JP2013112636A - Sirtuin 1 (sirt1) gene activator, and telomerase reverse transcriptase (tert) gene activator - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a sirtuin 1 (SIRT1) gene activator, and a telomerase reverse transcriptase (TERT) gene activator.SOLUTION: The sirtuin 1 (SIRT1) gene activator and the telomerase reverse transcriptase (TERT) gene activator contain a pinecone lignin glucoside as an active ingredient.

Description

  The present invention relates to a sirtuin 1 (SIRT1) gene activator and a telomerase reverse transcriptase (TERT) gene activator.

Sirtuins are deacetylases consisting of SIRT1-7. In recent years, research on the function of sirtuins has become active. In particular, sirtuin 1 (SIRT1) has an anti-aging effect, diabetes improvement effect, cardiovascular protection effect, renal disease improvement effect, inflammatory cytokine production suppression effect, neuroprotective effect. It became clear that it has various functions.
Compounds such as resveratrol and quercetin have been developed as factors that enhance SIRT1 deacetylation activity, and anti-aging agents (anti-aging agents), diabetes treatment drugs, cardiovascular disease treatment drugs, neurological disease treatment drugs In order to use it as an anti-inflammatory agent, active research has been conducted (for example, see Non-Patent Document 1).

Experimental Medicine 2010, Vol. 28, No. 19, 3068-3076

  An object of the present invention is to provide a sirtuin 1 (SIRT1) gene activator and a telomerase reverse transcriptase (TERT) gene activator.

One embodiment of the present invention is a sirtuin 1 (SIRT1) gene activator containing lignin glycoside as an active ingredient, and the lignin glycoside has the following properties.
(1) Lignin and polysaccharide are bound (2) Molecular weight is 8000 to 10,000
(3) The binding ratio between lignin and polysaccharide is 1: 1 to 2: 1 (molecular ratio).
(4) The polysaccharide is composed of 10-20% uronic acid and 80-90% neutral sugar.

  The lignin glycoside is isolated in the following steps.

(1) A process of hydrothermally treating pine cones of pine needles (2) A step of ethanol-treating the pine cones treated with hot water (3) A step of drying the pine cones subjected to ethanol treatment (4) A sodium hydroxide solution of the dried pine cones (5) Step of neutralizing the extract (6) Step of recovering precipitate by adding ethanol to the extract neutralized in (3) (7) Precipitate To obtain a sirtuin 1 (SIRT1) gene activation fraction.

The lignin glycoside is presumed to have the following structural formula as a partial structure.

  Another embodiment of the present invention includes an anti-aging agent, a therapeutic agent and a preventive agent for diabetes, a therapeutic agent and a preventive agent for cardiovascular diseases, a therapeutic agent and a preventive agent for nervous system diseases, a therapeutic agent and a preventive agent for renal diseases, and an anti It is a pharmaceutical used as any one or more of inflammatory agents, and contains the above lignin glycoside as an active ingredient. The diabetes may be type 2 diabetes, the cardiovascular disease may be myocardial infarction or arteriosclerosis, and the nervous system disease is amyotrophic lateral sclerosis, Alzheimer's disease, or dementia. May be. The renal disease may be nephrosis or renal dysfunction, and the inflammation may be pneumonia, hepatitis, or pancreatitis.

  Another embodiment of the present invention is an NF-kappaB inhibitor containing the above lignin glycoside as an active ingredient.

  Another embodiment of the present invention is a cosmetic composition, containing the above lignin glycoside as an active ingredient.

  Another embodiment of the present invention is a telomerase reverse transcriptase (TERT) gene activator, which contains the above lignin glycoside as an active ingredient.

  Another embodiment of the present invention is a sirtuin 1 (SIRT1) gene activator comprising the lignin glycoside, resveratrol or quercetin as an active ingredient, and activating other sirtuin 1 (SIRT1) You may use together with an agent. The lignin glycoside, resveratrol or quercetin may be contained as an active ingredient, and may be used in combination with other sirtuin 1 (SIRT1) activators and / or sirtuin 1 (SIRT1) gene activators.

