Application of Chaetocin in Anti-aging

Abstract

The present invention relates to the technical field of anti-aging drugs, and in particular to the application of chaetocin in anti-aging. The present invention uses an aging cell model and an aging mouse model to screen and obtain a drug chaetocin (chaetocin) with anti-aging effects. After cell and mouse experiments, it was verified that chaetocin can not only effectively inhibit hair loss, weight loss, cardiac fibrosis, liver fibrosis, kidney fibrosis, spleen fibrosis, lung fibrosis, arterial adventitial fibrosis and smooth muscle loss, but also prolong life, increase abdominal fat, and relieve cardiac inflammation, kidney inflammation, liver inflammation, lung inflammation, spleen inflammation, small intestine inflammation and skin inflammation. The chaetocin provided by the present invention can be used as an anti-aging drug and applied to the research and development of drugs for treating a variety of aging-related diseases.

Description

Technical Field

[0001] The invention relates to the technical field of anti-aging drugs, and in particular to the application of chaetocin in anti-aging. Background Art

[0002] Hutchinson-Gilford progeria syndrome is an accelerated aging disease caused by a mutation in the gene LMNA. Typical symptoms of patients include hair loss, subcutaneous fat loss, osteoporosis, atherosclerosis, chronic inflammation, tissue and organ fibrosis, myocardial infarction, stroke, etc. The average life expectancy of patients with progeria is 14.5 years. Studies have found that 90% of patients with progeria contain a heterozygous mutation of c.1824C>T, which activates the alternative splicing site of the gene LMNA, leading to the production of the progerin protein. Recent studies have found that the progerin protein not only causes progeria, but is also expressed during normal aging. Therefore, progeria is a favorable tool for studying the mechanism of aging and developing anti-aging drugs. In 2020, the US FDA approved Zokinvy, the first drug for the treatment of progeria, which injected fresh blood into anti-aging drugs.

[0003] However, as a farnesyl transferase inhibitor, Zokinvy not only inhibits the farnesylation modification of the progerin protein, but also inhibits the post-translational modification of lamin A, lamin B1 / B2, Ras and other proteins. Therefore, it has significant side effects. Summary of the invention

[0004] In order to solve the problems existing in the prior art, the present invention provides the application of chaetocin in anti-aging.

[0005] The present invention screened out an anti-aging drug chaetocin through the GFP-progerin aging cell model, aging mouse model and anti-aging drug screening method established in the early stage, and verified its effectiveness at the cell level and mouse level.

[0006] In a first aspect, the present invention provides the use of chaetocin in anti-aging.

[0007] The present invention further provides the use of chaetocin in preparing anti-aging medicines.

[0008] Furthermore, the anti-aging includes any one or more of the following:

[0009] i) inhibiting one or more of hair loss, weight loss, cardiac fibrosis, liver fibrosis, kidney fibrosis, spleen fibrosis, lung fibrosis, adventitial fibrosis or smooth muscle loss;

[0010] ii) increase lifespan or increase abdominal fat;

[0011] iii) alleviating one or more of heart inflammation, kidney inflammation, liver inflammation, lung inflammation, spleen inflammation, small intestine inflammation or skin inflammation.

[0012] Furthermore, the anti-aging comprises:

[0013] Inhibit the expression of aging-related inflammatory factors in mice.

[0014] Furthermore, the inhibiting the expression of aging-related inflammatory factors in mice is inhibiting the expression of aging-related inflammatory factors in any one or more organs of the mouse's heart, liver, spleen, lung, kidney, small intestine and skin.

[0015] Furthermore, the aging-related inflammatory factors include:

[0016] One or more of IL1A, IL1B, IL6, IL8 or MMP3.

[0017] Furthermore, the anti-aging is to promote the transfer of progerin in cells from the nuclear membrane to the nucleus.

[0018] In a second aspect, the present invention provides a drug for anti-aging, wherein the drug comprises chaetocin.

