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 language | English (US) |
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Pages (from-to) | 245-248 |
Number of pages | 4 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 294 |
Issue number | 2 |
DOIs | |
State | Published - 2002 |
Externally published | Yes |
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology