Running on empty

How p53 controls INS/IGF signaling and affects life span

Heidi Scrable, Silvia Medrano, Erica Ungewitter

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

In higher organisms dependent on the regenerative ability of tissue stem cells to maintain tissue integrity throughout adulthood, the failure of stem cells to replace worn out, dead, or damaged cells is seen as one mechanism that limits life span. In these organisms, tumor suppressors such as p53 are central participants in the control of longevity because they regulate stem cell proliferation. Several recent reports have identified p53 as a longevity gene in organisms such as Caenorhabditis elegans and Drosophila melanogaster, which lack proliferative stem cells in all but the germline and have relatively short life spans. This has forced us to reevaluate the role of p53 in the control of life span. We discuss how p53 might regulate longevity in both long- and short-lived species by controlling the activity of insulin-like molecules that operate in proliferating and non-proliferating compartments of adult somatic tissues. We also discuss the hierarchical structure of life span regulation where loss of p53 has life span extending effects. Finally, we suggest a molecular mechanism by which p53 might facilitate the response to severe nutrient deprivation that allows metabolically active cells to survive periods of starvation. Paradoxically, loss of p53 function in these cells would compromise life span.

Original languageEnglish (US)
Pages (from-to)93-100
Number of pages8
JournalExperimental Gerontology
Volume44
Issue number1-2
DOIs
StatePublished - Jan 2009
Externally publishedYes

Fingerprint

Stem cells
Stem Cells
Tissue
Cell proliferation
Nutrients
Tumors
Genes
Caenorhabditis elegans
Insulin
Starvation
Drosophila melanogaster
Molecules
Cell Proliferation
Food
Neoplasms

Keywords

  • Caenorhabditis elegans
  • Drosophila
  • Metabolism
  • Neurons
  • Stem cells

ASJC Scopus subject areas

  • Aging
  • Biochemistry
  • Cell Biology
  • Endocrinology
  • Genetics
  • Molecular Biology

Cite this

Running on empty : How p53 controls INS/IGF signaling and affects life span. / Scrable, Heidi; Medrano, Silvia; Ungewitter, Erica.

In: Experimental Gerontology, Vol. 44, No. 1-2, 01.2009, p. 93-100.

Research output: Contribution to journalArticle

Scrable, Heidi ; Medrano, Silvia ; Ungewitter, Erica. / Running on empty : How p53 controls INS/IGF signaling and affects life span. In: Experimental Gerontology. 2009 ; Vol. 44, No. 1-2. pp. 93-100.
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