Decomposition system promoter for promoting recycling

Abstract

[Problem] To provide: a novel formulation associated with the promotion of recycling cells or the like; and a method for increasing the responses of various related gene associated with the promotion of recycling of cells or the like. [Solution] Provided are: a decomposition system promoter for promoting recycling, the promoter containing a water-soluble nuclear protein, particularly a water-soluble nuclear protein which is a low-molecular-weight compound having a molecular weight of 250 to 15,000 obtained through an enzymatic treatment of a fish milt; health foods containing the decomposition system promoter; a method for increasing the responses of various decomposition system-related genes through the oral intake of the decomposition system promoter; and a method for promoting the recycling of cells or the like.

Description

Decomposition system accelerators for enhanced recycling

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

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

[0003] JP 2014-152144 A

[0004] Previous studies have shown that the ingestion of nucleic acids (DNA, RNA) and nuclear proteins exerts various effects, including antioxidant properties. However, there have been no reports to date suggesting that their ingestion affects the degradation of aging cells, oxidized unnecessary proteins within cells, or damaged mitochondria, thereby affecting the recycling of cells themselves or their organelles. Cellular recycling systems include the ubiquitin-proteasome system, which selectively degrades unnecessary or damaged proteins, and autophagy, which involves autophagosome-associated vesicles involved in the self-degradation of damaged or dysfunctional intracellular organelles. Furthermore, the selective removal of damaged mitochondria is called mitophagy. While autophagy is nonselective, the ubiquitin-proteasome system selectively degrades proteins by marking them with ubiquitin. Recent studies have implicated these phenomena in aging and disease. For example, in Drosophila, mutations in autophagy genes have been shown to decrease life expectancy, while overexpression has been shown to increase life expectancy. Furthermore, a relationship between autophagy and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease has been recognized, and it has been reported that impaired autophagy leads to the accumulation of amyloid proteins such as beta-amyloid and alpha-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 formulation for enhancing the recycling of cells and the like, and a method for increasing the responses of various genes related to enhancing the recycling of cells and the like.

[0006] The present invention relates to a degradation system promoter containing a water-soluble nucleoprotein for promoting recycling, particularly a degradation system promoter containing a nucleoprotein degraded to a molecular weight of 250 to 15,000 obtained by enzymatically treating fish milt. 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 a health food containing the degradation system promoter, for example, in the form of a tablet, drinkable supplement, capsule, granule, powder, pill, or jelly. Furthermore, the present invention relates to a method for increasing the response of proteasome-related genes, autophagy-related genes, or apoptosis-related genes by orally ingesting the degradation system promoter, as well as a method for promoting 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.

[0008] The degradation 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 when orally ingested, thereby promoting the degradation and removal of oxidized proteins and organelles such as defective mitochondria, and even cell death itself, thereby achieving the effect of promoting the recycling of these cells, etc. Furthermore, the promotion of recycling is expected to contribute to health maintenance, such as antioxidant properties and disease prevention.

[0009] Figure 1 shows the results of a d-ROMs test performed on the blood of subjects before and after intake of test tablets containing water-soluble nucleoprotein (salmon milt extract) for 8 weeks, and a placebo tablet group in which subjects took placebo tablets not containing the extract for 8 weeks (A) d-ROMs over time (measured values), B) change in d-ROMs (amount of change relative to pre-intake levels). Figure 2 shows the results of a comprehensive gene expression analysis by microarray using total RNA extracted from human blood in human subjects after taking water-soluble nucleoprotein (salmon milt extract) for 8 weeks. FIG. 3 shows the results of a test group in which a water-soluble nuclear protein (salmon milt extract) was added to a culture medium obtained by cultivating yeast (Saccharomyces cerevisiae BY4741 strain (MATa; his3D1; leu2D0; met15D0; ura3D0)) in SD complete liquid medium at 1% water-soluble nuclear protein (salmon milt extract) and a control group in which only a culture medium obtained by cultivating yeast (Saccharomyces cerevisiae (BY4741 strain)) in SD complete liquid medium was added. After 24 hours of treatment, the culture medium was appropriately diluted and inoculated onto a YPD plate medium supplemented with 4 mM hydrogen peroxide, and cultured at 30°C for 72 hours. The graph shows the yeast that survived in the presence of hydrogen peroxide. FIG. 4 shows the results of a test group in which a water-soluble nuclear protein (salmon milt extract) was added to a culture medium obtained by cultivating yeast (Saccharomyces cerevisiae (BY4741 strain)) in SD complete liquid medium at 1% water-soluble nuclear protein (salmon milt extract) and a control group in which only a culture medium obtained by cultivating yeast (Saccharomyces cerevisiae (BY4741 strain)) in SD complete liquid medium was added. Figure 5 shows the survival rate calculated by counting the number of surviving colonies (colonies) after 72 hours of incubation at 30°C in the presence or absence of hydrogen peroxide. Figure 6 shows the results of a 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 yeast (Saccharomyces cerevisiae (BY4741 strain)).

