# p21 (CDKN1A)

p21, encoded by the CDKN1A gene (cyclin-dependent kinase inhibitor 1A), is a strong brake on the cell cycle. It blocks cyclin-CDK complexes, especially CDK2. That enforces a cell-cycle arrest in the G1 and S phases, in response to p53 activation, DNA damage, and other stresses on your cells. By halting replication in a damaged cell, p21 buys time for repair. If the damage cannot be fixed, sustained p21 can lock in the senescent state. p21 levels rise with age in many tissues. So its level is used as one biomarker of senescent-cell burden. But p21 is not exclusive to senescence, and its induction can be context-dependent. Genetic experiments in mice show that tuning CDKN1A pushes cancer susceptibility and tissue health in opposite directions. That underscores its context-dependent biology.

## Sources

- El-Deiry WS, Tokino T, Velculescu VE, et al.. (1993). WAF1, a potential mediator of p53 tumor suppression. Cell. https://doi.org/10.1016/0092-8674(93)90500-P
- Noda A, Ning Y, Venable SF, Pereira-Smith OM, Smith JR. (1994). Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. Experimental Cell Research. https://doi.org/10.1006/excr.1994.1063

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_Canonical: https://longevity-switzerland.com/en/glossary/p21-cdkn1a · Part of Longevity Cities · Updated 2026-06-22_