CN111214465A - Anti-aging application of verapamil - Google Patents

Abstract

The invention provides an anti-aging application of verapamil. Specifically, the invention provides the application of verapamil or an optical isomer thereof or a pharmaceutically acceptable salt thereof in preparing an anti-aging composition or preparation. Experiments of the invention show that verapamil can significantly prolong the life of nematodes; the evaluation experiment of the health parameters of the nematode proves that the verapamil can improve the movement behavior ability, the body swing ability and the osmotic stress ability of the nematode and reduce the integrity defect of the vulva; the aging cell staining experiment proves that verapamil can reduce the aging rate of human embryonic lung cells. Therefore, verapamil can be applied to aspects of prolonging the life, delaying aging, improving healthy physiological parameters, reducing the incidence rate of aging-related diseases and the like. The invention also provides products such as anti-aging drugs, health products, cosmetics and the like.

Description

Anti-aging application of verapamil

Technical Field

The invention relates to the field of medicines, in particular to an anti-aging application of verapamil.

Background

Aging is a complex and variable progressive process, is influenced by various mechanisms, and has the defects of injury, metabolism and stress response capability reduction along with the continuous increase of the age of the functions of various tissues and organs of an organism, and is often accompanied by diabetes, tumors, cardiovascular diseases, neurodegenerative diseases and the like. Aging and aging-related diseases seriously threaten the human life health and quality of life and aggravate the social medical burden. Although aging is irreversible, it is possible to achieve aging delay, which is the most effective intervention strategy to effectively delay aging, extend the health life, and reduce the incidence of aging-related diseases by anti-aging drugs.

The development of anti-aging drugs aims to improve the life efficiency, i.e., survival time and vitality. Under the current situation of 'population aging' and the background of 'implementing healthy Chinese strategy', the research and development of anti-aging drugs have important significance.

However, satisfactory anti-aging drugs are currently lacking, and therefore, there is an urgent need in the art to develop new safe and effective anti-aging methods and pharmaceutical compositions.

Disclosure of Invention

The object of the present invention is to provide a safe and effective anti-aging method and pharmaceutical composition.

In a first aspect of the invention, there is provided the use of verapamil, or an optical isomer thereof, or a pharmaceutically acceptable salt thereof, for the preparation of a composition or formulation for anti-aging.

In another preferred embodiment, the composition or formulation is for one or more applications selected from the group consisting of:

(i) delaying or reversing normal somatic cell senescence;

(ii) reducing the expression amount of SA- β -Gal;

(iii) increasing the healthy level of cells and organisms, or improving healthy physiological parameters;

(iv) improving or improving locomotor activity, or body swing;

(v) improving the stress ability.

In another preferred embodiment, the composition is a pharmaceutical composition, a cosmetic composition, a dietary supplement, a food composition, a nutraceutical composition.

In another preferred embodiment, the preparation comprises dietary supplements, food additives and test reagents.

In another preferred embodiment, the pharmaceutical composition comprises (a) verapamil or a pharmaceutically acceptable salt thereof as an active ingredient; and (b) a pharmaceutically acceptable carrier or excipient.

In another preferred embodiment, the pharmaceutical composition further comprises an additional anti-aging active ingredient.

In another preferred embodiment, the verapamil is present in the pharmaceutical composition in an amount of 0.001 to 99 wt%, preferably 0.01 to 90 wt%, based on the total weight of the composition.

In another preferred embodiment, the pharmaceutical composition is an injectable or oral drug.

In another preferred embodiment, the pharmaceutical composition is in a form selected from the group consisting of: tablets, capsules, granules, suspensions, pills, solutions, syrups, or injections.

In another preferred embodiment, the composition or formulation is administered to a mammal, or a nematode.

In another preferred embodiment, the mammal comprises: a primate; more preferably the mammal is a human.

In another preferred embodiment, the cell is a somatic cell.

In another preferred embodiment, the cell is selected from the group consisting of: fibroblasts, vascular endothelial cells, epithelial cells (including skin epithelial cells), lung cells, liver cells, or combinations thereof.

In another preferred embodiment, the anti-aging includes anti-aging of skin.

In a second aspect of the present invention, a cosmetic composition or product is provided, which contains verapamil as an anti-aging active ingredient.

