p53 maintains healthy aging [P53KO_PTENKO_RNAseq]

As a tumor suppressor, the antagonistic pleiotropy (AP) theory predicts a beneficial cancer suppression function for p53 early in life that becomes detrimental late in life, for example by promoting accumulation of senescent cells, an inflammatory cell fate driven by tumor suppressors and linked to age-associated disease.

Although p53 signaling is generally activated in aging and disease, p53 is also known to suppress some phenotypes of cellular senescence, and the function of p53 in aged tissues, as well as its causal role in aging, is not well-defined. Here we show, contrary to the prediction of AP, that p53 promotes healthy aging in mice by suppressing inflammation and maintaining metabolic function. Multimodal RNA, protein, epigenetic, and spatial profiling at the single-cell level in aged mouse liver confirmed the expected age-dependent increase of immune infiltration, accumulation of senescent cells, and p53 pathway activation.