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

[0011] The degradation system promoters of the present invention target the proteasome degradation system, the autophagy degradation system, and apoptosis. These systems are essentially different scales of degradation, with proteasomes selectively degrading defective proteins, autophagy degrading defective proteins and defective intracellular organelles in the cytoplasm, and apoptosis degrading cells themselves (cell death). Accelerating the degradation of these defective cells and converting them into a form that is easily recycled into new cells can lead to enhanced cell recycling. Furthermore, as mentioned above, the proteasome system and autophagy are involved in aging and various diseases, and mutations or declines in these degradation systems can lead to undesirable phenomena such as reduced lifespan. Therefore, promoting autophagy and the proteasome system through the ingestion of nucleic acids (DNA, RNA) and nucleoproteins is expected to have anti-aging and health benefits in addition to simply improving the antioxidant effect of ingesting nucleic acids.

[0012] The water-soluble nuclear protein used in the degradation system promoter of the present invention, as well as in the proteasome-related gene response enhancers, autophagy-related gene response enhancers, and apoptosis-related gene response enhancers described below, and in cell, organelle, or protein recycling enhancers, can be a water-soluble nuclear protein obtained by extracting nucleic acids from biological cells and enzymatically treating them to reduce their molecular weight. In other words, the term "water-soluble nuclear protein" as used herein can be rephrased as a low-molecular-weight extract of fish milt. An example of such a water-soluble nuclear protein is a water-soluble nuclear protein (e.g., salmon milt extract) obtained by enzymatically treating fish milt to reduce its molecular weight. As used herein, "water-soluble" refers to the ability to dissolve in water at a concentration of 0.1% by mass or greater.

[0013] Examples of the fish include salmon, trout, herring, etc. Among these, salmon milt is preferably used, which contains a large amount of nucleic acids but has not been effectively utilized as a resource and much of it has been discarded.

[0014] Examples of enzymatic treatment of fish milt include crushing the milt, treating the resulting suspension with protease, and then treating it with nuclease. Typically, DNA extracted from milt has a molecular weight of 1,000,000 or more, and is then depolymerized by enzymatic treatment. Preferred water-soluble nucleoproteins include those containing nucleosides / nucleotides / oligonucleotides / polynucleotides (hereinafter also referred to as "depolymerized products") having a molecular weight of 250 to 100,000, e.g., 250 to 20,000, 250 to 15,000, 500 to 13,200, or 250 to 10,000, or 250 to 6,600, preferably at a concentration of 20% by mass or more, more preferably 30% by mass or more. More preferably, the water-soluble nucleoprotein (e.g., salmon milt extract) according to the present invention 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 proteases, cysteine ​​proteases, metalloproteases, and aspartic acid proteases. Because fish milt contains proteins other than protamine, proteases with low substrate specificity are particularly preferred. A good example of a protease is the protease manufactured by Novozymes Japan Co., Ltd. Hydrolysis using the protease can be performed at a temperature of 30 to 60°C, e.g., 40 to 50°C, and a pH of 6 to 7, taking into account 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. While there are no particular limitations on the properties of the nuclease, it is preferable for it to have a certain degree of thermostability. 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 consideration 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. After hydrolysis, nucleic acids can be depolymerized by nuclease treatment.

[0016] The present invention also relates to health foods containing the decomposition system accelerator. The health foods of the present invention contain the decomposition system accelerator as an active ingredient, for example, a water-soluble nucleoprotein, which is a low-molecular-weight substance with a molecular weight of 250 to 15,000, for example, 250 to 10,000, obtained by enzymatically treating fish milt, and also contain other ingredients according to the various product forms described below. The content of the recycling agent in the health foods can be adjusted appropriately 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 suits the user's taste. 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 hydroxypropyl cellulose, 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 and the like can also be formulated by conventional means, and are prepared using solvents for the decomposition system accelerators, which are active ingredients, 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 and natural gums such as tragacanth, gum arabic and the like; preservatives such as esters of parahydroxybenzoic acid, benzalkonium chloride, sorbates and the like. Furthermore, the above-mentioned drinks and jellies, as well as dairy products, seasonings, processed foods, desserts, confectioneries, etc. may contain, in addition to their constituent ingredients, oligo-RNA, zinc, collagen, chondroitin, hyaluronic acid, vitamins (vitamins of the B group such as vitamin B1, vitamin B2, vitamin B6, vitamin B12, etc., vitamin C, etc.), glutathione (glutathione-containing yeast extract, reduced glutathione, oxidized glutathione, etc.).More specifically, for example, for drink applications, although not limited to this application, porcine collagen peptides, 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, and porcine placenta extract may be added. Furthermore, for example, for tablet applications, although not limited to this application, brewer's yeast, ginkgo biloba extract, and S-allyl cysteine-containing garlic extract may be added. Furthermore, for example, for jelly applications, although not limited to this application, fish collagen peptides may be added.

