Targeting Senescent Cells: from Single-Cell Analysis to Therapeutics

Cellular senescence is observed in various kinds of cells as a result of repeating proliferation or exposure to various genotoxic stresses. It is also known that senescent cells can accumulate in organs as aging and become a substrate of age-related disorders. A novel therapeutic strategy that eliminates senescent cells specifically from the body, so-called “lysis of senescent cells (senolysis)” has been demonstrated to ameliorate various age-related diseases and extend the lifespan of mammals without increasing cancer incidence. Our group has recently identified senescence-associated molecules through omics studies and developed “senolytic vaccine” targeting Glycoprotein nonmetastatic melanoma protein B (GPNMB) as an antigen upregulated in senescent endothelial cells. GPNMB-vaccine could exhibit senolysis leading to amelioration of atherosclerosis and diabetes as well as aged-phenotype in mice.