[0019] Furthermore, the dosage of chaetocin in the medicine is 0.05-0.3 mg / kg.

[0020] Furthermore, the solvent of the drug includes DMSO, PEG300, Tween-80 and saline.

[0021] Furthermore, the mass ratio of DMSO, PEG300, Tween-80 and saline in the solvent is (8-12): (15-25): (3-7): (40-50).

[0022] Preferably, the mass ratio of DMSO, PEG300, Tween-80 and saline in the solvent is 10:20:5:45.

[0023] The present invention has the following beneficial effects:

[0024] The present invention uses the previously established GFP-progerin aging cell model and mouse model to screen and obtain an anti-aging drug chaetocin, and verifies its effectiveness at the cellular level and mouse level. It is found that it can effectively inhibit hair loss, weight loss, cardiac fibrosis, liver fibrosis, kidney fibrosis, spleen fibrosis, lung fibrosis, arterial adventitial fibrosis and smooth muscle loss, and can also prolong life, increase abdominal fat, and relieve cardiac inflammation, kidney inflammation, liver inflammation, lung inflammation, spleen inflammation, small intestinal inflammation and skin inflammation.

[0025] The chaetocin provided by the present invention is an anti-aging drug and can be used for the research and development of drugs for diseases such as premature aging, aging, hair loss, cardiovascular disease, osteoporosis, lipodystrophy, myocardial infarction, chronic inflammation, and tissue and organ fibrosis, and has important significance in the field of screening anti-aging drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is the dynamic observation result of living cells after chaetocin treatment provided in Example 1 of the present invention, wherein the green fluorescence represents the progerin GFP-progerin.

[0027] Figure 2 The chaetocin provided in Example 1 of the present invention causes the localization result of GFP-progerin in the cell nucleus; wherein the green fluorescence represents the progerin GFP-progerin, the red fluorescence represents the lamin B1, and the blue fluorescence represents the chromatin.

[0028] Figure 3 This is the result of the effect of chaetocin on the nuclear localization of GFP-progerin provided in Example 1 of the present invention.

[0029] Figure 4 This is the result of chaetocin inhibiting GFP-progerin aging cell nuclear membrane budding provided in Example 1 of the present invention; wherein, green fluorescence represents the progerin GFP-progerin, red fluorescence represents the nuclear lamin B1, and blue fluorescence represents chromatin.

[0030] Figure 5 This is the result of the effect of chaetocin on nuclear membrane budding in GFP-progerin senescent cells provided in Example 1 of the present invention.

[0031] Figure 6 This is the result of chaetocin inhibiting nuclear membrane budding in progeria patients provided in Example 1 of the present invention; wherein, green fluorescence represents progerin, red fluorescence represents lamin B1, and blue fluorescence represents chromatin.

[0032] Figure 7 This is the effect of chaetocin provided in Example 1 of the present invention on nuclear membrane budding in cells of progeria patients.

[0033] Figure 8 This is a photo of aging mice 3 months after administration provided in Example 1 of the present invention; wherein, the left side is the control group mice (Control), and the right side is the experimental group mice (Chaetocin).

[0034] Fig. 9 This is an anatomical diagram of aging mice after 3 months of drug administration provided in Example 1 of the present invention; wherein, the left side is the control group mice (Control), and the right side is the experimental group mice (Chaetocin).

[0035] Fig.10 This is the weight recording result of the aging mice provided in Example 1 of the present invention.

[0036] Fig.11 This is the survival curve result of aging mice provided in Example 1 of the present invention.

[0037] Fig.12 The heart artery slice results of aged mice after 3 months of drug administration provided in Example 1 of the present invention; wherein, the upper part is the control group mice (Control), and the lower part is the experimental group mice (Chaetocin).

[0038] Fig.13 This is the statistical result of the thickness of the cardiac arteries of aged mice after 3 months of drug administration provided in Example 1 of the present invention.