  In the present specification, the term “SIRT1 activity” means SIRT1 deacetylation activity.

  According to the present invention, it has become possible to provide a sirtuin 1 (SIRT1) gene activator and a telomerase reverse transcriptase (TERT) gene activator.

In one example of the present invention, a graph comparing the ability of pine cone lignin glycosides to activate the SIRT1 gene promoter with that of resveratrol or quercetin, and the concentration of pine cone lignin glycosides in the culture solution It is the graph which showed the correlation with the promoter activation of SIRT1 gene. In one embodiment of the present invention, a graph comparing the ability of pine cone lignin glycosides to activate the TERT gene promoter with that of resveratrol or quercetin, and the concentration of pine cone lignin glycosides in the culture solution It is the graph which showed the correlation with the promoter activation of a TERT gene.

  The objects, features, advantages, and ideas of the present invention will be apparent to those skilled in the art from the description of the present specification, and those skilled in the art can easily reproduce the present invention from the description of the present specification. The embodiments and specific examples of the invention described below show preferred embodiments of the present invention, and are shown for illustration or explanation. It is not limited. It will be apparent to those skilled in the art that various modifications and variations can be made based on the description of the present specification within the spirit and scope of the present invention disclosed herein.

(1) Pine cone lignin glycoside The compound contained in the sirtuin 1 (SIRT1) gene activator of the present invention is a kind of lignin glycoside contained in a pine family plant, and has the following properties.
(I) Lignin and polysaccharide are bound (II) Molecular weight is 8000 to 10,000
(III) The binding ratio between lignin and polysaccharide is 1: 1 to 2: 1 (molecular ratio).
(IV) The polysaccharide is composed of 10 to 20% uronic acid and 80 to 90% neutral sugar. Examples of neutral sugars include glucose, galactose, mannose, and arabinose.

  This lignin glycoside can be identified by the following extraction method from pine cones.

(I) Hot water treatment First, a pine cone of Goyo pine is hydrothermally treated. The amount of water may be appropriately determined according to the amount of pine cones. Although the temperature of water is not specifically limited, 90 degreeC or more is preferable and 100 degreeC is more preferable. The treatment time is not particularly limited, and the treatment may be performed several times from 1 hour to 1 day, but it is preferable to perform the treatment for 3 hours.
(II) Ethanol treatment Next, the hot water-treated pine cone is treated with ethanol. The amount of ethanol may be appropriately determined according to the amount of pinecone. Pine cones are preferably immersed in 100% ethanol in a dry state, and may be allowed to stand for 1 hour to 1 day, but are preferably allowed to stand at room temperature for 2 hours.
(III) Drying treatment The ethanol-treated pine cone is washed with acetone to remove the ethanol. The amount of acetone may be appropriately determined according to the amount of pine cone. Then leave it to dry the pine cones.
(IV) Sodium hydroxide treatment The dried pine cone is treated with sodium hydroxide to obtain an extract. The amount of sodium hydroxide may be appropriately determined according to the amount of pine cone. The concentration of sodium hydroxide is not particularly limited, but is preferably 0.1N to 1N, and more preferably 0.3N. The treatment time may be left for 1 hour to 1 day, but is preferably left at room temperature for 1 day. Thereafter, the pine cone is removed and the extract is recovered.
(V) Neutralization treatment The extract thus obtained is neutralized. The acid to be used is not particularly limited, but hydrochloric acid or acetic acid is preferable. The final pH is preferably 5-6, and more preferably 5.5.
(VI) Ethanol precipitation Ethanol is added to the neutralized extract, preferably left at 4 ° C. for 1 hour to 1 day to precipitate lignin glycosides, and suction filtered to remove the supernatant.
(VII) Purification Finally, the precipitate is purified. For example, fractionation is performed by gel filtration, and each fraction is evaluated by luciferase assay using the SIRT1 gene promoter to evaluate the SIRT1 gene promoter activation activity, and the active fraction sirtuin 1 (SIRT1) gene activation fraction Can be obtained.