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

[0020] The clinical dosage of the decomposition system accelerator of the present invention varies depending on factors such as age, body weight, patient sensitivity, and the severity of symptoms. A typical effective dosage for an adult is, for example, approximately 100 mg to 500 mg of water-soluble nucleoprotein (salmon milt extract) per day. However, amounts 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 foods, the amount of the decomposition system accelerator in the health food can be appropriately adjusted, for example, based on the daily intake of the health food itself and with reference to the above-mentioned daily dosage guidelines.

[0021] The degradation system promoters of the present invention increase the expression of response genes related to the above-mentioned degradation systems, thereby promoting these degradation systems. That is, the present invention also covers methods for increasing the response of proteasome-related genes, autophagy-related genes, and apoptosis-related genes by orally ingesting the degradation promoters. Furthermore, because the degradation of cells and the like ultimately promotes recycling, the present invention also covers methods for promoting the recycling of cells, organelles, or proteins. In these methods for increasing gene response and methods for promoting recycling, the same clinical dosages (recommended dosages) as those for the above-mentioned degradation promoters can be preferably applied as is.

[0022] As described above, the present invention also covers proteasome-related gene response enhancers, autophagy-related gene response enhancers, apoptosis-related gene response enhancers, and cell or organelle recycling enhancers that contain water-soluble nuclear proteins (e.g., salmon milt extract). The present invention also covers cell, organelle, or protein recycling enhancers. 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 degradation promoters described above can be suitably used. These response enhancers and recycling enhancers can also be in the form of health foods containing them. Such health foods can suitably use the same aspects, ingredients, etc. as those described above for health foods containing degradation promoters.

[0023] <Water-soluble nucleoprotein (salmon milt extract)> The water-soluble nucleoprotein (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 a molecular weight range of 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, test tablets (tablets A) containing the water-soluble nucleoprotein (salmon milt extract) obtained in the above Production Example and placebo tablets (tablets B) not containing the extract were produced.

[0025]

[0026] <Test Example (1): Changes in Oxidative Stress Markers> A double-blind, randomized, placebo-controlled study was conducted on 41 healthy subjects (male, no medication, no underlying diseases, etc.) aged 40 to under 60 years. 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 took either tablet A or tablet B for 8 weeks. The test tablet group was administered with a quantity of tablet A adjusted so that the daily intake of water-soluble nucleoprotein (salmon milt extract) was 360 mg (6 tablets per day), and the placebo tablet group was administered with the same amount of tablet B (6 tablets per day) as tablet A. Blood samples were collected from the subjects before and after intake (week 0 and week 8), and a d-ROMs (Reactive Oxygen Metabolites-derived Compounds) test was conducted to comprehensively evaluate the level of oxidative stress in the body by measuring hydroperoxides, which are metabolites of free radicals in the blood. Total RNA was also extracted from the collected blood and subjected to gene expression analysis.

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

[0028] <Test Example (2): Gene Expression Analysis> As in Test Example (1), two groups of subjects, a test tablet group (Tablet A, 20 subjects) and a placebo tablet group (Tablet B, 21 subjects), were administered each tablet for 8 weeks. Total RNA was then extracted from blood collected from the subjects, and comprehensive gene expression analysis was performed. The conditions for the comprehensive gene expression analysis were as follows: <Comprehensive Gene Expression Analysis Using Microarrays> Microarray used: Thermofisher Applied Biosystems (registered trademark) Clariom S Array, Human. 1. Total RNA quality check (RNA degradation evaluation) 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 a RIN value of 7.0 or more were used for the test. 3. cRNA synthesis was performed using the GeneChip WT Plus Reagent Kit. Using 100 ng of total RNA as a template, first-strand cDNA was synthesized by reverse transcription, followed by second-strand cDNA synthesis. Subsequently, cRNA was synthesized by in vitro transcription. After purification, the cRNA yield 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. After synthesis, the 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 the Clariom S Array, Human was performed using the GeneChip Hybridization, Wash, and Stain Kit (Thermo Fisher Scientific). The fragmented and labeled ssDNA was added to hybridization buffer and hybridized on the 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 Expression Console. TM A CHP file was created using the software. 7. Using the Transcriptome Analysis Console (Thermo Fisher Scientific), a ratio of change in transcripts of 1.3 or higher was evaluated and pathway analysis was performed. Table 2 shows the results of gene expression analysis related to various degradation systems (proteasome, autophagy, apoptosis). Figure 2 also shows the results of comprehensive gene expression analysis in the proteasome degradation system and autophagy.

