Cellular Senescence in the Aging Kidney – Fight Aging!

The study of age-related diseases often focuses on changes in gene expression, but it’s crucial to also examine alterations in cell behavior. Researchers have linked PAR2 expression in the kidney to cellular senescence, a process where senescent cells accumulate with age, leading to chronic inflammation and tissue dysfunction. Understanding this connection can help in developing strategies to remove or prevent these senescent cells.

Cellular senescence plays a role in inflammatory kidney disease through the secretion of inflammatory and profibrotic factors. Protease-activating receptor 2 (PAR2) is known to regulate inflammation in kidney diseases, and this study uncovers its role in cellular senescence. The research shows that PAR2-induced metabolic changes in renal cells lead to senescence and increased inflammatory responses.

Experiments in vitro and in aging models demonstrate that PAR2 expression is linked to cellular senescence, and activation of PAR2 induces senescence in kidney epithelial cells. Senescent cells exhibit impaired fatty acid oxidation (FAO), highlighting the importance of FAO in senescence. Mice lacking PAR2 show protection against renal fibrosis and injury, with reduced senescence and inflammation. These findings suggest that targeting PAR2 or FAO could be a promising approach for managing kidney injury.

Link: https://doi.org/10.1111/acel.14184