The lignin glycoside extracted in this way (referred to herein as pine cone lignin glycoside) is presumed to have the following structural formula as a partial structure.

  The production method of the above-mentioned pine cone lignin glycoside is a method for identifying the pine cone lignin glycoside used in the present invention, and the extraction method when this pine cone lignin glycoside is actually used is not particularly limited, and is a known method. Should be used. For example, the extraction methods described in Japanese Patent Publication No. 278260 and Japanese Patent Publication No. 2784605 can be used.

(2) Sirtuin 1 (SIRT1) gene activator Since the pine saccharin lignin glycoside can activate the expression of the sirtuin 1 (SIRT1) gene, a pharmaceutical composition (pharmaceutical composition and reagent product composition), It can be used as a food composition or a cosmetic composition, and can be used as a sirtuin 1 (SIRT1) gene activator by formulating these compositions. In this specification, “gene activation” is synonymous with “enhancement of gene expression”. Here, the SIRT1 gene may be derived from humans or non-human mammals.

  SIRT1 has various functions such as aging prevention (anti-aging) action, diabetes improvement action, cardiovascular protection action, kidney disease improvement action, inflammatory cytokine production suppression action, neuroprotection action, etc. By activating the SIRT1 gene and increasing the concentration of SIRT1 in the body, it is possible to exert an anti-aging effect, diabetes-improving effect, cardiovascular protective effect, inflammatory cytokine suppressing effect, neuroprotective effect, and the like. Therefore, SIRT1 gene activator containing pine cone lignin glycoside as an active ingredient is an anti-aging agent (anti-aging) agent, a diabetic therapeutic agent and a preventive agent, a cardiovascular disease therapeutic agent and a preventive agent, a nervous system disease therapeutic agent And a preventive agent, a renal disease therapeutic agent and preventive agent, and an anti-inflammatory agent. Specific target diseases include, for example, diabetes such as type 2 diabetes, cardiovascular diseases such as arteriosclerosis and myocardial infarction, neurological diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, or dementia, nephrosis or Examples include renal diseases such as renal dysfunction, and various inflammatory diseases such as pneumonia, hepatitis, and pancreatitis. In particular, these target diseases are effective against the “senile disease”, which is a systemic disease caused by a decline in the function of multiple organs (heart, liver, pancreas, kidney, etc.) It is extremely effective in that the disease can be treated or prevented centrally. Thus, the SIRT1 gene activator containing pine cone lignin glycoside as an active ingredient is expected to fundamentally change the way of medical care for the elderly.

  Since SIRT1 has an NF-kappaB inhibitory action, the pine cone lignin glycoside can also be used as an NF-kappaB inhibitor. Pine cone lignin glycoside activates NO signal through NF-kappaB suppression and suppresses inflammatory cytokines such as TNFalfa, ICAM-1, IL-6, IL-1 and inducible NOS (i-NOS) Therefore, at least a part of the cardiovascular protective action and anti-inflammatory action is considered to be due to this NF-kappaB inhibitory action.

(3) Telomerase reverse transcriptase (TERT) gene activator Telomerase is a complex consisting of TERC (Telomere RNA Component), a template for telomere sequences, reverse transcriptase (TERT), and regulatory subunits such as dyskerin and TEP1. It is.

  Pine cone lignin glycoside can activate the expression of TERT gene, so it can be used as a pharmaceutical composition (pharmaceutical composition and reagent product composition), food composition, or cosmetic composition. By formulating the composition, it can be used as a telomerase gene activator. Here, the TERT gene may be derived from humans or non-human mammals.

  Cells and living bodies are known to have shortened telomeres as they age, and by activating expression of the telomerase gene, an anti-aging effect can be obtained (JAMA. 1998 Jun 3; 279 (21): 1732-5). In progeria, it is known that shortening of telomeres is accelerated, and treatment of progeria becomes possible by activating expression of the telomerase gene. Therefore, a telomerase gene activator containing pine cone lignin glycoside as an active ingredient is effective as an anti-aging (aging prevention) agent and a progeria treatment agent.

