Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog.

Authors: Rera M; Bahadorani S; Cho J; Koehler CL; Ulgherait M; Hur JH; Ansari WS; Lo T Jr; Jones DL; Walker DW

Abstract: 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 mitochondrial 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.

Keywords: Animals; Cell Respiration; Drosophila Proteins/genetics/*metabolism; Drosophila melanogaster/genetics/*metabolism; Energy Metabolism/physiology; Female; Gene Expression/physiology; Glucose/metabolism; Homeostasis/physiology; Intestines/cytology/*metabolism; Longevity/*genetics; Male; Mammals; Mice; Mitochondria/genetics/*metabolism; Organ Specificity; Positive Transcriptional Elongation Factor B/genetics/*metabolism; Sequence Homology, Amino Acid; Stem Cells/cytology/metabolism; Transcription Factors/genetics/*metabolism
Journal: Cell metabolism
Volume: 14
Issue: 5
Pages: 623-34
Date: Nov. 8, 2011
PMID: 22055505
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Rera M, Bahadorani S, Cho J, Koehler CL, Ulgherait M, Hur JH, Ansari WS, Lo T Jr, Jones DL, Walker DW (2011) Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog. Cell metabolism 14: 623-34.

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