Journal
CELL METABOLISM
Volume 14, Issue 5, Pages 623-634Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2011.09.013
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Funding
- Emerald Foundation
- G. Harold and Leila Y. Mathers Charitable Foundation
- American Cancer Society
- California Institute for Regenerative Medicine
- National Institutes of Health (NIH) [R01 AG028092, 2T32HD007495]
- Ruth L. Kirschstein National Research Service Award [GM07185]
- National Institute on Aging [R01 AG037514]
- Ellison Medical Foundation
- University of California, Los Angeles Older Americans Independence Center
- NIH/National Institute on Aging (NIA) [P30-AG028748]
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In mammals, the PGC-1 transcriptional coactivators are key regulators of energy metabolism, including mitochondrial biogenesis and respiration, which have been implicated in numerous pathogenic conditions, including neurodegeneration and cardiomyopathy. Here, we show that overexpression of the Drosophila PGC-1 homolog (dPGC-1/spargel) is sufficient to increase mitochondria! activity. Moreover, tissue-specific overexpression of dPGC-1 in stem and progenitor cells within the digestive tract extends life span. Long-lived flies overexpressing dPGC-1 display a delay in the onset of aging-related changes in the intestine, leading to improved tissue homeostasis in old flies. Together, these results demonstrate that dPGC-1 can slow aging both at the level of cellular changes in an individual tissue and also at the organismal level by extending life span. Our findings point to the possibility that alterations in PGC-1 activity in high-turnover tissues, such as the intestine, may be an important determinant of longevity in mammals.
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