The Regulation of Aging and Longevity: A New and Complex Role of p53

Abstract

Abstractp53 plays a critical role in tumor suppression. As a transcription factor, in response to stress signals, p53 regulates its target genes and initiates stress responses, including cell cycle arrest, apoptosis, and/or senescence, to exert its function in tumor suppression. Emerging evidence has suggested that p53 is also an important but complex player in the regulation of aging and longevity in worms, flies, mice, and humans. Whereas p53 accelerates the aging process and shortens life span in some contexts, p53 can also extend life span in some other contexts. Thus, p53 appears to regulate aging and longevity in a context-dependent manner. Here, the authors review some recent advances in the study of the role of p53 in the regulation of aging and longevity in both invertebrate and vertebrate models. Furthermore, they discuss the potential mechanisms by which p53 regulates aging and longevity, including the p53 regulation of insulin/TOR signaling, stem/progenitor cells, and reactive oxygen species.

Fucoxanthin increases lifespan of Drosophila melanogaster and Caenorhabditis elegans

“…However, in general the impact of the p53 gene expression on lifespan of different organisms is cell environmental properties dependent [69]. For example, the decrease of the CEP-1 gene expression (orthologue of p53 in C. elegans) can increase or decrease the worms' lifespan depending on the level of mitochondrial bioenergetic stress [70].…”

Expanding the p53 regulatory network: LncRNAs take up the challenge

“…For instance, basal p53 activity is involved in the control of stem cell renewal as p53 can limit the self-renewal of adult neural stem cells [14], regulate quiescence in hematopoietic stem cells [15], or block the reprograming of differentiated cells to induced pluripotent state (IPS) [16]. Nonetheless, several other processes are regulated by the basal levels of p53 [17,18], including the regulation of longevity and aging, as shown in worms and flies where the loss of p53 can be associated to increased longevity [19,20].…”

Human Periosteal Derived Stem Cell Potential: The Impact of age

“…Several potential processes have been proposed, including the regulation of the insulin/insulinlike growth factor, mTOR pathway, stem cells, and oxidative stress and reactive oxygen species. For instance, constitutive p53 activation may lead to the decline of self-renewal function of stem/progenitor cells and therefore contribute to aging [44], moreover its activation affects mTOR pathway, which drives conversion of "young" cells to senescent phenotype [45]. P53 levels increase with age, mirroring cumulative levels of stress [46], and inhibition of p53 results in an extension of fibroblast lifespan and osteoblastic differentiation [47].…”