| Aging is an inescapable part of the life process.Theories about the onset of aging vary considerably,and researchers have proposed more than 20 different theories since the experiments of the 19 th century.Current research suggests that aging may be the result of a combination of degenerative DNA damage,active aging-related genes,stem cell exhaustion,personal diet,and mental conditions,and no unified theoretical theory has yet been formulated.A comprehensive understanding of the mechanisms of aging,research on methods to slow down aging,and prevention of aging-related diseases are crucial to improving the quality of human life.DNA damage plays an essential role in the process of aging,and the accumulation of DNA damage can lead to cellular senescence or apoptosis.Previous studies have demonstrated that DNA double-strand breaks lead to cellular genomic rearrangements that activate the cellular DNA damage response,inducing a senescence-associated secretory phenotype and ultimately leading to the onset of tissue cell senescence.Recombinant adeno-associated virus vector is a vector that can be artificially transgenic by using natural adeno-associated virus modified by genetic engineering.It is widely used in various clinical gene therapy experiments due to its advantages of low immunogenicity,good safety,high transgenic efficiency and wide range of infected hosts.Mysm1 is an enzyme that deubiquitinates histone H2 A,which has a crucial role in hematopoietic function,cell and tissue development and differentiation,immune system maturation,immune regulation,and inflammatory factor secretion.There has been little research on the role of Mysm1 in aging.In this study,we experimentally demonstrated that Mysm1 is a key suppressor of aging as well as aging-related pathologies.As first observed,Mysm1 knockout mice live shorter lives and show significant signs of senescence compared to wild-type mice.Several senescence assay experiments were performed in order to confirm that Mysm1 knockout mice undergo senescence.As a result of the experiment,it was shown that Mysm1 plays an important role in senescence.There were varying degrees of aging-related damage in tissues and organs of Mysm1 knockout mice,and reduced Mysm1 expression was observed in MEF cell of mice with induced senescence,thus demonstrating the importance of Mysm1 expression in aging.As a result of deletion of Mysm1,senescence-related pathway proteins were expressed more,secretory phenotypes were accelerated,and the aging process was accelerated.In subsequent studies of Mysm1 deletion induced senescence,it was discovered that DNA damage played an important role.During the senescence process,DNA damage accumulation is a primary factor,and the DNA damage response leads to apoptosis and cellular senescence.The results of chemical staining of DNA damage marker proteins in mouse tissues and organs indicated more severe DNA damage in Mysm1 knockout mice.As determined by cellular assays,deletion of Mysm1 resulted in an accumulation of DNA damage in MEF cell of mice.Mysm1 was found to promote DNA repair and thus reduce the accumulation of DNA damage in further DNA damage repair experiments.Using AAV9-Mysm1 recombinant adeno-associated virus,we overexpressed Mysm1 in mice via intraperitoneal injection to examine the role Mysm1 plays in aging and aging-related diseases.Mice whose Mysm1 overexpression delayed aging and extended lifespan showed a decrease in the secretion of senescence-related substances.It was found that overexpression of Mysm1 delayed aging and improved the aging microenvironment.In summary,we found that Mysm1 is one of the key suppressor of aging as well as aging-related diseases.Mysm1 decelerates cellular senescence and the aging process by promoting DNA repair and reducing DNA damage accumulation.Mysm1 deficiency promotes the aging process and shortens the lifespan of mice,while overexpression of Mysm1 decelerates the aging process,improves the aging microenvironment,and reduces the damage caused by aging.Mysm1 may serve as a potential therapeutic target for the prevention of aging and aging-related diseases. |
PDF Full Text Request