[0039] Fig.14 The heart slice results of aged mice after 3 months of drug administration provided in Example 1 of the present invention; wherein, the upper part is the control group mice (Control), and the lower part is the experimental group mice (Chaetocin).

[0040] Fig.15 This is the statistical result of the cardiac fibrosis area ratio of aged mice after 3 months of administration provided in Example 1 of the present invention.

[0041] Fig.16 The liver slice results of aged mice after 3 months of drug administration provided in Example 1 of the present invention; wherein, the upper part is the control group mice (Control), and the lower part is the experimental group mice (Chaetocin).

[0042] Fig.17 The statistical results of the liver fibrosis area ratio of aged mice after 3 months of administration provided in Example 1 of the present invention.

[0043] Fig.18The kidney slice results of aged mice after 3 months of drug administration provided in Example 1 of the present invention; wherein, the upper part is the control group mice (Control), and the lower part is the experimental group mice (Chaetocin).

[0044] Fig.19 The statistical results of the renal fibrosis area ratio of aged mice after 3 months of administration provided in Example 1 of the present invention.

[0045] Fig. 20 The spleen slice results of aged mice after 3 months of drug administration provided in Example 1 of the present invention; wherein, the upper part is the control group mice (Control), and the lower part is the experimental group mice (Chaetocin).

[0046] Fig.21 The statistical results of the spleen fibrosis area ratio of aged mice after 3 months of administration provided in Example 1 of the present invention.

[0047] Fig. 22 The lung slice results of aged mice after 3 months of drug administration provided in Example 1 of the present invention; wherein, the upper part is the control group mice (Control), and the lower part is the experimental group mice (Chaetocin).

[0048] Fig.23 The statistical results of the proportion of lung fibrosis area in aged mice after 3 months of administration provided in Example 1 of the present invention.

[0049] Fig.24 This is the expression result of cardiac inflammatory factors in aged mice after 3 months of administration provided in Example 1 of the present invention.

[0050] Fig.25 This is the result of the expression of inflammatory factors in the liver of aged mice after 3 months of administration provided in Example 1 of the present invention.

[0051] Fig.26 This is the expression result of inflammatory factors in the spleen of aged mice after 3 months of administration provided in Example 1 of the present invention.

[0052] Fig. 27 This is the result of the expression of pulmonary inflammatory factors in aged mice 3 months after administration provided in Example 1 of the present invention.

[0053] Fig.28 The results of renal inflammatory factor expression in aged mice 3 months after administration provided in Example 1 of the present invention.

[0054] Fig.29 These are the results of expression of inflammatory factors in the small intestine of aged mice after 3 months of administration as provided in Example 1 of the present invention.

[0055] Fig.30The results of skin inflammatory factor expression in aged mice 3 months after administration provided in Example 1 of the present invention. DETAILED DESCRIPTION

[0056] The following examples are used to illustrate the present invention but are not intended to limit the scope of the present invention.

[0057] Example 1

[0058] 1. The GFP-progerin senescent cell model used in the present invention is obtained by overexpressing the progerin protein in primary human skin fibroblasts using a lentiviral vector. The coding sequence of the progerin protein is shown in SEQ ID NO.1.

[0059] 2. The present invention screened a drug chaetocin with anti-aging effect based on the GFP-progerin senescent cell model, and verified its anti-aging effect by cells and mice. The specific process is as follows:

[0060] 2.1 Cell verification process:

[0061] 2.1.1 Treatment of cells

[0062] Senescent cells were subcultured into 35 mm dynamic culture dishes and 35 mm ordinary culture dishes covered with coverslips, and 3 ml of culture medium was added for culture. When the cell density reached 60-80%, 10 nM-200 nM chaetocin was used for treatment for 12-48 hours.

[0063] Culture medium: high glucose Dulbecco's modified Eagle medium (DMEM) + 5-20% fetal bovine serum + 100 U / mL penicillin + 100 μg / mL streptomycin.

