Cells exhibiting strong <i>p16</i> ^<i>INK4a</i> promoter activation in vivo display features of senescence

Significance The accumulation of senescent cells over a lifetime causes age-related pathologies; however, the inability to reliably identify senescent cells in vivo has hindered clinical efforts to employ this knowledge as a means to ameliorate or reverse aging. Here, we describe a reporter allele, p16 tdTom , enabling the in vivo identification and isolation of cells featuring high-level activation of the p16 INK4a promoter. Our findings provide an insight into the functional and molecular characteristics of p16 INK4a -activated cells in vitro and in vivo. We show that such cells accumulate with aging or other models of injury, and that they exhibit clinically targetable features of cellular senescence(definition).