In another preferred embodiment, the cosmetic composition or product comprises verapamil in an amount of 0.001 to 99% by weight, preferably 0.01 to 90% by weight.

in a third aspect of the invention, there is provided an in vitro non-therapeutic method of reducing the expression of SA- β -Gal protein, said method comprising the steps of:

adding verapamil or a salt thereof to a cell culture system, thereby reducing the amount of SA- β -Gal protein expressed in the cells;

or culturing the cell in the presence of verapamil or a salt thereof, thereby reducing the expression amount of SA- β -Gal protein in the cell.

In another preferred embodiment, verapamil is present in the culture system at a concentration of 0.1-500. mu.M, preferably 0.5-200. mu.M, more preferably 1-50. mu.M, most preferably 2-20. mu.M.

In another preferred embodiment, the cell is a eukaryotic cell.

In another preferred embodiment, the cells are derived from a mammal, preferably human cells.

In another preferred embodiment, the cell is a somatic cell.

In another preferred embodiment, the cell is selected from the group consisting of: fibroblasts, vascular endothelial cells, epithelial cells (including skin epithelial cells), lung cells, liver cells, or combinations thereof.

In a fourth aspect of the present invention, there is provided an anti-aging method comprising the steps of: verapamil, or an optical isomer thereof, or a pharmaceutically acceptable salt thereof, is administered to a subject in need thereof as an anti-aging active ingredient.

In another preferred embodiment, the mammal comprises: a primate; more preferably the mammal is a human.

In a fifth aspect of the present invention, there is provided a pharmaceutical composition for anti-aging, comprising:

(a1) verapamil or a pharmaceutically acceptable salt thereof as an active ingredient;

(a2) an additional anti-aging active selected from the group consisting of: metformin, resveratrol, rapamycin, acarbose, dasatinib, quercetin, curcumin, astaxanthin and arbutin;

(b) a pharmaceutically acceptable carrier or excipient.

In another preferred embodiment, the verapamil is present in the pharmaceutical composition in an amount of 0.001 to 99 wt%, preferably 0.01 to 90 wt%, based on the total weight of the composition.

It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.

Drawings

Figure 1 shows that in one example, verapamil (100 μ Μ, 400 μ Μ) significantly extended nematode longevity (× P <0.001, × P <0.01), wherein figure 1(a) shows nematode survival at day 21 and day 25; FIG. 1(B) shows the survival curves of nematodes.

Figure 2 shows that verapamil improves the healthy physiological parameters of nematodes in example 2. Figure 2(a) shows verapamil elevated locomotor activity, with significantly elevated locomotor activity on day 2 (100 μ M, P < 0.0001; 400 μ M, P < 0.0001). Figure 2(B) shows that verapamil increased body swing capacity, on day 8, verapamil (400 μ M) significantly increased body swing capacity (× P < 0.05); verapamil (100 μ M, 400 μ M) significantly increased body swing capacity at day 12 (. P <0.05,. P < 0.01). Figure 2(C) shows verapamil (400 μ M) significantly elevated osmotic stress capacity (. about.p < 0.01). Figure 2(D) shows that verapamil (100 μ M, 400 μ M) significantly reduced the vulvar integrity defect ratio (×) indicating P < 0.01.

Figure 3 shows that verapamil (3 μ M) significantly reduced the human embryonic lung cell senescence rate in example 3 (. about.p < 0.05).

Detailed Description

The inventor of the invention has conducted extensive and intensive research, and unexpectedly found that verapamil can effectively prolong the life of nematodes and delay or reverse the aging process of normal somatic cells, thereby having an anti-aging function. Further tests also prove that verapamil not only has an anti-aging function, but also can improve the health level of the organism. Therefore, verapamil is a safe and effective anti-aging active ingredient. On the basis of this, the present invention has been completed.

Specifically, nematode life tests prove that the verapamil can remarkably prolong the life of the nematodes by taking the nematodes as model animals. Health parameter evaluation experiments prove that verapamil can improve the movement behavior ability, the body swinging ability and the osmotic stress ability of nematodes and reduce the vulvar integrity defects. The aging cell staining experiment shows that verapamil can reduce the aging rate of human embryonic lung cells.

