Gene
TP53 (p53)
Last updated 2026-07-02· Last reviewed 2026-07-02· 1 min read
Reviewed by the Ultimate Longevity Bible editorial team. Educational reference — not medical advice. See disclaimer.
Function
- Sensor: activated by DNA damage, hypoxia, oncogene expression, ribosomal stress.
- Effector: transcribes genes driving G1/S arrest (p21), DNA repair, senescence, or apoptosis (PUMA, BAX).
- Guardian: prevents propagation of damaged cells.
Longevity relevance
- Cancer suppression vs aging acceleration trade-off: hyperactive p53 (like the mouse p53+/m allele) reduces cancer but accelerates aging by depleting stem-cell pools.
- Species comparisons: African elephants carry ~20 copies of TP53 vs 1 in most mammals, contributing to Peto's paradox resolution.
- Somatic mosaicism: p53-inactivating mutations accumulate in ageing tissues, sometimes clonally expanding (particularly haematopoiesis).
Interventions
- MDM2 inhibitors (idasanutlin, KRT-232) activate p53 pharmacologically; approved uses are oncologic.
- Rapamycin and calorie restriction indirectly modulate p53 signalling via mTOR and AMPK crosstalk.
- CDKN1A (p21) — Gene.
- Rapamycin vs Senolytics — Comparison.
- Senomorphic — Concept.
- Senomorphic vs Senolytic — Concept.
- Senotherapeutic — Concept.