Old flies have a robust central oscillator but weaker behavioral rhythms that can be improved by genetic and environmental manipulations

Aging Cell

Wenyu Luo¹  Wen-Feng Chen²  Zhifeng Yue²  Dechun Chen³  Mallory Sowcik²  Amita Sehgal² 

[1] Cell and Molecular Biology Program;Howard Hughes Medical Institute;Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

关键词: aging;    behavioral rhythms;    circadian clock;    period;    protein kinase A;    sleep;   

DOI  :  10.1111/j.1474-9726.2012.00800.x

来源: Wiley

【 摘 要 】

Summary

Sleep–wake cycles break down with age, but the causes of this degeneration are not clear. Using a Drosophila model, we addressed the contribution of circadian mechanisms to this age-induced deterioration. We found that in old flies, free-running circadian rhythms (behavioral rhythms assayed in constant darkness) have a longer period and an unstable phase before they eventually degenerate. Surprisingly, rhythms are weaker in light–dark cycles and the circadian-regulated morning peak of activity is diminished under these conditions. On a molecular level, aging results in reduced amplitude of circadian clock gene expression in peripheral tissues. However, oscillations of the clock protein PERIOD (PER) are robust and synchronized among different clock neurons, even in very old, arrhythmic flies. To improve rhythms in old flies, we manipulated environmental conditions, which can have direct effects on behavior, and also tested a role for molecules that act downstream of the clock. Coupling temperature cycles with a light–dark schedule or reducing expression of protein kinase A (PKA) improved behavioral rhythms and consolidated sleep. Our data demonstrate that a robust molecular timekeeping mechanism persists in the central pacemaker of aged flies, and reducing PKA can strengthen behavioral rhythms.

【 授权许可】

Unknown   
© 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland