Cargando…

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

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 const...

Descripción completa

Detalles Bibliográficos
Autores principales: Luo, Wenyu, Chen, Wen-Feng, Yue, Zhifeng, Chen, Dechun, Sowcik, Mallory, Sehgal, Amita, Zheng, Xiangzhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353743/
https://www.ncbi.nlm.nih.gov/pubmed/22268765
http://dx.doi.org/10.1111/j.1474-9726.2012.00800.x
_version_ 1782233097900654592
author Luo, Wenyu
Chen, Wen-Feng
Yue, Zhifeng
Chen, Dechun
Sowcik, Mallory
Sehgal, Amita
Zheng, Xiangzhong
author_facet Luo, Wenyu
Chen, Wen-Feng
Yue, Zhifeng
Chen, Dechun
Sowcik, Mallory
Sehgal, Amita
Zheng, Xiangzhong
author_sort Luo, Wenyu
collection PubMed
description 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.
format Online
Article
Text
id pubmed-3353743
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Blackwell Publishing Ltd
record_format MEDLINE/PubMed
spelling pubmed-33537432012-12-01 Old flies have a robust central oscillator but weaker behavioral rhythms that can be improved by genetic and environmental manipulations Luo, Wenyu Chen, Wen-Feng Yue, Zhifeng Chen, Dechun Sowcik, Mallory Sehgal, Amita Zheng, Xiangzhong Aging Cell Original Articles 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. Blackwell Publishing Ltd 2012-06 /pmc/articles/PMC3353743/ /pubmed/22268765 http://dx.doi.org/10.1111/j.1474-9726.2012.00800.x Text en © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Original Articles
Luo, Wenyu
Chen, Wen-Feng
Yue, Zhifeng
Chen, Dechun
Sowcik, Mallory
Sehgal, Amita
Zheng, Xiangzhong
Old flies have a robust central oscillator but weaker behavioral rhythms that can be improved by genetic and environmental manipulations
title Old flies have a robust central oscillator but weaker behavioral rhythms that can be improved by genetic and environmental manipulations
title_full Old flies have a robust central oscillator but weaker behavioral rhythms that can be improved by genetic and environmental manipulations
title_fullStr Old flies have a robust central oscillator but weaker behavioral rhythms that can be improved by genetic and environmental manipulations
title_full_unstemmed Old flies have a robust central oscillator but weaker behavioral rhythms that can be improved by genetic and environmental manipulations
title_short Old flies have a robust central oscillator but weaker behavioral rhythms that can be improved by genetic and environmental manipulations
title_sort old flies have a robust central oscillator but weaker behavioral rhythms that can be improved by genetic and environmental manipulations
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353743/
https://www.ncbi.nlm.nih.gov/pubmed/22268765
http://dx.doi.org/10.1111/j.1474-9726.2012.00800.x
work_keys_str_mv AT luowenyu oldflieshavearobustcentraloscillatorbutweakerbehavioralrhythmsthatcanbeimprovedbygeneticandenvironmentalmanipulations
AT chenwenfeng oldflieshavearobustcentraloscillatorbutweakerbehavioralrhythmsthatcanbeimprovedbygeneticandenvironmentalmanipulations
AT yuezhifeng oldflieshavearobustcentraloscillatorbutweakerbehavioralrhythmsthatcanbeimprovedbygeneticandenvironmentalmanipulations
AT chendechun oldflieshavearobustcentraloscillatorbutweakerbehavioralrhythmsthatcanbeimprovedbygeneticandenvironmentalmanipulations
AT sowcikmallory oldflieshavearobustcentraloscillatorbutweakerbehavioralrhythmsthatcanbeimprovedbygeneticandenvironmentalmanipulations
AT sehgalamita oldflieshavearobustcentraloscillatorbutweakerbehavioralrhythmsthatcanbeimprovedbygeneticandenvironmentalmanipulations
AT zhengxiangzhong oldflieshavearobustcentraloscillatorbutweakerbehavioralrhythmsthatcanbeimprovedbygeneticandenvironmentalmanipulations