Innovative Treatment for Reducing Senescence and Revitalizing Aging Cells through Gene Silencing

Many studies explore whether harnessing a cellular state known as senescence holds the solution to revitalizing aging tissues. Senescent cells are unique in that they stop cell division but are resistant to apoptosis, a programmed cell death. Senescent cells continue to release chemicals that can trigger inflammation. mTOR inhibitors are currently the only known pharmacological interventions that increase lifespan and revitalize aging tissues in animal models. However, the side effect profiles of mTOR inhibitors are a major cause of concern because mTOR inhibitors inhibit the genes that regulate cell proliferation and immune cell differentiation. To explore a possible solution to the side effects of an mTOR inhibitor, we specifically targeted two mTOR downstream genes, RPS6KB1 (G1 cell cycle inducer) and PPARGC1A (mitochondria energy metabolism regulator) using a small interfering RNA (siRNA) to inhibit gene expression. We hypothesized that inhibiting expression of RPS6KB1 and PPARGC1A would decrease senescence caused by hydrogen peroxide (H2O2). We used human skin cells (Detroit 551) to test our hypothesis and induced senescence by H2O2 treatment. Our result indicates that when both genes were knocked down by siRNA on Detroit 551 cells pretreated with H2O2, the number of senescent cells significantly decreased compared to scrambled siRNA transfected control cells. Our results suggest that inhibiting gene expression of both RPS6KB1 and PPARGC1A may inhibit senescence. Our results may support the development of novel treatments for revitalizing aging tissues and inhibiting inflammation triggered by senescent cells.