Nature Genetics36, 1275 - 1281 (2004)
Published online: 21 November 2004; | doi:10.1038/ng1476
Insulin regulation of heart function in aging fruit flies
Robert J Wessells1, Erin Fitzgerald1, James R Cypser2, Marc Tatar2
& Rolf Bodmer1
1
The Burnham Institute, Center for Neuroscience and Aging, 10901 Torrey Pines Road, La Jolla, California 92037, USA.
2
Department of Ecology and Evolutionary Biology, Box G-W, Brown University, Providence, Rhode Island 02912, USA.
Correspondence should be addressed to Rolf Bodmer rolf@burnham.org
Insulin-IGF receptor (InR) signaling has a conserved role in regulating lifespan, but little is known about the genetic control of declining organ function. Here, we describe progressive changes of heart function in aging fruit flies: from one to seven weeks of a fly's age, the resting heart rate decreases and the rate of stress-induced heart failure increases. These age-related changes are minimized or absent in long-lived flies when systemic levels of insulin-like peptides are reduced and by mutations of the only receptor, InR, or its substrate, chico. Moreover, interfering with InR signaling exclusively in the heart, by overexpressing the phosphatase dPTEN or the forkhead transcription factor dFOXO, prevents the decline in cardiac performance with age. Thus, insulin-IGF signaling influences age-dependent organ physiology and senescence directly and autonomously, in addition to its systemic effect on lifespan. The aging fly heart is a model for studying the genetics of age-sensitive organ-specific pathology.
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