[0064] 2.1.2 Cell Observation

[0065] The treated dynamic culture dish was placed under a confocal microscope for dynamic observation of live cells and video was taken. The ordinary culture medium covered with a coverslip was used for cell immunofluorescence observation and the proportion of abnormal cell nuclei was counted.

[0066] The procedure of cell immunofluorescence is as follows:

[0067] (1) Senescent cells (GFP-progerin senescent cells and senescent cells from patients with progeria) were passaged into a 35 mm culture dish covered with a coverslip, 3 ml of culture medium was added, and the dish was placed in a cell culture incubator containing 5% CO2 at 37°C;

[0068] (2) When the cell density reaches 60-80%, treat with 10 nM-200 nM chaetocin for 12-48 hours;

[0069] (3) The coverslips were washed three times with PBS and then fixed with 4% paraformaldehyde (PFA) for 20 min;

[0070] (4) After washing three times with PBS, the wells were perforated with 2.5% Triton-100 for 5 min;

[0071] (5) After washing with PBS three times, the fixed cells were labeled with antibodies. Antibodies against progerin and lamin B1 were added to 3% BSA in PBS buffer at a ratio of 1:200. The fixed cells were inverted in the primary antibody dilution solution and incubated overnight at 4°C.

[0072] (6) After incubation, the cells were gently washed three times in PBS buffer;

[0073] (7) According to the species of the primary antibody, the fluorescent secondary antibody was diluted in 3% BSA buffer at a ratio of 1:200, and the fixed cells were then incubated upside down in the secondary antibody dilution solution at room temperature for 1 hr.

[0074] (8) Heat Mowiol mounting medium containing 1 μg / mL DNA dye DAPI and 2.5% anti-quenching agent DABCO in a 55°C oven in advance. Wash the cells after secondary antibody incubation with PBS three times, then invert on 15 μL melted Mowiol mounting medium, dry at room temperature in the dark for 1 hour, and perform microscopic imaging after the mounting medium solidifies.

[0075] (9) Microscope imaging was performed using a DeltaVision microscope (equipped with an Olympus IX-71 inverted microscope, a 100× / 1.4NA oil objective lens, and a CCD camera); and images were processed using Volocity 6.1.1 software.

[0076] The results of cell immunofluorescence were Figure 1-Figure 7 As shown, Figure 1 The results showed that chaetocin treatment could cause GFP-progerin to form aggregates and localize in the nucleus away from the nuclear membrane. Figure 2-Figure 3 The results showed that compared with the control group (Control), chaetocin treatment could cause GFP-progerin to be localized in the cell nucleus. Figure 4-Figure 5 It was shown that chaetocin treatment could inhibit nuclear membrane budding of GFP-progerin senescent cells. Figure 6-Figure 7 It was shown that chaetocin treatment could inhibit nuclear membrane budding in progeria cells compared with the control group.

[0077] 2.2 Mouse Validation

[0078] 2.2.1 Drug administration to mice

[0079] lmna G609G / G609G Aged mice were divided into a control group (18 mice) and an experimental group (23 mice). They were given intraperitoneal injections starting at 4 weeks of age. The experimental group mice were given chaetocin at a dose of 0.1 mg / kg, with a solvent of 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline; the control group mice were given an equal volume of solvent. All mice were given the drug once every 3 days for 3 months.

[0080] 2.2.2 Record weight, take photos, and calculate survival rate

[0081] From lmna G609G / G609G The aged mice were weighed starting from 14 days after birth and every 3 days until the mice died. The mice were photographed 3 months after the drug administration. The death time of the mice was counted and the survival curve was drawn after summary.

