A role for mitochondria as potential regulators of cellular life span

Dong Xu, Toren Finkel

Research output: Contribution to journalArticlepeer-review

Abstract

We demonstrate that by simply raising extracellular pyruvate levels, and hence increasing metabolic supply, human diploid fibroblasts undergo a concentration-dependent induction of cellular senescence. Fibroblasts treated with pyruvate undergo a rapid growth arrest accompanied by elevated levels of the cell-cycle regulatory molecules p53, p21, and p16. These cells also exhibit a rise in mitochondrial oxidant production and a fall in intracellular glutathione levels. Exposure of pyruvate treated cells to the antioxidant and glutathione precursor N-acetylcysteine restores cell growth and reverses the increase in senescence-associated β-galactosidase activity. Similarly, we demonstrate that by increasing mitochondrial number via retroviral-mediated expression of the mitochondrial biogenesis regulator PGC-1 there is also a reduction in cell growth and the more rapid induction of senescence. These results suggest that mitochondria appear to play a central role in regulating cellular life span.

Original languageEnglish (US)
Pages (from-to)245-248
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume294
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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