2021/01/15
The University of Tokyo
Kyushu University
Niigata University
Keio University School of Medicine
National Center for Geriatrics and Gerontology
Japan Agency for Medical Research and Development (AMED)
It is known that when cells are exposed to various stresses, they are induced to become senescent cells, which exhibit irreversible growth arrest. It has been previously shown that senescent cells accumulate in the body with aging and that genetically removing senescent cells from aged mice significantly delays the onset of age-associated diseases, such as arteriosclerosis and kidney damage, while also extending healthy lifespan. However, as it is known that senescent cells exhibit diversity depending on the tissue or organ, the development of drugs to eliminate these diverse senescent cells and the identification of their targets had not yet been achieved.
A research group led by Assistant Professor Yoshikazu Johmura and Professor Makoto Nakanishi of the Division of Cancer Cell Biology at The Institute of Medical Science, The University of Tokyo, has established a new method for the pure culture of senescent cells. Through screening, they searched for a group of genes essential for the survival of senescent cells and identified GLS1, which is involved in glutamine metabolism.
Through expression analysis of GLS1, they also revealed that in senescent cells, damage to the lysosomal membrane and a resulting decrease in intracellular pH increase their sensitivity to GLS1 inhibition. Furthermore, when a GLS1 inhibitor was administered to aged mice, senescent cells in various tissues and organs were eliminated, and aging phenomena were significantly ameliorated.
In addition, by examining the effects of the GLS1 inhibitor on various mouse models of age-related diseases, the research group also found it to be effective in ameliorating the symptoms of obesity-induced diabetes, arteriosclerosis, and non-alcoholic steatohepatitis (NASH).
These research findings have revealed the metabolic specificity of senescent cells and their resulting vulnerabilities. It is expected that the development of drugs targeting these characteristics will not only lead to an extension of healthy lifespan but also to the prevention and treatment of various age-associated diseases such as cancer and arteriosclerosis.
The results of this research were published in the American international scientific journal "Science" on January 15, 2021 (U.S. Eastern Time).
For the full press release, please see below.