Term(s) for

As used herein, the terms "active ingredient of the present invention", "antiaging active ingredient of the present invention", "compound of the present invention", "antiaging compound of the present invention" mean verapamil, or a pharmaceutically acceptable salt thereof, or a solvate thereof, or an optical isomer thereof, or a racemate thereof, or a crystal thereof, or a hydrate thereof, or a deuterated compound thereof, or a combination thereof.

as used herein, the term "SA- β -gal" refers to senescence-associated β -galactosidase (senescence-associated β -galactosidase).

Aging and anti-aging

As used herein, "aging" refers to the process of loss and degeneration of an organism in terms of constituent substances, tissue structure, physiological functions, etc., which occurs with time. In the present invention, aging refers to biological aging.

As used herein, "anti-aging" refers to delaying, retarding, reducing, stopping and/or reversing an aging effect or process.

to detect cellular senescence, a cell staining assay is generally used which detects senescence-associated markers (e.g., β -galactosidase activity).

some representative markers or markers of senescence cells include, but are not limited to, SA- β -galactosidase, whose expression increases in an amount indicative of increased senescence, and cell proliferative capacity, whose decrease is indicative of increased senescence.

Caenorhabditis elegans

Caenorhabditis elegans is a classical model organism and has the characteristics of short life cycle, easy observation, clear genetic background and the like. In addition, nematode genes are highly homologous to many important functional genes in humans and have similar signaling pathways, making them of increasing interest in pathology research, new target discovery, and drug screening.

Caenorhabditis elegans is one of the important model organisms for anti-aging research, and has been used for screening anti-aging substances and mechanism research of anti-aging.

Active ingredient

The anti-aging active ingredient of the present invention is verapamil or a pharmaceutically acceptable salt thereof.

Verapamil (verapamil) is a class of phenylalkylamine type calcium channel blockers used clinically to treat hypertension, arrhythmia and angina pectoris. The chemical formula is as follows: c₂₇H₃₈N₂O₄Molecular weight: 454.6110, CAS number: 52-53-9. The structural formula is shown as the formula (I):

in the present invention, a preferred active ingredient is a pharmaceutically acceptable salt of verapamil. A typical pharmaceutically acceptable salt is the hydrochloride salt, verapamil hydrochloride (CAS: 152-11-4). The commonly used verapamil hydrochloride is the hydrochloride salt of 1 equivalent of verapamil with 1 equivalent of hydrochloric acid.

in addition, verapamil mediates the calcineurin-Nuclear Factor (NFY) signaling pathway that regulates myocardial apoptosis and gene transcription affecting the physiological, pathological progression of the heart.

Pharmaceutical compositions and methods of administration

The invention also provides a composition or a preparation or a product containing the active ingredients of the invention, and the composition or the preparation or the product can be used for resisting aging. Representative compositions or formulations or products include anti-aging drugs, nutraceuticals, and cosmetics.

One preferred composition is a pharmaceutical composition comprising an effective amount of verapamil or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

As used herein, the term "effective amount" or "effective dose" refers to an amount that produces a function or activity (i.e., anti-aging function) in a human and/or animal and is acceptable to the human and/or animal.

As used herein, an ingredient of the term "pharmaceutically acceptable" is one that is suitable for use in humans and/or mammals without undue adverse side effects (such as toxicity, irritation, and allergic response), i.e., at a reasonable benefit/risk ratio. The term "pharmaceutically acceptable carrier" refers to a carrier for administration of a therapeutic agent, including various excipients and diluents.

The pharmaceutical composition of the present invention contains a safe and effective amount of the active ingredient of the present invention and a pharmaceutically acceptable carrier. Such vectors include (but are not limited to): saline, buffer, glucose, water, glycerol, ethanol, and combinations thereof. The pharmaceutical composition of the invention can be prepared into injections, oral preparations (tablets, capsules, oral liquids), transdermal agents and sustained-release agents. For example, by a conventional method using physiological saline or an aqueous solution containing glucose and other adjuvants. The pharmaceutical composition is preferably manufactured under sterile conditions.

The effective amount of the active ingredient of the present invention may vary depending on the mode of administration and the severity of the disease to be treated, etc. The selection of a preferred effective amount can be determined by one of ordinary skill in the art based on a variety of factors (e.g., by clinical trials). Such factors include, but are not limited to: pharmacokinetic parameters of the active ingredient such as bioavailability, metabolism, half-life, etc.; the severity of the disease to be treated by the patient, the weight of the patient, the immune status of the patient, the route of administration, and the like. In general, satisfactory results are obtained when the active ingredient of the invention is administered at a daily dose of about 0.00001mg to 50mg per kg of animal body weight (preferably 0.0001mg to 10mg per kg of animal body weight). For example, divided doses may be administered several times per day, or the dose may be proportionally reduced, as may be required by the urgency of the condition being treated.

