Dietary restriction and the transcription factor clock delay eye aging to extend lifespan in Drosophila Melanogaster

Brian A. Hodge (), Geoffrey T. Meyerhof, Subhash D. Katewa, Ting Lian, Charles Lau, Sudipta Bar, Nicole Y. Leung, Menglin Li, David Li-Kroeger, Simon Melov, Birgit Schilling, Craig Montell and Pankaj Kapahi ()
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Brian A. Hodge: Buck Institute for Research on Aging
Geoffrey T. Meyerhof: Buck Institute for Research on Aging
Subhash D. Katewa: Buck Institute for Research on Aging
Ting Lian: Buck Institute for Research on Aging
Charles Lau: Buck Institute for Research on Aging
Sudipta Bar: Buck Institute for Research on Aging
Nicole Y. Leung: University of California, Santa Barbara
Menglin Li: University of California, Santa Barbara
David Li-Kroeger: Baylor College of Medicine
Simon Melov: Buck Institute for Research on Aging
Birgit Schilling: Buck Institute for Research on Aging
Craig Montell: University of California, Santa Barbara
Pankaj Kapahi: Buck Institute for Research on Aging

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Many vital processes in the eye are under circadian regulation, and circadian dysfunction has emerged as a potential driver of eye aging. Dietary restriction is one of the most robust lifespan-extending therapies and amplifies circadian rhythms with age. Herein, we demonstrate that dietary restriction extends lifespan in Drosophila melanogaster by promoting circadian homeostatic processes that protect the visual system from age- and light-associated damage. Altering the positive limb core molecular clock transcription factor, CLOCK, or CLOCK-output genes, accelerates visual senescence, induces a systemic immune response, and shortens lifespan. Flies subjected to dietary restriction are protected from the lifespan-shortening effects of photoreceptor activation. Inversely, photoreceptor inactivation, achieved via mutating rhodopsin or housing flies in constant darkness, primarily extends the lifespan of flies reared on a high-nutrient diet. Our findings establish the eye as a diet-sensitive modulator of lifespan and indicates that vision is an antagonistically pleiotropic process that contributes to organismal aging.

Date: 2022
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DOI: 10.1038/s41467-022-30975-4

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