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Cell biology

p16INK4a

p16INK4a is a brake on the cell cycle (a cyclin-dependent kinase inhibitor), made from the CDKN2A locus. It blocks CDK4/6, which halts the cell cycle and locks the cell into senescence. Its level climbs sharply with your chronological age across many tissues. That makes it a widely used marker of how many senescent cells you carry, and of biological aging. Selectively killing off p16-positive senescent cells (a process called senolysis) extends healthspan in mice. That is a big reason senolytic drugs are now in active development for age-related disease.

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Sources

  1. Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW. (1997). Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. *Cell*doi:10.1016/S0092-8674(00)81902-9
  2. Ressler S, Bartkova J, Niederegger H, et al.. (2006). p16INK4A is a robust in vivo biomarker of cellular aging in human skin. *Aging Cell*doi:10.1111/j.1474-9726.2006.00231.x
  3. Baker DJ, Wijshake T, Tchkonia T, et al.. (2011). Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. *Nature*doi:10.1038/nature10600