Application of histone deubiquitinase in preparation of medicines for resisting aging and treating aging-related diseases

A technology for deubiquitinating enzymes and histones, applied in the field of biomedicine, can solve problems such as mechanisms that have not been fully revealed

Pending Publication Date: 2021-02-09
吴建国
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Unfortunately, the mechanisms of aging have not been fully understood

Method used

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  • Application of histone deubiquitinase in preparation of medicines for resisting aging and treating aging-related diseases
  • Application of histone deubiquitinase in preparation of medicines for resisting aging and treating aging-related diseases
  • Application of histone deubiquitinase in preparation of medicines for resisting aging and treating aging-related diseases

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Experimental program
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Effect test

Embodiment 1

[0037] To determine the correlation between MYSM1 and age and aging, mouse sample analysis: take mice of different ages and detect the expression of MYSM1. Primary cell experiment: MEFs isolated from C57BL / 6 mice were used as a model and stimulated with the senescence inducer Etoposide (ETO) to detect the expression of MYSM1. Molecular and cell biology research: using senescence inducer etoposide (ETO) and hydrogen peroxide (Hydrogen peroxide, H 2 o 2 ), stimulated human embryonic lung fibroblasts (WI-38) and C57BL / 6 mouse primary embryonic fibroblasts (MEF), detected and analyzed the expression and secretion of immune factors, inflammatory factors, and aging-related molecules.

[0038] Specific steps are as follows:

[0039] (A–C) C57BL / 6 mouse MEFs were stimulated with etoposide (ETO) or doxorubicin hydrochloride (DOX) (A). Kidneys (B) and lungs (C) were obtained from 2-month-old and 22-month-old wild-type (WT) mice (n=3 per group). RT-PCR method was used to detect Mysm1...

Embodiment 2

[0042] Molecular mechanism of MYSM1 suppressing cellular senescence.

[0043] Determine the correlation between MYSM1 and DNA damage, mouse sample analysis: take mice of different ages, detect Mysm1 wild-type mice (C57BL / 6WT) and Mysm1 knockout mice (C57BL / 6Mysm1 - / - ) DNA damage signal expression. Primary cell experiment: MEFs isolated from C57BL / 6 mice were used as a model, stimulated with the senescence inducer etoposide, and the cell viability was detected. Detect the degree of DNA damage. Molecular and cell biology research: Human embryonic lung fibroblasts (WI-38) and C57BL / 6 mouse primary embryonic fibroblasts (MEF) were stimulated with senescence inducers etoposide and hydrogen peroxide to detect cell damage repair Systemic response, elucidating the mechanism of MYSM1 regulating injury.

[0044] The steps are: (A and B) wild-type (WT) or Mysm1 - / - MEFs were treated with DOX. Cytopathic Assay Cytotoxicity (A). Cell viability was determined with CCK8 kit. (C–E)WT ...

Embodiment 3

[0047] Knockout of MYSM1 leads to accelerated aging of the organism.

[0048] Using the C57BL / 6 mouse model, establish knockout mice similar to MYSM1, stimulate gene knockout mice with aging inducer etoposide and ionizing radiation, and study natural aging mice at the same time, detect and analyze immune factors and inflammatory factors in tissues and organs, The expression of aging-related molecules confirms the function of MYSM1 in regulating lifespan and tissue damage in mice. Take old mice, analyze the activation of immune pathways in tissues and organs in the natural aging model, and confirm the aging situation and the mechanism of organ damage. It is clear that knockout of MYSM1 promotes the aging of the body.

[0049] The steps are: (A–D) 10-month-old WT and Mysm1 - / - Image analysis of body (A), body (B), thorax (C) and head (D) of mice. (E) Analysis of 2-month-old WT and Mysm1 - / - Body length (cm) of mice (n=7 per group). (F)WT and Mysm1 - / - Mouse body weight ana...

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Abstract

The invention provides application of histone deubiquitinase in preparation of medicines for resisting aging and treating aging-related diseases, and relates to the technical field of biological medicines. The nucleotide sequence of the histone H2A deubiquitinase MYSM1 is shown as SEQ ID NO.1. Through verification, MYSM1 protein is deleted to cause remarkable aging of mice and induce aging-relateddiseases; and MYSM1 promotes DNA damage repair, blocks cell senescence and inhibits chronic inflammation. Adeno-associated viruses expressing murine MYSM1 are used as gene therapy results to prove that MYSM1 can significantly prolong the life of mice, reduce the process and quantity of aging cells, improve the normal functions of tissues and organs and reduce the occurrence and development of aging-related diseases; and it is proved that MYSM1 has good application prospects in delaying aging and treating aging-related diseases.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to the application of histone deubiquitinase in the preparation of medicines for anti-aging and treating aging-related diseases. Background technique [0002] Delaying Aging and Prolonging Lifespan have been people's eternal pursuit of dreams since ancient times. Aging is a common biological phenomenon during the growth and development of the body; the aging of the body is usually manifested in cell cycle disorder and excessive immune response and inflammatory response, leading to immune damage and dysfunction of tissues and organs, and severe degenerative diseases. Therefore, it is of great significance to study the molecular targets of anti-aging and their application in delaying aging and prolonging lifespan. [0003] There is a lot of evidence to support cellular senescence (Cellular Senescence) is an important factor in the development of aging and age-related d...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K38/48A61P39/06
CPCA61K48/005A61K48/0008A61K38/4813A61P39/06C12Y304/19A61K38/48C12N9/485C12N15/86A01K67/0275A01K2217/075A01K2227/105A01K2267/035C12N2750/14143A61K47/62A61K38/10A61K45/06
Inventor 吴建国田明富黄钰清邬开朗谭秋萍
Owner 吴建国
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