Science · 2004 · 585 citations · 8 references
Life SciencesBiologyGeneticsAgingGene ExpressionSignal TransductionAdipose TissueAging PhysiologyBiological AgingGenetics Of AgingLongevityMetabolic SignalingAdipocyte Insulin SignalingFat Body AnatomyFoxo Transcription Factor RegulationFoxo Transcriptional RegulationInsulin Signaling Gene ExpressionInsulin Signaling PathwayInsulin-like SignalingReduced Fecundity
Reduced activity of the insulin/insulin-like growth factor signaling (IIS) pathway increases life-span in diverse organisms. We investigated the timing of the effect of reduced IIS on life-span and the role of a potential target tissue, the fat body. We overexpressed dFOXO, a downstream effector of IIS, in the adult Drosophila fat body, which increased life-span and reduced fecundity of females but had no effect on male life-span. The role of FOXO transcription factors and the adipose tissue are therefore evolutionarily conserved in the regulation of aging, and reduction of IIS in the adult is sufficient to mediate its effects on life-span and fecundity.
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Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor
Anne Brunet, Azad Bonni, Michael J. Zigmond et al. · Cell · 1999 · 6.6K citations · Full text
Extension of Life-Span by Loss of CHICO, a <i>Drosophila</i> Insulin Receptor Substrate Protein
David J. Clancy, David Gems, Lawrence G. Harshman et al. · Science · 2001 · 1.4K citations
Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue
Matthias Blüher, Barbara B. Kahn, C. Ronald Kahn · Science · 2003 · 1.4K citations
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