[0082] The results are as follows Figure 8-Figure 11 As shown, Figure 8 The results show that chaetocin administration for 3 months can significantly improve the hair loss on the back of aged mice (indicated by arrows). This indicates that chaetocin can significantly inhibit hair loss in aged mice and has an anti-hair loss effect. Fig. 9 The results show that chaetocin administration for 3 months significantly increased the abdominal fat of aged mice (indicated by arrows), indicating that chaetocin can significantly improve lipodystrophy in aged mice. Fig.10 It was shown that chaetocin could significantly inhibit the weight loss of aging mice. Fig.11 The results showed that the average lifespan of mice in the control group (Control) was 140 days, and the median lifespan was 131 days; the average lifespan of mice in the experimental group (Chaetocin) was 172 months, and the median lifespan was 159 days. Chaetocin can extend the median lifespan of aged mice by 21.4% and the maximum lifespan by 20.4%, indicating that chaetocin can significantly extend the lifespan of aged mice.

[0083] 2.2.3 Pathological section analysis

[0084] In LMN aG609G / G609G After 3 months of drug administration, the aged mice were anesthetized and dissected. The fresh tissues were fixed and then paraffin-sectioned. The pathological conditions of blood vessels, liver, kidney, heart, spleen, lung, etc. were analyzed by H&E staining and Masson staining.

[0085] The process of paraffin sectioning is as follows:

[0086] (1) Take fresh tissue and fix it with fixative for more than 24 hours; then remove the tissue from the fixative, trim the target area with a scalpel in a fume hood, and place the trimmed tissue and corresponding labels in a dehydration box.

[0087] (2) Place the dehydration box in the dehydration machine and dehydrate with graded alcohols in sequence: 75% alcohol for 4 hours, 85% alcohol for 2 hours, 90% alcohol for 2 hours, 95% alcohol for 1 hour, anhydrous ethanol I for 30 minutes, anhydrous ethanol II for 30 minutes, alcohol benzene for 5-10 minutes, xylene I for 5-10 minutes, xylene II for 5-10 minutes, paraffin I melted at 65℃ for 1 hour, paraffin II melted at 65℃ for 1 hour, paraffin III melted at 65℃ for 1 hour.

[0088] (3) Embed the wax-soaked tissue in an embedding machine; first put the melted wax into the embedding frame, take the tissue out of the dehydration box before the wax solidifies, put it into the embedding frame according to the requirements of the embedding surface, and affix the corresponding label. Cool it in a -20℃ freezer, take the wax block out of the embedding frame after the wax solidifies, and trim the wax block.

[0089] (4) Place the trimmed wax block in a -20℃ freezer to cool, and then place the cooled wax block in a paraffin slicer to slice it to a thickness of 4μm. Float the slices on 40℃ warm water on the slicer to flatten the tissue, pick up the tissue with a slide, and bake the slices in a 60℃ oven. After the wax is baked dry, take it out and store it at room temperature for later use.

[0090] The H&E staining procedure is as follows:

[0091] (1) Sequentially place the sections in xylene I for 20 min, xylene II for 20 min, anhydrous ethanol I for 5 min, anhydrous ethanol II for 5 min, 75% alcohol for 5 min, and wash with tap water;

[0092] (2) Stain the sections with hematoxylin solution for 3-5 minutes, wash with tap water, differentiate with differentiation solution, wash with tap water, blue with bluing solution, and rinse with running water;

[0093] (3) Dehydrate the sections in 85% and 95% graded alcohol for 5 min each, and then stain them in eosin solution for 5 min.

[0094] (4) Place the sections in anhydrous ethanol I for 5 min, anhydrous ethanol II for 5 min, anhydrous ethanol III for 5 min, xylene I for 5 min, and xylene II for 5 min to make them transparent, and finally seal the sections with neutral gum;

[0095] (5) Perform microscopic examination and image acquisition and analysis; cell nuclei appear blue and cytoplasm appears red;

[0096] The masson staining procedure is as follows:

[0097] (1) Sequentially place the sections in xylene I for 20 min, xylene II for 20 min, anhydrous ethanol I for 5 min, anhydrous ethanol II for 5 min, 75% alcohol for 5 min, and wash with tap water;

[0098] (2) Soak the sections in Masson A solution overnight and then wash with tap water;

