Authors: Curtis C; Landis GN; Folk D; Wehr NB; Hoe N; Waskar M; Abdueva D; Skvortsov D; Ford D; Luu A; Badrinath A; Levine RL; Bradley TJ; Tavaré S; Tower J
Abstract: BACKGROUND: Several interventions increase lifespan in model organisms, including reduced insulin/insulin-like growth factor-like signaling (IIS), FOXO transcription factor activation, dietary restriction, and superoxide dismutase (SOD) over-expression. One question is whether these manipulations function through different mechanisms, or whether they intersect on common processes affecting aging. RESULTS: A doxycycline-regulated system was used to over-express manganese-SOD (MnSOD) in adult Drosophila, yielding increases in mean and maximal lifespan of 20%. Increased lifespan resulted from lowered initial mortality rate and required MnSOD over-expression in the adult. Transcriptional profiling indicated that the expression of specific genes was altered by MnSOD in a manner opposite to their pattern during normal aging, revealing a set of candidate biomarkers of aging enriched for carbohydrate metabolism and electron transport genes and suggesting a true delay in physiological aging, rather than a novel phenotype. Strikingly, cross-dataset comparisons indicated that the pattern of gene expression caused by MnSOD was similar to that observed in long-lived Caenorhabditis elegans insulin-like signaling mutants and to the xenobiotic stress response, thus exposing potential conserved longevity promoting genes and implicating detoxification in Drosophila longevity. CONCLUSION: The data suggest that MnSOD up-regulation and a retrograde signal of reactive oxygen species from the mitochondria normally function as an intermediate step in the extension of lifespan caused by reduced insulin-like signaling in various species. The results implicate a species-conserved net of coordinated genes that affect the rate of senescence by modulating energetic efficiency, purine biosynthesis, apoptotic pathways, endocrine signals, and the detoxification and excretion of metabolites.
Keywords: Aging/*genetics; Animals; Animals, Genetically Modified; Carbohydrate Metabolism; Drosophila melanogaster/*physiology; Electron Transport; Female; *Gene Expression Profiling; Longevity; Male; Superoxide Dismutase/genetics/*physiology|
Journal: Genome biology Volume: 8 Issue: 12 Pages: R262 Date: Dec. 11, 2007 PMID: 18067683 |
Curtis C, Landis GN, Folk D, Wehr NB, Hoe N, Waskar M, Abdueva D, Skvortsov D, Ford D, Luu A, Badrinath A, Levine RL, Bradley TJ, Tavaré S, Tower J (2007) Transcriptional profiling of MnSOD-mediated lifespan extension in Drosophila reveals a species-general network of aging and metabolic genes. Genome biology 8: R262.
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