. Author manuscript; available in PMC: 2020 Mar 30.

Published in final edited form as: Eur J Neurosci. 2018 Oct 30;51(1):454–481. doi: 10.1111/ejn.14176

Table 1:

Approaches for Reinforcement of the Circadian System in Aging Drosophila

Genetic rescue of circadian function
Gene	Problem	Manipulation	Outcome	Reference
pdf	Aging related reductions in circadian rhythmicity	Overexpression of pdf in clock neurons	Increased rhythmicity, restoration of TIM levels in older flies	Umezaki et al., 2012
per	Increased neurodegeneration in per⁰¹ flies	Rescue of per	Increased resistance to hypoxia and oxidative stress, reduction in neuronal degeneration	Krishnan et al., 2008
cry	Reduced cry mRNA expression and protein levels with aging	Overexpression of cry in all clock cells in the body	Increased resistance to oxidative stress. Increased rhythmicity and lifespan	Rakshit et al., 2013
tim	Age-related problems with metabolism	Overexpression of tim in peripheral tissues	Increased lifespan, metabolism and resistance to pathogens on a protein rich diet	Katewa et al., 2016
Environmental reinforcement of circadian clock
Paradigm	Problem	Manipulation	Outcome	Reference
Time restricted feeding	Reduced sleep in older flies and deterioration of cardiac function	Food restricted to 12 h/day during light cycle	Improved sleep/activity rhythms and decreased cardiac aging	Gill et al, 2015
Dietary Restriction	Reduced molecular rhythms of clock genes with aging	Ten days feeding with dietary restriction media	Increased molecular oscillations of core clock genes; extended lifespan	Katewa et al., 2016
Temperature entrainment	Disrupted sleep-wake rhythms with aging	Coupled entrainment of light and thermal cycles	Improved sleep and locomotor activity rhythms	Luo et al., 2012