Abstract

Cellular senescence is an important in vivo mechanism that prevents the propagation of damaged cells. Senescent cells undergo extensive metabolic and transcriptional changes, affecting their surrounding microenvironment. Activation of senescence during aging has been demonstrated to be detrimental. However, the precise mechanism(s) regulating senescence and aging and how senescence influences the tissue homeostasis is not well characterized. Here, we show a role for integrin beta 3 (β3) as a hallmark of cellular senescence and aging. β3 expression accelerates the onset of senescence in human primary fibroblasts by activating the TGF β pathway. ITGB3 is transcriptionally regulated during oncogene-induced senescence (OIS), causing an increase in the endogenous levels β3. Conversely, perturbation of β3 levels or activity overrides OIS . Finally, we show an increase in β3 levels during aging in mice and humans. Altogether, these results show a role for the integrin subunit, β3, during senescence.