Transcriptional profiling of MnSOD-mediated lifespan extension in Drosophila reveals a species-general network of aging and metabolic genes.
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.


CONCLUSIONS
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.
Curtis
Christina
C
Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-1340, USA. ccurtis@usc.edu
Landis
Gary N
GN
Folk
Donna
D
Wehr
Nancy B
NB
Hoe
Nicholas
N
Waskar
Morris
M
Abdueva
Diana
D
Skvortsov
Dmitriy
D
Ford
Daniel
D
Luu
Allan
A
Badrinath
Ananth
A
Levine
Rodney L
RL
Bradley
Timothy J
TJ
Tavaré
Simon
S
Tower
John
J
D000375:Aging / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified; D050260:Carbohydrate Metabolism; D004331:Drosophila melanogaster / Q000502:physiology*; D004579:Electron Transport; D005260:Female; D020869:Gene Expression Profiling; D008136:Longevity; D008297:Male; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology*
D013482:Superoxide Dismutase