered the same amount of tablet B as tablet A (6 tablets per day). Blood samples were taken from the subjects before and after intake (0 and 8 weeks) and the levels of hydroperoxides, which are metabolites of free radicals in the blood, were measured to conduct a d-ROMs (Reactive Oxygen Metabolites-derived compounds) test, which comprehensively evaluates the level of oxidative stress in the body. In addition, total RNA was extracted from the collected blood and subjected to gene expression analysis.

[0027] The results are shown in Figure 1 [results of the d-ROMs test (Figure 1 (A) measured values, (B) changes from values ​​before intake)]. As shown in Figure 1, the test tablet group that took tablet A, which contains water-soluble nuclear protein (salmon milt extract), for 8 weeks showed a significant decrease in the measured value and change in d-ROMs (reduction in oxidative stress markers) compared with the placebo tablet group.

[0028] <Test Example (2): Gene Expression Analysis> As in Test Example (1), subjects in two groups, a test tablet group (tablet A, 20 subjects) and a placebo tablet group (tablet B, 21 subjects), were given each tablet for 8 weeks. After that, total RNA was extracted from blood collected from the subjects, and comprehensive gene expression analysis was performed. The conditions for the comprehensive gene expression analysis are as follows: <Comprehensive gene expression analysis using microarrays> Microarray used: Thermofisher Applied Biosystems (registered trademark) Clariom S Array, Human 1. Total RNA quality check (assessment of RNA degradation) was performed using an Agilent 2100 Bioanalyzer (Agilent Technologies). 2. Samples with an RNA concentration of 100 ng / μl or more, an RNA amount of 300 ng or more, an A260 / 280 ratio of 1.8-2.1, and an RIN value of 7.0 or more were used in the test. 3. cRNA synthesis was performed using the GeneChip WT Plus Reagent Kit. Using 100 ng of total RNA as a template, the first cycle of first-strand cDNA was synthesized by reverse transcription, and then second-strand cDNA was synthesized. Next, cRNA was synthesized by in vitro transcription. After purification, the yield of cRNA was measured using a spectrophotometer. 4. Single-strand cDNA was synthesized from cRNA using the GeneChip WT Plus Reagent Kit. Second-cycle single-strand cDNA was synthesized from the first cRNA by reverse transcription. The synthesized single-stranded DNA was purified and the yield was measured using a spectrophotometer. 5. Single-stranded DNA was fragmented and labeled using the GeneChip WT Terminal Labeling Kit (Thermo Fisher Scientific). 5.5 μg of ssDNA was fragmented using uracil DNA glycosylase (UDG) and apurinic / apyrimidinic endonuclease 1 (APE1). The fragmented ssDNA was then biotinylated using terminal deoxynucleotidyl transferase (TdT) and GeneChip DNA Labeling Reagent. 6. Hybridization to Clariom S Array, Human was performed using the GeneChip Hybridization, Wash, and Stain Kit (Thermo Fisher Scientific). Fragmented and labeled ssDNA was added to the hybridization buffer and hybridized on Clariom S Array, Human for 17 hours. After washing and staining, the fluorescence was read using a scanner, and a CEL file was created using GCC (GeneChip Command Console Software), and the Expression Console was used to generate the CEL file. TM A CHP file was created using the software. 7. Transcriptome Analysis Console (Thermo Fisher Scientific) was used to evaluate the fold change of transcripts at ≥1.3 and to perform pathway analysis. The results of gene expression analysis related to various degradation systems (proteasome, autophagy, and apoptosis) are shown in Table 2. The results of comprehensive gene expression analysis in the proteasome degradation system and autophagy are shown in Figure 2.

[0029] [Table 2]

[0030] As shown in Table 2, it was confirmed that the test tablet group that took tablet A containing water-soluble nuclear protein (salmon milt extract) for 8 weeks significantly increased the expression of genes related to various decomposition systems compared to the placebo tablet group.

[0031] <Test Example (3) Evaluation of oxidative stress resistance using yeast> The yeast (Saccharomyces cerevisiae) used was prepared by isolating -80°C stock of the BY4741 strain on a plate, picking out 2-3 independent colonies, and culturing them in SD complete medium for 18 hours with shaking (160 rpm, 30°C) to increase the number of bacteria. A test group was prepared by adding 1 / 10 the amount of yeast culture solution and the above-mentioned water-soluble nuclear protein (salmon milt extract) to a new SD complete liquid medium at 1% of the medium, and a control group was prepared by adding only the above-mentioned yeast-added SD complete liquid medium (water-soluble nuclear protein (salmon milt extract)). Each was cultured for 24 hours. The yeast culture solution cultured for 24 hours was washed twice with sterile distilled water, and the water-soluble nuclear protein (salmon milt extract) was removed from the medium. The yeast culture solution was appropriately diluted so that independent colonies were obtained, and then inoculated on a YPD plate medium to which hydrogen peroxide was added at 4 mM. After culturing for 72 hours at 30°C, the number of yeast colonies that survived in the presence of hydrogen peroxide was counted. The appearance of the test group and the control group after 72 hours of culture is shown in Figure 3. As shown in FIG. 3, more colonies were confirmed in the test group to which water-soluble nuclear protein (salmon milt extract) was added, compared to the control group to which water-soluble nuclear protein (salmon milt extract) was not added.

