09 October 2020

A living model of cellular aging

Cellular aging is a state of stopping the cell cycle due to loss of the ability to divide. It plays a key role in age-related organ dysfunction and age-related diseases, as well as in cancer, but the pathogenesis in vivo is largely unclear.

A research team led by Professor Makoto Nakanishi from the Institute of Medical Sciences of the University of Tokyo has created a mouse model that allows to characterize in vivo senescent (aging) cells that express the protein p16INK4a (p16high cells) involved in stopping the cell cycle and preventing division.

In the mouse model p16-Cre ERT2-tdTomato p16high cells were labeled with the red fluorescent protein tdTomato in vivo by tamoxifen administration to characterize their location and behavior.

Researchers have shown that tdTomato-positive (red) p16high cells are found in all organs, and with age there are more of them. They also noted that these cells could not proliferate and had a half–life of 2.6 to 4.2 months - depending on the tissue under study.


RNA sequencing of liver and kidney cells showed that p16high cells are present in various types of tissues, but predominate in the liver endothelium and in the epithelium of the proximal and distal tubules of the kidneys. These cells exhibit heterogeneous phenotypes associated with aging. In addition, the elimination of p16high cells reduced the manifestations of non-alcoholic steatohepatitis (NASH) – lipidosis and infiltration of immune cells. This is an interesting result from the point of view of prevention and treatment of NASH.

Thus, the new mouse model and analysis of individual cells provide a powerful resource for detecting previously unidentified aging functions in vivo. This is the first study in the world demonstrating the full profile of transcriptomes of individual senescent cells in vivo, and, perhaps, it will contribute to further elucidation of the causes of human aging and the development of anti-aging therapies.

Article by S.Omori et al. Generation of a p16 Reporter Mouse and Its Use to Characterize and Target p16high Cells In Vivo is published in the journal Cell Metabolism.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Tokyo: The world's first successful identification and characterization of in vivo senescent cells.

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