Typically, when verapamil is administered orally, the daily average dose in a subject (human) of 60kg body weight is usually 10-500mg, preferably 20-300mg, more preferably 50-250 mg. The daily dose may be administered in one, two or more divided doses.

The pharmaceutically acceptable carrier of the present invention includes (but is not limited to): water, saline, liposomes, lipids, peptidic substances, cellulose, nanogels, or combinations thereof. The choice of carrier should be matched with the mode of administration, which is well known to those skilled in the art.

Anti-aging method

the present invention provides an anti-aging method (including therapeutic methods, or in vitro non-therapeutic methods), and methods of inhibiting SA- β -Gal protein expression and/or activity.

typically, the method comprises adding the pharmaceutical composition of the invention or the active ingredient of the invention to a cultured cell system, thereby delaying and/or reversing the senescence process of said cells, or reducing the amount of SA- β -Gal protein expression.

In another preferred embodiment, the cells are somatic cells (physiological cells), particularly normal somatic cells.

The invention also provides an anti-aging method, which comprises the following steps: verapamil, or an optical isomer thereof, or a pharmaceutically acceptable salt thereof, is administered to a subject in need thereof as an anti-aging active ingredient.

Preferably, the anti-aging method is applying (or applying) a cosmetic containing verapamil or a salt thereof to the skin of the subject.

In the present invention, representative cosmetic formulations may be selected from the following group (but are not limited to): solid dosage forms, semi-solid dosage forms, liquid dosage forms, or combinations thereof, such as solutions, gels, creams, lotions, essences, transdermal patches, masks, and the like.

The main advantages of the invention include:

(a) the verapamil is proved to be effective in anti-aging for the first time, and the life of organisms or cells can be remarkably prolonged.

(b) Verapamil not only reduces but also increases the level of cell and body health, for example, improves locomotor activity, body swing and osmotic stress.

(c) At very low (3 μ M) doses, verapamil may exhibit anti-aging effects comparable to 100 μ M metformin.

(d) Verapamil has a high safety in use as an old drug which has been on the market.

Therefore, the verapamil (or the composition and the product containing the verapamil) which is the active ingredient of the present invention can be applied to various aspects such as prolonging the lifespan, delaying aging, improving healthy physiological parameters, reducing the incidence of aging-related diseases, and the like.

The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Experimental procedures without specific conditions noted in the following examples, generally followed by conventional conditions, such as Sambrook et al, molecular cloning: the conditions described in the laboratory Manual (New York: Cold Spring harbor laboratory Press,1989), or according to the manufacturer's recommendations. Unless otherwise indicated, percentages and parts are percentages and parts by weight.

Example 1 nematode longevity test of verapamil

1.1 methods

Verapamil hydrochloride (CAS:152-11-4) available from Shanghai Tantake Technology, Inc.; wild type C.elegans (N2) was purchased from CAENORHABDITIS GENETICS CENTER (CGC).

The synchronized nematodes were transferred to Nematode Growth Medium (NGM) of control blank and verapamil dosed groups (100. mu.M, 400. mu.M) at L4, with about 80-90 nematodes per group, and the medium was changed every 3 days and cultured at 20 ℃. The number of surviving nematodes was recorded daily and the dead nematodes were removed from the plates until all were dead. The data were summarized, survival curves were plotted using GraphPad, and significant differences (Log-rank test) were calculated. Three effective replicates were performed.

1.2 results

The lifetime test data are shown in table 1 and fig. 1.

As shown in fig. 1(a), the survival rates of nematodes in the 100 μ M verapamil-administered group and the 400 μ M verapamil-administered group were significantly higher than those in the control group (no verapamil addition) on days 21 and 25.

Survival curves as shown in fig. 1(B), verapamil significantly extended nematode longevity at dosing concentrations of 100 μ M and 400 μ M. Compared with a control group, the verapamil prolongs the nematode life by 20.59 percent under the concentration of 100 mu M; at a concentration of 400. mu.M, verapamil extended nematode longevity by 19.45%. Significant differences relative to control: denotes P <0.01, denotes P < 0.001.

