Insights into aging obtained from p53 mutant mouse models.

摘要: Cancer suppression is an integral component of longevity in organisms with renewable tissues. A number genes the mammalian genome function cancer prevention, and some these have been directly implicated assurance. One such assurance gene tumor suppressor p53, a transcription factor that mutated or dysregulated most human cancers. Early studies linked p53 to induction cellular senescence, whereas recent reports implicate it as potential regulator organismal aging. We shown by inactivation loss enhances susceptibility reduces mouse. serendipitously generated mutant allele resulted hypermorphic version displays increased resistance, yet also mediates decreased longevity. The reduced accompanied accelerated onset variety aging phenotypes. These include 20% decrease median life span, early osteoporosis, lordokyphosis, organ atrophy, delayed wound healing, regenerative response after various stresses. Since initial characterization mice, we attempted elucidate underlying molecular mechanisms could be influencing Molecular product indicate induces increase activity both vitro vivo contexts. age-associated cellularity tissue responses mice are consistent stem cell functional capacity. Our model enhanced growth inhibitory produces earlier ability cells produce adequate numbers progenitor mature differentiated each organ. Currently, performing assays from wild-type test this model. challenge for future will find ways manipulate provide still enhance overall