[0029]

[0030] As shown in Table 2, it was confirmed that the test tablet group that took tablet A containing water-soluble nucleoprotein (salmon milt extract) for 8 weeks significantly increased the expression of genes related to various degradation 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 a -80°C stock of the BY4741 strain on a plate, picking 2-3 independent colonies, and culturing them in SD complete medium for 18 hours with shaking (160 rpm, 30°C) to enrich them. A test group was prepared by adding 1 / 10 the volume of the yeast culture solution and the water-soluble nucleoprotein (salmon milt extract) to a fresh SD complete liquid medium at a concentration of 1% relative to the medium, and a control group was prepared by adding only the SD complete liquid medium supplemented with the yeast (water-soluble nucleoprotein (salmon milt extract)). Each group was cultured for 24 hours. After 24 hours of incubation, the yeast culture was washed twice with sterile distilled water to remove the water-soluble nucleoprotein (salmon milt extract). The culture was then diluted appropriately to obtain independent colonies and inoculated onto YPD plates supplemented with 4 mM hydrogen peroxide. After 72 hours of incubation at 30°C, the number of yeast colonies surviving in the presence of hydrogen peroxide was counted. Figure 3 shows the appearance of the test and control groups after 72 hours of incubation. As shown in Figure 3, more colonies were observed in the test group containing water-soluble nucleoprotein (salmon milt extract) than in the control group without water-soluble nucleoprotein (salmon milt extract).

[0032] Similarly to the hydrogen peroxide-added system, systems without hydrogen peroxide (no hydrogen peroxide addition) [yeast + water-soluble nucleoprotein (salmon milt extract) group, yeast only (no water-soluble nucleoprotein (salmon milt extract) added group] were also cultured at 30°C for 72 hours. The number of colonies growing in each medium was counted, and the number of colonies in the hydrogen peroxide-added medium was divided by the number of colonies in the hydrogen peroxide-free medium for both the addition and non-addition of water-soluble nucleoprotein (salmon milt extract) to calculate the yeast survival rate (%). The results are shown in Figure 4. As shown in Figure 4, the survival rate of the yeast with the addition of water-soluble nucleoprotein (salmon milt extract) was significantly higher than that of the yeast without the addition of water-soluble nucleoprotein (salmon milt extract).

[0033] Test Example (4) Comprehensive Gene Expression Analysis by Microarray Using Yeast> 1% of the above water-soluble nuclear protein (salmon milt extract) was added to yeast (Saccharomyces cerevisiae (BY4741 strain (MATa; his3D1; leu2D0; met15D0; ura3D0)), and 24 hours later, a comprehensive gene expression analysis was performed by microarray using 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. A labeling reaction was performed using 250 ng of total RNA each using the GeneChip (registered trademark) 3' IVT PLIS Kit, followed by hybridization. 3. Expression Console TM The RMA algorithm was used to quantify the signal, and the quantified signal values ​​were normalized using the quantile method. 4. Using the Transcriptome Analysis Console (Thermo Fisher Scientific), the ratio of change in transcripts was evaluated at 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]

[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 degradation systems compared to the placebo (no addition) group.

[0036] These 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 the promotion of 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 degradation system promoter containing a water-soluble nucleoprotein for enhancing recycling.

2. The decomposition system accelerator according to claim 1, wherein the water-soluble nuclear protein is a low molecular weight nuclear protein having a molecular weight of 250 to 15,000 obtained by enzymatically treating fish milt.

3. A decomposition system promoter according to claim 1 or claim 2, wherein the decomposition system is a proteasome decomposition system.

4. A decomposition system promoter according to claim 1 or claim 2, wherein the decomposition system is an autophagy decomposition system.

5. The decomposition system promoter according to claim 1 or 2, wherein the decomposition system is apoptosis.

6. A health food comprising the decomposition promoter according to any one of claims 1 to 5.

7. 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.

8. A method for increasing the response of proteasome-related genes by orally ingesting the degradation system promoter described in claim 1 or 2.

9. A method for increasing the response of autophagy-related genes by orally ingesting the decomposition system promoter described in claim 1 or 2.

10. A method for increasing the response of apoptosis-related genes by orally ingesting the decomposition system promoter described in claim 1 or 2.

11. A method for enhancing the recycling of cells, organelles, or proteins by orally ingesting the decomposition promoter described in claim 1 or 2.

12. A response enhancer of proteasome-related genes, comprising a water-soluble nuclear protein.

13. A response enhancer of autophagy-related genes containing a soluble nuclear protein.

14. A response enhancer of apoptosis-related genes, comprising a water-soluble nuclear protein.

15. A recycling enhancer for cells, organelles or proteins containing water-soluble nuclear proteins.

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