TABLE 1 Life test data

The results in fig. 1 and table 1 show that verapamil significantly extends nematode longevity compared to the control group.

Example 2 verapamil improves nematode health physiological parameters

2.1 method

In order to further evaluate the influence of verapamil on nematode health parameters, the movement behavior, body swing capacity, vulvar integrity defect and osmotic stress capacity of the nematodes were tested.

Movement behavior experiment of nematodes: culturing nematodes according to a nematode life experiment method, picking 20 to 30 nematodes in adult nematodes in a control group and a verapamil group respectively on days 2, 4, 6, 8, 10, 12 and 14 of the nematodes, recording the crawling track of each nematode within 30 seconds respectively, and processing by ImageJ to obtain the crawling speed of the nematodes. After the experiment was completed, the data were counted and significance differences were calculated using Graph Pad (Two-way ANOVA, Sidak multiple complexes test), with error bars indicating the mean Standard Error (SEM). Three effective replicates were performed.

Nematode body swing ability test: the nematodes were cultured according to the method of nematode longevity test, 20 to 30 nematodes were picked up in the control group and the verapamil group on days 3, 8 and 12 of adult nematodes, and the number of body swings of each nematode in the buffer solution (M9) for 30 seconds was recorded. After the experiment was completed, the data were counted and significance differences were calculated using Graph Pad (Two-way anova, Sidak multiple complexes test), with error bars indicating the mean Standard Error (SEM). Three effective repeated experiments are carried out,

nematode osmotic stress test: and (3) culturing the nematodes according to a nematode life experiment method, wherein on the 6 th day of adult nematodes, about 60 nematodes are picked respectively from the control group and the verapamil group and transferred to a culture medium containing high-concentration NaCl, so that the nematodes are in a high-osmotic-pressure environment. The number of motile nematodes was recorded at 3, 5, 7, 9, 11, 13 minutes, the data was counted, survival curves were plotted using Graph Pad, and the significant difference (Log-rank test) was calculated. Three effective replicates were performed.

Nematode vulva integrity defect experiment: culturing nematodes according to a nematode life test method, 100 nematodes in a control group and a verapamil group respectively, recording the number of nematodes exposed to the outside of intestinal tracts after the vulva integrity defect (Avid) appears in the control group and the verapamil group every day until all the nematodes die, counting the percentage of nematodes with Avid appearing in each group, calculating the significance difference (Unpaired t-test) by using Graph Pad, and marking the error bar with the mean Standard Error (SEM). Three effective replicates were performed.

2.2 results

The results of the experiment are shown in FIG. 2.

Fig. 2 (a): a control group and a verapamil administration group (100. mu.M, 400. mu.M) were set to perform a nematode locomotor activity test. The result shows that the nematode moving capacity is remarkably improved by verapamil (100 mu M and 400 mu M) on day 2, and the verapamil (100 mu M and 400 mu M) has no negative effect on the nematode moving capacity on days 4 to 14. This indicates that verapamil (100 μ M, 400 μ M) can improve nematode locomotor performance.

Fig. 2 (B): a control group and a verapamil administration group (100 mu M and 400 mu M) are set for carrying out nematode body swing experiments, nematodes are respectively picked into M9 buffer solution drops on days 3, 8 and 12, and are made to swing in the drops, and the number of swinging times is counted within 30 s. The results showed that the verapamil dosed groups (100 μ M, 400 μ M) generally increased nematode swing capacity (the 100 μ M dosed group was significantly different at day 12, and the 400 μ M dosed group was significantly different at days 8, 12). This indicates that verapamil contributes to the increase in nematode body swing ability.

Fig. 2 (C): the nematodes were fed for 6 days according to the normal life test, and the nematodes in the control group and the verapamil administration group (100. mu.M, 400. mu.M) were transferred to the medium in the high osmotic environment, and the number of the motile nematodes was counted at 3, 5, 7, 9, 11, and 13 minutes, and a graph was drawn. The result shows that compared with the control group, verapamil (100 mu M) has no negative influence on the high osmotic pressure stress capability, and verapamil (400 mu M) remarkably improves the high osmotic pressure stress capability. This indicates that verapamil contributes to the increase in the osmotic stress capacity of the nematode.

