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Application of Baz2b gene as target spot in senescence alleviation

A technology of aging and encoding genes, which is applied in the fields of genetic engineering, medical preparations containing active ingredients, compound screening, etc., and can solve problems such as unclear regulatory mechanisms

Active Publication Date: 2020-08-07
CENT FOR EXCELLENCE IN BRAIN SCI & INTELLIGENCE TECH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Changes in gene expression levels during brain aging may be due to changes in epigenetic modifications, but the specific regulatory mechanisms and how changes in the expression of these genes lead to behavioral degradation are not clear

Method used

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  • Application of Baz2b gene as target spot in senescence alleviation
  • Application of Baz2b gene as target spot in senescence alleviation
  • Application of Baz2b gene as target spot in senescence alleviation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0103] The expression situation of embodiment 1, Baz2b gene

[0104]Baz2b gene expression range is very broad, expressed in bone marrow, lung and brain and other tissues. By analyzing the databases GSE1572 and GSE44772 of human brain gene expression, the inventors found that the expression level of the Baz2b gene in the cerebral anterior cortex gradually increased with age ( figure 1 A).

[0105] Further analysis of the gene expression database in the prefrontal cortex of AD patients and normal elderly people found that the expression of Baz2b gene was significantly increased in AD patients compared with normal elderly people of the same age ( figure 1 B).

[0106] By analyzing the expression changes of Baz2b gene during the development of AD disease, the results showed that the expression level of Baz2b was significantly positively correlated with the late-onset AD disease process such as Braakst stage and the degree of precortical atrophy ( figure 1 C, D).

[0107] These...

Embodiment 2

[0108] Example 2, Baz2b knockout can improve the learning ability of aging animals

[0109] In order to explore the regulatory role of the Baz2b gene in aging, the inventors used the CRISPR / Cas9 method to construct Baz2b knockout mice.

[0110] For behavioral analyses, littermate Baz2b knockout heterozygous, homozygous, and wild-type mice were bred from Baz2b knockout heterozygous mice.

[0111] Analysis of Baz2b knockout heterozygous, homozygous, and wild-type mice during aging as they age. It was found that wild-type mice exhibited age-dependent weight gain, and the weights of Baz2b knockout heterozygous, homozygous and wild-type mice were not much different in the young stage ( figure 2 A, B), but the body weight of Baz2b knockout mice was significantly lower than that of wild-type mice in old age ( figure 2 A, B).

[0112] The spatial learning and memory ability of aged mice was detected by the Barnes maze test, and Baz2b knockout mice took less time to find the targe...

Embodiment 3

[0114] Example 3. Research on the Mechanism of Baz2b Improving the Function of Behavioral Degeneration in the Aging Process

[0115] Next, we explored the potential mechanism by which Baz2b functions to improve behavioral degradation during aging.

[0116] Since the Baz2b protein contains a DNA binding domain, the inventors detected which genes it bound to by chromatin immunoprecipitation quantitative PCR method. The results showed that Baz2b protein can bind to the promoter region of genes related to mitochondrial function ( Figure 4 A).

[0117] Treatment with shRNA (5'-GGCTCTTTCTCCAAGTTAA-3'(SEQ ID NO:3)) in the primary neurons of the cerebellum of mice showed that reducing the expression of Baz2b can increase the expression level of genes related to mitochondrial function ( Figure 4 B), thereby increasing the ATP level of neurons ( Figure 4 C), and the basal oxygen respiration of cells and the maximum oxygen respiration value induced by FCCP ( Figure 4 D).

[0118...

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Abstract

The invention relates to an application of a Baz2b gene as a target spot in senescence alleviation and discloses that the Baz2b gene plays an important role in regulating and controlling the occurrence and development of normal senescence and senescence-related diseases, and the down-adjustment of the Baz2b gene can obviously relieve senescence and improve memory degeneration, behavioral ability degeneration and the like in the senescence process. Therefore, the Baz2b can be used as a research target of senescence and senescence-related diseases, can be used for developing medicines for inhibiting or delaying senescence, and can be used as a marker for diagnosis and prognosis evaluation of senescence and senescence-related diseases.

Description

technical field [0001] The invention belongs to the field of biomedicine, and more specifically, the invention relates to the application of the Baz2b gene as a target in alleviating aging. Background technique [0002] The aging of the population in today's society is getting worse. According to the report of the World Health Organization, by 2050, one-third of the population in developing countries will be over 60 years old. During the aging process, the various physiological functions of the organism gradually decrease, such as the decline of cognitive ability and motor ability, the disturbance of sleep and rhythm, etc. (Bishop et al., 2010; Satoh et al., 2017); this will seriously affect the aging People's quality of life, but also a serious burden on society. In addition, aging is the most important risk factor for neurodegenerative diseases such as Alzheimer's disease (Lopez-Otin et al., 2013). Therefore, it will be very urgent to study the mechanisms of behavioral d...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6883G01N33/68A61K45/00A61P25/28A61P39/06
CPCC12Q1/6883G01N33/6893G01N33/6896A61K45/00A61P25/28A61P39/06G01N2800/28G01N2800/2814G01N2800/2821C12Q2600/158G01N2800/7042G01N33/6875G01N33/5023G01N2500/00C12N15/113A61K31/713C12N2310/20C12N2310/14C12N2310/531A01K67/0275A01K2217/075A01K2227/105A01K2267/03C12N15/11
Inventor 蔡时青袁洁常思源刘至洋
Owner CENT FOR EXCELLENCE IN BRAIN SCI & INTELLIGENCE TECH CHINESE ACAD OF SCI
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