(4) Use of pine cone lignin glycosides Pine cone lignin glycosides can be used in pharmaceutical compositions (pharmaceutical compositions and reagent product compositions), food and beverage compositions, cosmetic compositions, and the like. It can be used to produce foods and drinks, medicines (medicines and reagents) and cosmetics using methods well known to those skilled in the art. As a raw material of these compositions, a purified pine cone lignin glycoside may be used, but an extract such as pine cone mixed with impurities may be used. For example, in the purification method, (VI) You may use the extract which performed until ethanol precipitation. Here, the pine derived from the pine cone is not particularly limited as long as it contains a pine cone lignin glycoside, but particularly Japanese pine containing a large amount of the pine cone lignin glycoside is preferable.

  Although there is no restriction | limiting in particular as food / beverage products containing a pine cone lignin glycoside, It is preferable to add to existing food / beverage products as an additive from simplicity. In addition, you may use the other additive etc. which are used normally in manufacturing the food / beverage products containing a pine cone lignin glycoside.

  Pine cone lignin glycosides as foods and drinks can be used as supplements, nutritional supplements, health supplements, functional foods, health functional foods, foods for specified health use, nutritional functional foods, etc. Or as a supplement. Examples of the food and drink include confectionery such as chocolate, biscuits, gum, candy, cookies, gummi, and tableted confectionery, cereals, powdered drinks, soft drinks, milk drinks, nutrition drinks, carbonated drinks, jelly drinks, and the like, Ice cream, sherbet and other frozen desserts. Further, in the case of food for specified health use, dietary supplement, etc., any form such as powder, granule, capsule, syrup, tablet, sugar-coated tablet, etc. may be used.

  As a medicine containing a pine cone lignin glycoside, any of the diseases described in (2) and (3) can be targeted. A method known to those skilled in the art may be used for the production of the medicine, and the shape is not particularly limited, and may be a tablet, capsule, bagging, syrup, suppository, bottling, ointment and the like.

  Reagents containing pine cone lignin glycosides can also be used as various research reagents in vitro or in vivo. The purpose is not limited, and may be, for example, drug development or basic research. Moreover, the object to be used is not limited, and for example, it may be extracted from a cell, a cell, or a living body.

  Moreover, although the cosmetics containing a pine cone lignin glycoside can also be manufactured, the shape in particular is not restrict | limited, An emulsifier, a gel, a lotion, or a powder is mentioned. In the cosmetic, various main ingredients and auxiliaries usually used in the production of cosmetics and other components can be used as long as the effects of the present invention are not impaired.

(5) Other sirtuin 1 (SIRT1) gene activator and telomerase reverse transcriptase (TERT) gene activator The SIRT1 gene activator and TERT gene activator of the present invention contain resveratrol or quercetin. May be. Therefore, resveratrol and quercetin can be used in pharmaceutical compositions (pharmaceutical compositions and reagent product compositions), food and beverage compositions, cosmetic compositions, etc., each using methods well known to those skilled in the art. Can be used to produce food, drink, medicine and cosmetics. Specific embodiments thereof are the same as those described in (4).

(6) Combined use of SIRT1 activator and SIRT1 gene activator As previously known, resveratrol and quercetin have the ability to activate SIRT1, and clarified in this specification Glycosides, resveratrol, and quercetin have the ability to activate SIRT1 gene.

  In order to obtain a stronger activity of SIRT1, a SIRT1 activator and a SIRT1 gene activator may be used in combination. This is because the effect of SIRT1 is synergistically enhanced by combining drugs with different mechanisms. For example, in combination with SIRT1 gene activator, pine cone lignin glycoside and SIRT1 activator, resveratrol, quercetin, ptein, pyrroloquinosaline, oxazolopyridine, or SRT1720, SIRT1 gene activator A combination of a resveratrol and a SIRT1 activator, quercetin, ptein, pyrroloquinosaline, oxazolopyridine, or SRT1720, a SIRT1 gene activator, quercetin, and a SIRT1 activator, resveratrol, A combination with ptein, pyrroloquinosaline, oxazolopyridine, or SRT1720 is conceivable.