The above results show that verapamil improves the healthy physiological parameters of nematodes in different ways.

Fig. 2 (D): nematode vulvar integrity is an important indicator of nematode health, and defects in vulvar integrity can increase nematode mortality. The control group and the verapamil-dosed group (100. mu.M, 400. mu.M) were set to feed nematodes until all were dead, and the number of nematodes with defective vulvar integrity during the period was counted. The results show that compared with the control group, verapamil (100 mu M and 400 mu M) remarkably reduces the nematode vulva integrity defect ratio and improves the health level.

Example 3 verapamil reduces cellular senescence rate

the vast majority of normal cells are thought to have only a limited ability to divide, enter a senescent state after failing to divide, are usually large in size, and have high activity of β -galactosidase (β -galactosidase), and the degree of cellular senescence can be assessed by staining β -gal with a cytosenescence β -galactosidase staining kit (cloudy day).

in this example, SA- β -Gal was used as a marker for senescent cells and stained with the chemical reagent X-Gal to give a bluish green color.

human embryonic lung cells (MRC-5 purchased in a Chinese academy of sciences cell bank) are cultured in an MEM (MEM) culture medium (containing 10% FBS, 1% sodium pyruvate, 1% nonessential amino acids and 1% double antibody), the cell aging degree is detected by a pre-experiment (P31), the cell aging rate can be tested at 50-60%, the experiment is provided with a control group, a verapamil group (3 MuM) and a metformin group (100 MuM, a positive drug group), the drugs and the cells are incubated for 3 days, the cells can be stained by a β -galactosidase staining kit, the cell nucleus is stained by DAPI (Sigma), the number of aged cells and the total number of aged cells are counted, the cell aging rate is calculated, the significance difference (Ungaired t-test) is calculated by Graph Pad, the mean Standard Error (SEM) is marked, and the experiment is effectively repeated for three times.

The results of the experiment are shown in FIG. 3. Verapamil (3 μ M) significantly reduced the rate of cell senescence compared to the control group, with activity comparable to that of the positive drug metformin (100 μ M). Significant differences relative to control: denotes P < 0.05.

All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Claims (10)

1. Use of verapamil, or an optical isomer thereof, or a pharmaceutically acceptable salt thereof, for the preparation of a composition or formulation for anti-aging.

2. The use of claim 1, wherein the composition or formulation is for one or more applications selected from the group consisting of:

(i) delaying or reversing normal somatic cell senescence;

(ii) reducing the expression amount of SA- β -Gal;

(iii) increasing the healthy level of cells and organisms, or improving healthy physiological parameters;

(iv) improving or improving locomotor activity, or body swing;

(v) improving the stress ability.

3. The use according to claim 1, wherein the composition is a pharmaceutical composition, a cosmetic composition, a dietary supplement, a food composition, a nutraceutical composition.

4. The use according to claim 3, wherein the pharmaceutical composition comprises (a) verapamil or a pharmaceutically acceptable salt thereof as an active ingredient; and (b) a pharmaceutically acceptable carrier or excipient.

5. The use of claim 3, wherein the pharmaceutical composition is an injectable or oral medicament.

6. The use of claim 3, wherein the pharmaceutical composition is in a form selected from the group consisting of: tablets, capsules, granules, suspensions, pills, solutions, syrups, or injections.

7. A cosmetic composition or product characterized in that it contains verapamil as an anti-aging active ingredient.

8. an in vitro non-therapeutic method for reducing the expression level of SA- β -Gal protein, comprising the steps of:

culturing a cell in the presence of verapamil or a salt thereof, thereby reducing the expression level of SA- β -Gal protein in the cell.

9. A method of anti-aging comprising the steps of: verapamil, or an optical isomer thereof, or a pharmaceutically acceptable salt thereof, is administered to a subject in need thereof as an anti-aging active ingredient.

10. A pharmaceutical composition for anti-aging, comprising:

(a1) verapamil or a pharmaceutically acceptable salt thereof as an active ingredient;

(a2) an additional anti-aging active selected from the group consisting of: metformin, resveratrol, rapamycin, acarbose, dasatinib, quercetin, curcumin, astaxanthin and arbutin;

(b) a pharmaceutically acceptable carrier or excipient.

Images