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Circadian autophagy drives iTRF-mediated longevity
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Journal Article
Circadian autophagy drives iTRF-mediated longevity
2021
Overview
Time-restricted feeding (TRF) has recently gained interest as a potential anti-ageing treatment for organisms from
Drosophila
to humans
1
–
5
. TRF restricts food intake to specific hours of the day. Because TRF controls the timing of feeding, rather than nutrient or caloric content, TRF has been hypothesized to depend on circadian-regulated functions; the underlying molecular mechanisms of its effects remain unclear. Here, to exploit the genetic tools and well-characterized ageing markers of
Drosophila
, we developed an intermittent TRF (iTRF) dietary regimen that robustly extended fly lifespan and delayed the onset of ageing markers in the muscles and gut. We found that iTRF enhanced circadian-regulated transcription and that iTRF-mediated lifespan extension required both circadian regulation and autophagy, a conserved longevity pathway. Night-specific induction of autophagy was both necessary and sufficient to extend lifespan on an ad libitum diet and also prevented further iTRF-mediated lifespan extension. By contrast, day-specific induction of autophagy did not extend lifespan. Thus, these results identify circadian-regulated autophagy as a critical contributor to iTRF-mediated health benefits in
Drosophila
. Because both circadian regulation and autophagy are highly conserved processes in human ageing, this work highlights the possibility that behavioural or pharmaceutical interventions that stimulate circadian-regulated autophagy might provide people with similar health benefits, such as delayed ageing and lifespan extension.
Circadian-regulated autophagy contributes to the health benefits of intermittent time-restricted feeding in
Drosophila
.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 14/19
/ 14/35
/ 38/89
/ 64/24
/ 82/1
/ 82/29
/ 82/51
/ 82/80
/ Aging
/ Animals
/ Circadian Clocks - radiation effects
/ Circadian Rhythm - physiology
/ Circadian Rhythm - radiation effects
/ Climbing
/ Darkness
/ Diet
/ Drosophila melanogaster - genetics
/ Drosophila melanogaster - physiology
/ Drosophila melanogaster - radiation effects
/ Feeding Behavior - physiology
/ Feeding Behavior - radiation effects
/ Female
/ Food
/ Humanities and Social Sciences
/ Insects
/ Insulin
/ Longevity - radiation effects
/ Male
/ Markers
/ Methods
/ Muscles
/ Proteins
/ Science