[0099] (3) Immerse the sections in a dye solution of Masson B and Masson C in equal proportions for 1 min, wash with tap water, differentiate with 1% hydrochloric acid alcohol, and wash with tap water;

[0100] (4) Immerse the sections in Masson D solution for 6 min and rinse with tap water;

[0101] (5) Immerse the slices in Masson E solution for 1 min;

[0102] (6) Without washing, drain slightly and directly put into Masson F solution for dyeing for 2-30 seconds;

[0103] (7) Rinse and differentiate the sections with 1% glacial acetic acid and dehydrate them with two cylinders of anhydrous ethanol;

[0104] (8) Place the slices in a third cylinder of anhydrous ethanol for 5 minutes, place them in xylene for 5 minutes to make them transparent, and seal them with neutral gum.

[0105] (9) Perform microscopic examination and image acquisition and analysis; collagen fibers appear blue; muscle fibers, cellulose, and red blood cells appear red;

[0106] The results are as follows Figure 12-Figure 23 As shown, Fig.12 The results showed that chaetocin can significantly inhibit adventitial fibrosis and alleviate the loss of arterial smooth muscle in aged mice after 3 months of administration. These results show that chaetocin can significantly improve vascular defects in aged mice and inhibit adventitial fibrosis and loss of arterial smooth muscle. Fig.13 It was shown that chaetocin could significantly inhibit vascular thickening in aged mice. Fig.14 It was shown that chaetocin administration for 3 months could significantly inhibit cardiac fibrosis in aged mice. Fig.15 The results showed that the cardiac fibrosis area ratio of the experimental group mice (Chaetocin) was significantly reduced compared with the control group mice (Control). This indicates that chaetocin can significantly inhibit cardiac fibrosis in aging mice. Fig.16 It was shown that chaetocin administration for 3 months could significantly inhibit liver fibrosis in aged mice. Fig.17The results showed that the proportion of liver fibrosis area in the experimental group (Chaetocin) was significantly reduced compared with the control group (Control), indicating that chaetocin can significantly inhibit liver fibrosis in aging mice. Fig.18 It was shown that chaetocin administration for 3 months could significantly inhibit renal fibrosis in aged mice. Fig.19 The results showed that the proportion of renal fibrosis area in the experimental group (Chaetocin) was significantly reduced compared with that in the control group (Control), indicating that chaetocin can significantly inhibit renal fibrosis in aging mice. Fig. 20 It was shown that chaetocin administration for 3 months could significantly inhibit spleen fibrosis in aged mice. Fig.21 The results showed that the proportion of spleen fibrosis area in the experimental group (Chaetocin) was significantly reduced compared with that in the control group (Control), indicating that chaetocin can significantly inhibit spleen fibrosis in aging mice. Fig. 22 It was shown that chaetocin administration for 3 months could significantly inhibit pulmonary fibrosis in aged mice. Fig.23 The results showed that the proportion of lung fibrosis area in the experimental group (Chaetocin) was significantly reduced compared with the control group (Control), indicating that chaetocin can significantly inhibit lung fibrosis in aging mice.

[0107] 2.2.4 Detection of inflammatory factors

[0108] Another typical feature of aging is the increase of aging-related secretory phenotypes; the present invention detects the expression of five marker genes of aging-related secretory phenotypes, IL1A, IL1B, IL6, IL8, and MMP3, by RT-PCR experiments. The specific operation is as follows:

[0109] (1) Take fresh mouse tissue, add appropriate amount of Trizol, and use a homogenizer to break the tissue;

[0110] (2) Extract total RNA according to the Trizol operating instructions;

[0111] (3) Total RNA was used for reverse transcription, and then fluorescence quantitative PCR was performed to detect the expression levels of five marker genes: IL1A, IL1B, IL6, IL8, and MMP3.