  Here, the SIRT1 activator and the SIRT1 gene activator may be used together as a single agent or in combination as a composite agent. When used in combination as a single agent, it is preferable to administer the SIRT1 activator and the SIRT1 gene activator simultaneously, but “simultaneous” may or may not be exactly the same in time. Means administration of the other while effective.

(7) Combined use of TERT gene activator and SIRT1 activator and / or SIRT1 gene activator Matsukasa lignin glycoside, resveratrol, and quercetin have the ability to activate SIRT1 gene while activating the TERT gene Have the ability. Both of these effects bring about an anti-aging effect, but the mechanism is different. Therefore, the combined effect of the TERT gene activator and SIRT1 activator or SIRT1 gene activator is synergistically enhanced. For example, a pinecone lignin glycoside that is a TERT gene activator and resveratrol, quercetin, ptein, pyrroloquinosaline, oxazolopyridine, or SRT1720 that are SIRT1 activators, or resveratrol that is a SIRT1 gene activator , Or a combination with quercetin, resveratrol, which is a TERT gene activator, and quercetin, ptein, pyrroloquinosaline, oxazolopyridine, or SRT1720, which is a SIRT1 activator, or a pine cone lignin glycoside, which is a SIRT1 gene activator Or quercetin, TERT gene activator quercetin and SIRT1 activator resveratrol, ptein, pyrroloquinosaline, oxazolopyridine, or SRT1720 or SIRT1 gene activator pine bulk lignin Glycosides or Such as the combination of veratrole can be considered.

  Further, the TERT gene activator, SIRT1 gene activator and SIRT1 activator may be used in combination. For example, a combination of a pine cone lignin glycoside as a TERT gene activator, resveratrol as a SIRT1 gene activator, and quercetin, ptein, pyrroloquinosaline, oxazolopyridine, or SRT1720 as a SIRT1 activator, Combination of TERT gene activator pine cone lignin glycoside, SIRT1 gene activator quercetin and SIRT1 activator resveratrol, ptein, pyrroloquinosaline, oxazolopyridine, or SRT1720, TERT gene Combined use of resveratrol, an activator, pine cone lignin glycoside, an SIRT1 gene activator, and quercetin, ptein, pyrroloquinosaline, oxazolopyridine, or SRT1720, SIRT1 activator, TERT gene activation Resveratrol, a drug, and SIRT1 gene activator Combined use of lucetin with SIRT1 activator ptein, pyrroloquinosaline, oxazolopyridine, or SRT1720, TERT gene activator quercetin, SIRT1 gene activator pine cone lignin glycoside, and SIRT1 activity In combination with resveratrol, ptein, pyrroloquinosaline, oxazolopyridine, or SRT1720, or TERT gene activator, quercetin, SIRT1 gene activator resveratrol, and SIRT1 activator A combination with a certain ptein, pyrroloquinosaline, oxazolopyridine, or SRT1720 is conceivable.

  Here, the TERT gene activator and SIRT1 activator and / or SIRT1 gene activator may be used in combination as a single agent or in combination as a composite agent. When used in combination as a single agent, it is preferable to administer the TERT gene activator and SIRT1 activator and / or SIRT1 gene activator at the same time, but "simultaneous" is the same even if they are exactly the same in time This may not be the case, meaning that the other is administered while one effect is present, or the other is administered while two effects are present.