[0032] In addition, similar to the hydrogen peroxide-added system described above, systems in which hydrogen peroxide was not added (no hydrogen peroxide added) [yeast + water-soluble nuclear protein (salmon milt extract) group, yeast only (no water-soluble nuclear protein (salmon milt extract) added) group] were also cultured at 30°C for 72 hours. The number of colonies growing on each medium was counted, and the yeast survival rate (%) was calculated by dividing the number of colonies on the medium with hydrogen peroxide by the number of colonies on the medium without hydrogen peroxide, with or without water-soluble nuclear protein (salmon milt extract). The results are shown in Figure 4. As shown in FIG. 4, the survival rate of the yeast to which water-soluble nuclear protein (salmon milt extract) was added was significantly higher than the survival rate of the yeast to which water-soluble nuclear protein (salmon milt extract) was not added.

[0033] <Test Example (4) Comprehensive gene expression analysis using yeast microarrays> The above-mentioned water-soluble nuclear protein (salmon milt extract) was added at 1% to yeast (Saccharomyces cerevisiae (BY4741 strain (MATa; his3D1; leu2D0; met15D0; ura3D0)), and after 24 hours, comprehensive gene expression analysis was performed using microarrays with total RNA extracted from the yeast. Microarray used: ThermoFisher Genechip Yeast Genome 2.0 Array 1.A quality check (concentration measurement) of total RNA was performed using an Agilent 2200 TapeStation. 2. Using 250 ng of total RNA each, a labeling reaction was carried out using the GeneChip (registered trademark) 3' IVT PLIS Kit, followed by hybridization. 3.Expression Console TM The signals were quantified using the RMA algorithm, and the quantified signal values ​​were normalized using the quantile method. 4. Transcriptome Analysis Console (Thermo Fisher Scientific) was used to evaluate the ratio of changes in transcripts to those of 1.3 or higher, and pathway analysis was performed. The results of gene expression analysis related to various degradation systems (proteasome, autophagy) are shown in Table 3 and Figure 5.

[0034] [Table 3]

[0035] As shown in Table 3, it was confirmed that the group in which water-soluble nuclear protein (salmon milt extract) was added to yeast and left for 24 hours had significantly increased expression of genes related to various decomposition systems compared to the placebo (no addition) group.

[0036] The results, which show that water-soluble nuclear protein (salmon milt extract) contributes to the reduction of oxidative stress markers and increases the expression levels of genes related to cell degradation systems, such as proteasomes, autophagy, and apoptosis, in both humans and yeast, suggest that nuclear protein can contribute to promoting the degradation of defective or damaged proteins, organelles such as mitochondria, and cells themselves, and that it may be involved in the recycling of these degraded cells to generate new cells, thereby potentially contributing to the reduction and suppression of oxidative stress and the promotion of health.

Claims

1. A decomposition system promoter for enhancing recycling, which contains a water-soluble nuclear protein having a molecular weight of 250 to 15,000 obtained by enzymatically treating fish milt.

2. The degradation system promoter according to claim 1 , wherein the degradation system is a proteasome degradation system.

3. The decomposition system promoter according to claim 1 , wherein the decomposition system is an autophagy decomposition system.

4. The decomposition system promoter according to claim 1 , wherein the decomposition system is apoptosis.

5. A health food for promoting the decomposition system for enhancing recycling, comprising the decomposition system promoter according to claim 1.

6. A health food for promoting the proteasome degradation system to enhance recycling, comprising the degradation system promoter according to claim 2.

7. A health food for promoting the autophagy decomposition system to enhance recycling, comprising the decomposition system promoter according to claim 3.

8. A health food for promoting apoptosis to enhance recycling, comprising the decomposition promoter according to claim 4.

9. The health food according to claim 5 , which is in the form of a tablet, a drink, a capsule, a granule, a powder, a pill or a jelly.

10. The health food according to claim 6, which is in the form of a tablet, a drink, a capsule, a granule, a powder, a pill or a jelly.

11. The health food according to claim 7, which is in the form of a tablet, a drink, a capsule, a granule, a powder, a pill or a jelly.

12. The health food according to claim 8, which is in the form of a tablet, a drink, a capsule, a granule, a powder, a pill or a jelly.

13. A response enhancer for proteasome-related genes, comprising a water-soluble nuclear protein having a molecular weight of 250 to 15,000 obtained by enzymatically treating fish milt.

14. An agent for increasing the response of autophagy-related genes, comprising a water-soluble nuclear protein having a molecular weight of 250 to 15,000 obtained by enzymatically treating fish milt.

15. An agent for increasing the response of apoptosis-related genes, comprising a water-soluble nuclear protein having a molecular weight of 250 to 15,000 obtained by enzymatically treating fish milt.

16. A recycling enhancer for cells, organelles or proteins, comprising a water-soluble nuclear protein having a molecular weight of 250 to 15,000 obtained by enzymatically treating fish milt.

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