Modulation of Longevity and Tissue Homeostasis by the Drosophila PGC-1 Homolog

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. ► Upregulation of dPGC-1 increases mitochondrial gene expression and activity ► dPGC-1 modulates fuel homeostasis in the adult fly ► dPGC-1 protects against the age-related loss of intestinal homeostasis and integrity ► Upregulation of dPGC-1 in the digestive tract extends life span