p53 and a human premature ageing disorder

It has been shown that enhanced levels of p53 activity contribute to reduced cancer susceptibility in mice, however longevity is compromised due to the onset of an early-ageing phenotype. The effects of enhanced levels of p53 in these in mice could therefore have implications for human premature ageing disorders. We examined the DNA damage response of p53 and its target p21(WAF1) to UV and ionising radiation in fibroblasts from patients with the premature ageing disorder Hutchinson-Gilford Progeria (HGP). We report a normal p53 response to these DNA damaging agents suggesting that, in this particular human disorder, the premature ageing phenotype does not arise from an enhanced p53 response.