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Application of RORa protein and agonist thereof in preparation of anti-aging drugs

An anti-aging and agonist technology, applied in the field of biomedicine, can solve problems such as doubts about efficacy and safety, lack of anti-aging targets, and complex components of anti-aging drugs

Active Publication Date: 2022-08-05
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The present invention intends to provide the application of RORa protein and its agonist in the preparation of anti-aging drugs, so as to solve the technical problems of lack of existing anti-aging targets, complex components of anti-aging drugs, and doubtful efficacy and safety

Method used

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  • Application of RORa protein and agonist thereof in preparation of anti-aging drugs
  • Application of RORa protein and agonist thereof in preparation of anti-aging drugs
  • Application of RORa protein and agonist thereof in preparation of anti-aging drugs

Examples

Experimental program
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Effect test

Embodiment 1

[0070] The cholesterol sulfate compound (Cholesteryl sulfate, CS for short) used in this scheme is specifically cholesterol sulfate sodium salt (CAS: 2864-50-8), and the molecular formula is shown in formula (I). The main antibody information used in this protocol is as follows: Cdc42 antibody (Santa Cruz, RRID: AB_631213), α-Tubulin (Cell Signaling, RRID: AB_2567774), Cy3 goat anti-rabbit IgG (Jackson, RRID: AB_2338000), Alexa Fluor goat anti-rabbit IgG (Jackson, RRID: AB_2338046), phosphorylated H2AX antibody (Cell Signaling, RRID: AB_2118009).

[0071]

[0072] (1) Preparation of CS solution: CS was dissolved in DMSO to prepare a CS stock solution with a concentration of 50 mg / ml. CS working solution is formed by diluting CS stock solution to 5 mg / ml. CS working solution was used to prepare the test agent (injection) of CS group, and its components were: CS working solution 100 μL, Tween 80 20 μL and PBS 880 μL (PBS is conventional phosphate buffered saline solution in ...

experiment example 1

[0080] The mouse HSCs prepared in Example 1 were used for the detection of this experimental example, as follows:

[0081] 1. Immunofluorescence detection of cell polarity-related markers (Cdc42 and tubulin)

[0082] The polarity of cells means that the two ends of cells (groups) have different shapes or functions. With the progress of cell senescence, cell polarity gradually disappears. Studies have shown that Cdc42 (cyclin 42 in cell division) and tubulin (Tublin) in HSCs are important markers of cell polarity (Cdc42 Activity Regulates Hematopoietic Stem Cell Aging and Rejuvenation, Maria Carolina Florian, Cell Stem Cell 10, 520–530, May 4 , 2012). The highly asymmetric localization of Cdc42 and tubulin is not related to the substrate binding sites flanking the cell, nor is it related to the uneven distribution throughout the cytoplasm, but is the key to causing changes in cell polarity, which can affect and reflect cellular senescence status. In normal mouse HSCs, Cdc42 ...

experiment example 2

[0093] Experimental example 2: Immunofluorescence detection of RORa protein

[0094] 8-12-week-old mice were selected as young mice, and 18-month-old mice were selected as old mice for experiments. Except that the mice used in the experiment have been changed, other experimental settings and experimental procedures are shown in Example 1. After the experiment, the blood stem cells of the mice were taken for immunofluorescence experiments. For the experimental results, see Figure 16 (yHSCs represent young mice) and Figure 17 (oHSCs represent aged mice). Figure 16 and Figure 17 Among them, the image on the left is a representative cell image, and the image on the right is the statistical graph of the fluorescence intensity of about 80 cells in each treatment, and the average value (data format is mean ± SD, using T test P value to judge significance). The experimental results showed that the expression of RORa protein was up-regulated when CS was used to treat young and ...

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Abstract

The invention relates to the field of biological medicine, relates to an anti-aging drug, and in particular relates to application of RORa protein and an agonist thereof in preparation of the anti-aging drug. RORa is activated to promote DNA repair of senescence cells, so that DNA damage caused by senescence is reduced; in addition, the cell polarity of the blood stem cells is recovered by activating RORa, and the cell senescence phenotype is reversed. In the scheme, the anti-aging effect is achieved by activating RORa, and the function and mechanism are clear. According to the scheme, RORa protein agonists including cholesterol sulfate salt are mainly applied to activate the RORa protein, the cholesterol sulfate salt is simple in component, clear in action mechanism, safe and effective, the defects of anti-aging drugs such as plant extracts or traditional Chinese medicine compound extracts in the prior art are overcome, and good application prospects are achieved.

Description

technical field [0001] The invention relates to the field of biomedicine, relates to anti-aging drugs, in particular to the application of RORa protein and its agonist in preparing anti-aging drugs. Background technique [0002] Body aging has always been a hotspot in biological research. Aging is a process of continuous decline in the function of biological organisms or organs. Aging is a continuous and progressive process characterized by progressive weakening or loss of function at the molecular, cellular, tissue and body levels. Later in an organism's life cycle, biological senescence leads to decreased reproductive capacity and increased mortality with age. Senescence is the inevitable result of the differentiation and development of all multicellular organisms from germ cells to somatic cells. Body senescence and cellular senescence complement each other. Cellular senescence is manifested by permanent cell cycle arrest, impaired organelle accumulation, and a longer...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61K45/06A61K31/575A61P39/06
CPCA61K38/1783A61K45/06A61K31/575A61P39/06Y02A50/30
Inventor 李宁王楠邱焕迪何巍邱强高珩寒尹月霞王勃川
Owner SICHUAN UNIV
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