[0112] The sequences of the PCR primers used are as follows:

[0113] IL1A:5'-AGGAGAGCCGGGTGACAGTA-3',

[0114] 5'-TCAGAATCTTCCCGTTGCTTG-3';

[0115] IL1B:5'-CCAAAAGATGAAGGGCTGCT-3',

[0116] 5′-TCATCAGGACAGCCCAGGTC-3′;

[0117] IL6:5'-ACAACCACGGCCTTCCCTACTT-3',

[0118] 5'-CACGATTTCCCAGAGAACATGTG-3';

[0119] IL8:5'-CTGGTCCATGCTCCTGCTG-3',

[0120] 5′-GGACGGACGAAGATGCCTAG-3′;

[0121] MMP3:5'-TGGAGCTGATGCATAAGCCC-3',

[0122] 5′-TGAAGCCACCAACATCAGGA-3′.

[0123] The results are as follows Figure 24-Figure 30 As shown, Fig.24 Compared with the control group (Control), the hearts of the experimental group (Chaetocin) mice had low expression of IL1A, IL1B, IL6, IL8, and MMP3 aging-related inflammatory factors. This indicates that chaetocin can significantly inhibit cardiac inflammation in aging mice. Fig.25 Compared with the control group (Control), the liver of the experimental group (Chaetocin) mice had low expression of IL1A, IL1B, IL6, IL8, and MMP3 aging-related inflammatory factors. This indicates that chaetocin can significantly inhibit liver inflammation in aging mice. Fig.26 Compared with the control group (Control), the spleen of the experimental group (Chaetocin) mice had low expression of IL1A, IL1B, IL6, IL8, and MMP3 aging-related inflammatory factors. This indicates that chaetocin can significantly inhibit spleen inflammation in aging mice. Fig. 27 Compared with the control group (Control), the lungs of the experimental group (Chaetocin) mice had low expression of IL1A, IL1B, IL6, IL8, and MMP3 aging-related inflammatory factors. This indicates that chaetocin can significantly inhibit lung inflammation in aging mice. Fig.28Compared with the control group (Control), the kidneys of the experimental group (Chaetocin) mice had low expression of IL1A, IL1B, and IL6 aging-related inflammatory factors. This indicates that chaetocin can significantly inhibit renal inflammation in aging mice. Fig.29 The results showed that compared with the control group (Control), the small intestine of the experimental group (Chaetocin) mice had low expression of IL1A, IL1B, IL6, IL8, and MMP3 aging-related inflammatory factors. This indicates that chaetocin can significantly inhibit small intestinal inflammation in aging mice. Fig.30 The results showed that compared with the control group (Control), the skin of the experimental group (Chaetocin) mice had low expression of IL1A, IL1B, IL6, IL8, and MMP3 aging-related inflammatory factors. This indicates that chaetocin can significantly inhibit skin inflammation in aging mice.