(7) How to use food and drink, medicine (medicine and reagent), and cosmetics Like food, you can drink and eat. As supplementary foods, in addition to a normal meal or diet, an appropriate amount may be taken regularly. In addition, even if the person who eats or eats and the mammal other than a human are healthy, they may suffer from the disease as described in (2) or (3).
The administration target of the pharmaceutical containing the pine cone lignin glycoside is a human or a non-human mammal suffering from the disease described in (2) or (3). The administration method is not limited, and it may be oral, parenteral, systemic administration, or local administration.
Reagent products containing pine cone lignin glycosides can be used in vivo such as in mammals other than humans and in vitro such as cultured cells and cultured tissues.
Cosmetics containing pine cone lignin glycosides can be used in the same manner as ordinary cosmetics. The human being used may be healthy or may suffer from the diseases described in (2) and (3).

(1) Preparation of pine cone lignin glycoside 100 g of pine cone of pine needle pine was placed in 1 L of hot water, left for 2 hours, the hot water was changed, and the same treatment was repeated twice. In a semi-dry state, it was immersed in 1 L of 100% ethanol and allowed to stand at room temperature for 2 hours. Then, it wash | cleaned with 300 mL acetone, and left still at room temperature all day and night and dried.
The pine cone pretreated in this way was immersed in 1 L of 0.3N sodium hydroxide and allowed to stand at room temperature all day and night, and then the pine cone was filtered and removed. 2N hydrochloric acid was added dropwise to the resulting extract to adjust the pH to 5.5. An equal amount of 100% ethanol was added to this solution and allowed to stand at 4 ° C. overnight. The generated precipitate was collected by suction filtration, dissolved in an equal amount of water at a weight / volume ratio, dialyzed against a large amount of water for 24 hours, and then freeze-dried to obtain a powder. .

This powder was dissolved in 1 mL of water and purified by column chromatography (Sepharose CL-4B). For each of the obtained fractions, the SIRT1 gene promoter activation effect was evaluated by luciferase assay using the SIRT1 gene promoter, the active fraction was collected, and after dialysis against water, the obtained solution was again used. Lyophilized to obtain a powder.
This powder was dissolved in 1 mL of 10% ethanol and purified by column chromatography (Toyopearl HW40-F). The active fraction identified in the same manner as above was collected and dialyzed against water, and then the resulting solution was freeze-dried again to obtain 0.18 g of a powder containing pine cone lignin glycoside.

(2) Luciferase Assay Using SIRT1 Gene and TERT Gene Promoter First, firefly luciferase reporter plasmid pGL4.10 [Luc2] (Promega) was digested with restriction enzyme Kpn I and restriction enzyme Xho I, and NT_030059 By inserting a nucleotide sequence corresponding to human SIRT1 gene promoter from 20448573 to 20448961 in .13 or a nucleotide sequence corresponding to human TERT gene promoter from 1285126 to 1285385 in NT_006576.16 A reporter plasmid was prepared by inserting the luciferase gene downstream of the gene promoter or TERT gene promoter.

Next, using 10% FCS-containing DMEM (low glucose) as a culture solution, 2 × 10 ⁶ HeLa S3 cells were seeded in a 10 cm dish and cultured under conditions of 5% CO ₂ and 37 ° C. for 24 hours. The cells were transfected with 4 μg of each reporter plasmid using “FuGENE HD Transfection Reagent” (Roche). Furthermore, after culturing for 24 hours, the cells were collected, suspended in the same culture solution so as to be 1 × 10 ⁴ cells / mL, and seeded in a 96-well dish at 100 μL / well. Thereafter, after culturing for 24 hours, the pine cone lignin glycoside was replaced with a culture solution containing final concentrations of 0 (control), 1, 3, 10, 30, 100 μg / mL, and further cultured for 24 hours. Then, after removing the culture solution, 30 μL / well of a lysis reagent “Passive Lysis Buffer” (Promega) was added and repeated freeze-thawing three times. Then, the cell lysate was collected and the residue was removed by centrifugation. The supernatant was recovered. 100 μL of “luciferase assay reagent (II)” (Promega) was added to 20 μL of the obtained supernatant, and the luminescence intensity was measured. The results are shown in FIGS. 1 and 2 (right figure). In addition, as a control experiment, an experiment was conducted using a culture solution to which resveratrol (final concentration: 100 μM) or quercetin (final concentration: 100 μM) was added instead of pine cone lignin glycoside (final concentration: 100 μg / mL). (Left figure).

