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Age-related circadian disorganization caused by sympathetic dysfunction in peripheral clock regulation

The ability of the circadian clock to adapt to environmental changes is critical for maintaining homeostasis, preventing disease, and limiting the detrimental effects of aging. To date, little is known about age-related changes in the entrainment of peripheral clocks to external cues. We therefore e...

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Autores principales: Tahara, Yu, Takatsu, Yuta, Shiraishi, Takuya, Kikuchi, Yosuke, Yamazaki, Mayu, Motohashi, Hiroaki, Muto, Aya, Sasaki, Hiroyuki, Haraguchi, Atsushi, Kuriki, Daisuke, Nakamura, Takahiro J, Shibata, Shigenobu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515066/
https://www.ncbi.nlm.nih.gov/pubmed/28721279
http://dx.doi.org/10.1038/npjamd.2016.30
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author Tahara, Yu
Takatsu, Yuta
Shiraishi, Takuya
Kikuchi, Yosuke
Yamazaki, Mayu
Motohashi, Hiroaki
Muto, Aya
Sasaki, Hiroyuki
Haraguchi, Atsushi
Kuriki, Daisuke
Nakamura, Takahiro J
Shibata, Shigenobu
author_facet Tahara, Yu
Takatsu, Yuta
Shiraishi, Takuya
Kikuchi, Yosuke
Yamazaki, Mayu
Motohashi, Hiroaki
Muto, Aya
Sasaki, Hiroyuki
Haraguchi, Atsushi
Kuriki, Daisuke
Nakamura, Takahiro J
Shibata, Shigenobu
author_sort Tahara, Yu
collection PubMed
description The ability of the circadian clock to adapt to environmental changes is critical for maintaining homeostasis, preventing disease, and limiting the detrimental effects of aging. To date, little is known about age-related changes in the entrainment of peripheral clocks to external cues. We therefore evaluated the ability of the peripheral clocks of the kidney, liver, and submandibular gland to be entrained by external stimuli including light, food, stress, and exercise in young versus aged mice using in vivo bioluminescence monitoring. Despite a decline in locomotor activity, peripheral clocks in aged mice exhibited normal oscillation amplitudes under light–dark, constant darkness, and simulated jet lag conditions, with some abnormal phase alterations. However, age-related impairments were observed in peripheral clock entrainment to stress and exercise stimuli. Conversely, age-related enhancements were observed in peripheral clock entrainment to food stimuli and in the display of food anticipatory behaviors. Finally, we evaluated the hypothesis that deficits in sympathetic input from the central clock located in the suprachiasmatic nucleus of the hypothalamus were in part responsible for age-related differences in the entrainment. Aged animals showed an attenuated entrainment response to noradrenergic stimulation as well as decreased adrenergic receptor mRNA expression in target peripheral organs. Taken together, the present findings indicate that age-related circadian disorganization in entrainment to light, stress, and exercise is due to sympathetic dysfunctions in peripheral organs, while meal timing produces effective entrainment of aged peripheral circadian clocks.
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spelling pubmed-55150662017-07-18 Age-related circadian disorganization caused by sympathetic dysfunction in peripheral clock regulation Tahara, Yu Takatsu, Yuta Shiraishi, Takuya Kikuchi, Yosuke Yamazaki, Mayu Motohashi, Hiroaki Muto, Aya Sasaki, Hiroyuki Haraguchi, Atsushi Kuriki, Daisuke Nakamura, Takahiro J Shibata, Shigenobu NPJ Aging Mech Dis Article The ability of the circadian clock to adapt to environmental changes is critical for maintaining homeostasis, preventing disease, and limiting the detrimental effects of aging. To date, little is known about age-related changes in the entrainment of peripheral clocks to external cues. We therefore evaluated the ability of the peripheral clocks of the kidney, liver, and submandibular gland to be entrained by external stimuli including light, food, stress, and exercise in young versus aged mice using in vivo bioluminescence monitoring. Despite a decline in locomotor activity, peripheral clocks in aged mice exhibited normal oscillation amplitudes under light–dark, constant darkness, and simulated jet lag conditions, with some abnormal phase alterations. However, age-related impairments were observed in peripheral clock entrainment to stress and exercise stimuli. Conversely, age-related enhancements were observed in peripheral clock entrainment to food stimuli and in the display of food anticipatory behaviors. Finally, we evaluated the hypothesis that deficits in sympathetic input from the central clock located in the suprachiasmatic nucleus of the hypothalamus were in part responsible for age-related differences in the entrainment. Aged animals showed an attenuated entrainment response to noradrenergic stimulation as well as decreased adrenergic receptor mRNA expression in target peripheral organs. Taken together, the present findings indicate that age-related circadian disorganization in entrainment to light, stress, and exercise is due to sympathetic dysfunctions in peripheral organs, while meal timing produces effective entrainment of aged peripheral circadian clocks. Nature Publishing Group 2017-01-05 /pmc/articles/PMC5515066/ /pubmed/28721279 http://dx.doi.org/10.1038/npjamd.2016.30 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Tahara, Yu
Takatsu, Yuta
Shiraishi, Takuya
Kikuchi, Yosuke
Yamazaki, Mayu
Motohashi, Hiroaki
Muto, Aya
Sasaki, Hiroyuki
Haraguchi, Atsushi
Kuriki, Daisuke
Nakamura, Takahiro J
Shibata, Shigenobu
Age-related circadian disorganization caused by sympathetic dysfunction in peripheral clock regulation
title Age-related circadian disorganization caused by sympathetic dysfunction in peripheral clock regulation
title_full Age-related circadian disorganization caused by sympathetic dysfunction in peripheral clock regulation
title_fullStr Age-related circadian disorganization caused by sympathetic dysfunction in peripheral clock regulation
title_full_unstemmed Age-related circadian disorganization caused by sympathetic dysfunction in peripheral clock regulation
title_short Age-related circadian disorganization caused by sympathetic dysfunction in peripheral clock regulation
title_sort age-related circadian disorganization caused by sympathetic dysfunction in peripheral clock regulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515066/
https://www.ncbi.nlm.nih.gov/pubmed/28721279
http://dx.doi.org/10.1038/npjamd.2016.30
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