Reference Report

Reference
Citation	Wessells, R.J., Fitzgerald, E., Cypser, J.R., Tatar, M., Bodmer, R. (2004). Insulin regulation of heart function in aging fruit flies. Nat. Genet. 36(12): 1275--1281. (Export to RIS)
FlyBase ID	FBrf0184189
Publication Type	Research paper
PubMed ID	15565107
PubMed Abstract	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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Language of Publication	English
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Publication Type	Journal
Abbreviation	Nat. Genet.
Title	Nature Genetics
Publication Year	1992-
ISBN/ISSN	1061-4036 1546-1718
Data from Reference
Alleles (14)
	Avic\GFP^Scer\UAS.cUa chico¹ foxo^Scer\UAS.cFa foxo^TM.Scer\UAS InR²¹¹ InR²⁴⁶ InR²⁶² InR^E19 InR^Scer\UAS.cHa Pten^Scer\UAS.cGb rpr^Scer\UAS.C Scer\GAL4^Ilp2.PR Scer\GAL4^Scer\UAS.cHa Scer\GAL4^tin.cBa
Constructs (7)
	P{tin-Gal4.B} P{UAS-foxo.F} P{UAS-foxo.TM} P{UAS-Gal4.H} P{UAS-GFP.U} P{UAS-InR.H} P{UAS-rpr.C}
Genes (7)
	Avic\GFP chico foxo InR Pten rpr Scer\GAL4
Insertions (1)
	P{ry11}chico¹