(3) Results As shown in FIG. 1 and FIG. 2 (left), the conventionally known SIRT1 activator resveratrol or quercetin enhances the transcriptional activity of SIRT1 gene and TERT gene. Glycosides potently enhanced their transcriptional activity.
Moreover, as shown in FIG. 1 and FIG. 2 (right figure), as the concentration of pine cone lignin glycoside in the medium increases, the activity of each promoter increases, and the graph showing the relationship between the concentration and activation shows a sigmoid curve. Painted. Thus, the pine cone lignin glycoside has a concentration-dependent activation action on the promoters of the SIRT1 gene and the TERT gene.
Thus, the pine cone lignin glycoside is effective as a transcription activator of the SIRT1 gene and the TERT gene.

Claims (14)

A sirtuin 1 (SIRT1) gene activator containing lignin glycoside as an active ingredient,
The lignin glycoside has the following properties: a sirtuin 1 (SIRT1) gene activator.
(1) Lignin and polysaccharide are bound (2) Molecular weight is 8000 to 10,000
(3) The binding ratio between lignin and polysaccharide is 1: 1 to 2: 1 (molecular ratio).
(4) The polysaccharide is composed of 10-20% uronic acid and 80-90% neutral sugar. The sirtuin 1 (SIRT1) gene activator according to claim 1, wherein the lignin glycoside is isolated in the following steps.
(1) A process of hydrothermally treating pine cones of pine needles (2) A step of ethanol-treating the pine cones treated with hot water (3) A step of drying the pine cones subjected to ethanol treatment (4) A sodium hydroxide solution of the dried pine cones (5) Step of neutralizing the extract (6) Step of recovering precipitate by adding ethanol to the extract neutralized in (3) (7) Precipitate To obtain a sirtuin 1 (SIRT1) gene activation fraction. The sirtuin 1 (SIRT1) gene activator according to claim 1 or 2, wherein the lignin glycoside has the following structural formula as a partial structure.

Any one or more of an anti-aging agent, a therapeutic agent and a preventive agent for diabetes, a therapeutic agent and a preventive agent for cardiovascular diseases, a therapeutic agent and a preventive agent for nervous system diseases, a therapeutic agent and a preventive agent for renal diseases, and an anti-inflammatory agent A medicine used as
The pharmaceutical which contains the lignin glycoside of any one of Claims 1-3 as an active ingredient.   The medicament according to claim 4, wherein the diabetes is type 2 diabetes.   The medicament according to claim 4, wherein the cardiovascular disease is myocardial infarction or arteriosclerosis.   The medicament according to claim 4, wherein the nervous system disease is amyotrophic lateral sclerosis, Alzheimer's disease, or dementia.   The medicament according to claim 4, wherein the renal disease is nephrosis or renal dysfunction.   The medicament according to claim 4, wherein the inflammation is pneumonia, hepatitis, or pancreatitis.   The NF-kappaB inhibitor which contains the lignin glycoside of any one of Claims 1-3 as an active ingredient.   A cosmetic composition containing the lignin glycoside according to any one of claims 1 to 3 as an active ingredient.   The telomerase reverse transcriptase (TERT) gene activator which contains the lignin glycoside of any one of Claims 1-3 as an active ingredient.   A sirtuin comprising the lignin glycoside, resveratrol or quercetin according to any one of claims 1 to 3 as an active ingredient, and used in combination with another sirtuin 1 (SIRT1) activator. 1 (SIRT1) gene activator.   The lignin glycoside, resveratrol or quercetin according to any one of claims 1 to 3 is contained as an active ingredient, and other sirtuin 1 (SIRT1) activator and / or sirtuin 1 (SIRT1) gene activity A telomerase reverse transcriptase (TERT) gene activator characterized by being used in combination with an agent.

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