title: Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog.
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.
authors: Department of Integrative Biology and Physiology, University of California-Los Angeles, CA 90095, USA.
authors: Michael
authors: M
authors: Rera
authors: Sepehr
authors: S
authors: Bahadorani
authors: Jaehyoung
authors: J
authors: Cho
authors: Christopher L
authors: CL
authors: Koehler
authors: Matthew
authors: M
authors: Ulgherait
authors: Jae H
authors: JH
authors: Hur
authors: William S
authors: WS
authors: Ansari
authors: Thomas
authors: T
authors: Lo
authors: D Leanne
authors: DL
authors: Jones
authors: David W
authors: DW
authors: Walker
mesh_terms: D000818:Animals; D019069:Cell Respiration; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D008136:Longevity / Q000235:genetics*; D008297:Male; D008322:Mammals; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D042925:Positive Transcriptional Elongation Factor B / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; C527201:pgc protein, Drosophila; D042925:Positive Transcriptional Elongation Factor B; D005947:Glucose