[0124] Although the present invention has been described in detail above with general descriptions and specific embodiments, it is obvious to those skilled in the art that some modifications or improvements may be made thereto based on the present invention. Therefore, these modifications or improvements made without departing from the spirit of the present invention all fall within the scope of protection claimed by the present invention. Sequence Listing <110> Beijing University <120> Application of Chaetocin in Anti-aging <130> KHP221115880.8 <160> 1 <170> SIPOSequenceListing 1.0 <210> 1 <211> 1845 <212> DNA <213> Artificial Sequence <400> 1 atggagaccc cgtcccagcg gcgcgccacc cgcagcgggg cgcaggccag ctccactccg 60 ctgtcgccca cccgcatcac ccggctgcag gagaaggagg acctgcagga gctcaatgat 120 cgcttggcgg tctacatcga ccgtgtgcgc tcgctggaaa cggagaacgc agggctgcgc 180 cttcgcatca ccgagtctga agaggtggtc agccgcgagg tgtccggcat caaggccgcc 240 tacgaggccg agctcgggga tgcccgcaag acccttgact ggggccaa ggagcgcgcc 300 cgcctgcagc tggagctgag caaagtgcgt gaggattta aggagctgaa agcgcgcaat 360 accaagaagg agggtgacct gatagctgct caggctcggc tgaaggacct ggaggctctg 420 ctgaactcca aggaggccgc actgagcact gctctcagtg agaagcgcac gctggagggc 480 gagctgcatg atctgcgggg ccaggtggcc aagcttgagg cagccctagg tgaggccaag 540 aagcaacttc aggatgagat gctgcgggggg gtggatgctg agaacaggct gcagaccatg 600 aggaggaac tggacttcca gaagaacatc tacagtgagg agctgcgtga gaccaagcgc 660 cgtcatgaga cccgactggt ggagattgac aatgggaagc agcgtgagtt tgagagccgg 720 ctggcggatg cgctgcagga actgcgggcc cagcatgagg accaggtgga gcagtataag 780 aggagctgg agaagactta ttctgccaag ctggacaatg ccaggcagtc tgctgagagg 840 aacagcaacc tggtggggc tgcccacgag gagctgcagc agtcgcgcat ccgcatcgac 900 agcctctctg cccagctcag ccagctccag aagcagctgg cagccaagga ggcgaagctt 960 cgagacctgg aggactcact ggcccgtgag cgggacacca gccggcggct gctggcgga aaggagcggg agatggccga gatgcgggca aggatgcagc agcagctgga cgagtaccag 1080. gagcttctgg acatcaagct ggccctggac atggagatcc acgcctaccg caagctcttg gagggcgagg aggagaggct acgcctgtcc cccagcccta cctcgcagcg cagccgtggc 1200 cgtgcttcct ctcactcatc ccagacacag ggtgggggca gcgtcacca aaagcgcaaa ctggagtcca ctgagagccg cagcagcttc tcacagcacg cacgcactag cgggcgcgtg 1320. gccgtggagg aggtggatga ggagggcaag tttgtccggc tgcgcaacaa gtccaatgag 1380 gaccagtcca tgggcaattg gcagatcaag cgccagaatg gagatgatcc cttgctgact taccggttcc caccaaagtt caccctgaag gctgggcagg tggtgacgat ctgggctgca ggagctgggg ccacccacag cccccctacc gacctggtgt ggaggcaca gaacacctgg ggctgcggga acagcctgcg tacggctctc atcaactcca ctggggaaga agtggccatg 1620 cgcaagctgg tgcgctcagt gactgtggtt gaggacgacg aggatgagga tggagatgac 1680 ctgctccatc accaccacgg ctcccactgc agcagctcgg gggaccccgc tgagtacaac 1740 ctgcgctcgc gcaccgtgct gtgcgggacc tgcgggcagc ctgccgacaa ggcatctgcc agcggctcag gagcccagag cccccagac tgcagcatca tgtaa

Claims

1. Application of chaetocin in the preparation of anti-aging drugs; The anti-aging method is to promote the transfer of progerin in cells from the nuclear membrane to the nucleus, thereby reducing nuclear membrane budding. The anti-aging includes the following: i) inhibiting hair loss, weight loss, kidney fibrosis, spleen fibrosis, lung fibrosis, arterial adventitial fibrosis and smooth muscle loss; ii) Increased lifespan and increased abdominal fat; iii) Relieve inflammation of the heart, kidneys, liver, lungs, spleen, small intestine and skin.

2. The use according to claim 1, characterized in that: The anti-aging treatment includes: Inhibit the expression of aging-related inflammatory factors in mice.

3. The use according to claim 2, characterized in that: The method of inhibiting the expression of aging-related inflammatory factors in mice is to inhibit the expression of aging-related inflammatory factors in any one or more organs of the heart, liver, spleen, lung, kidney, small intestine and skin of the mice.

4. The use according to claim 2 or 3, characterized in that: The aging-related inflammatory factors include: One or more of IL1A, IL1B, IL6, IL8 or MMP3.

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