Abstract
Through its ability to evoke responses from cells in a paracrine fashion, the senescence-associated secretory phenotype (SASP) has been linked to numerous age-associated disease pathologies including tumor invasion, cardiovascular dysfunction, neuroinflammation, osteoarthritis, and renal disease. Strategies which limit the amplitude and duration of SASP serve to delay age-related degenerative decline. Here we demonstrate that the SASP regulation is linked to shifts in intracellular Ca(2+) homeostasis and strategies which rescue redox-dependent calcium entry including enzymatic H(2)O(2) scavenging, TRP modulation, or mTOR inhibition block SASP and TRPC6 gene expression. As Ca(2+) is indispensable for secretion from both secretory and non-secretory cells, it is exciting to speculate that the expression of plasma lamellar TRP channels critical for the maintenance of intracellular Ca(2+) homeostasis may be coordinately regulated with the SASP.