Dataset Information

Chronic circadian misalignment accelerates immune senescence and abbreviates lifespan in mice.

ABSTRACT: Modern society characterized by a 24/7 lifestyle leads to misalignment between environmental cycles and endogenous circadian rhythms. Persisting circadian misalignment leads to deleterious effects on health and healthspan. However, the underlying mechanism remains not fully understood. Here, we subjected adult, wild-type mice to distinct chronic jet-lag paradigms, which showed that long-term circadian misalignment induced significant early mortality. Non-biased RNA sequencing analysis using liver and kidney showed marked activation of gene regulatory pathways associated with the immune system and immune disease in both organs. In accordance, we observed enhanced steatohepatitis with infiltration of inflammatory cells. The investigation of senescence-associated immune cell subsets from the spleens and mesenteric lymph nodes revealed an increase in PD-1⁺CD44^high CD4 T cells as well as CD95⁺GL7⁺ germinal center B cells, indicating that the long-term circadian misalignment exacerbates immune senescence and consequent chronic inflammation. Our results underscore immune homeostasis as a pivotal interventional target against clock-related disorders.

SUBMITTER: Inokawa H

PROVIDER: S-EPMC7018741 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Chronic circadian misalignment accelerates immune senescence and abbreviates lifespan in mice.

Inokawa Hitoshi H Umemura Yasuhiro Y Shimba Akihiro A Kawakami Eiryo E Koike Nobuya N Tsuchiya Yoshiki Y Ohashi Munehiro M Minami Yoichi Y Cui Guangwei G Asahi Takuma T Ono Ryutaro R Sasawaki Yuh Y Konishi Eiichi E Yoo Seung-Hee SH Chen Zheng Z Teramukai Satoshi S Ikuta Koichi K Yagita Kazuhiro K

Scientific reports 20200213 1

Modern society characterized by a 24/7 lifestyle leads to misalignment between environmental cycles and endogenous circadian rhythms. Persisting circadian misalignment leads to deleterious effects on health and healthspan. However, the underlying mechanism remains not fully understood. Here, we subjected adult, wild-type mice to distinct chronic jet-lag paradigms, which showed that long-term circadian misalignment induced significant early mortality. Non-biased RNA sequencing analysis using live ...[more]

PMID: 32054990

Similar Datasets

Project description:BackgroundCircadian clocks are found in nearly all organisms, from bacteria to mammals, and ensure that behavioral and physiological processes occur at optimal times of day and in the correct temporal order. It is becoming increasingly clear that chronic circadian misalignment (CCM), such as occurs in shift workers or as a result of aberrant sleeping and eating schedules common to modern society, has profound metabolic and cognitive consequences, but the proximate mechanisms connecting CCM with reduced organismal health are unknown. Furthermore, it has been difficult to disentangle whether the health effects are directly induced by misalignment or are secondary to the alterations in sleep and activity levels that commonly occur with CCM. Here, we investigated the consequences of CCM in the powerful model system of the fruit fly, Drosophila melanogaster. We subjected flies to daily 4-h phase delays in the light-dark schedule and used the Drosophila Activity Monitoring (DAM) system to continuously track locomotor activity and sleep while simultaneously monitoring fly lifespan.ResultsConsistent with previous results, we find that exposing flies to CCM leads to a ~ 15% reduction in median lifespan in both male and female flies. Importantly, we demonstrate that the reduced longevity occurs independent of changes in overall sleep or activity. To uncover potential molecular mechanisms of CCM-induced reduction in lifespan, we conducted whole body RNA-sequencing to assess differences in gene transcription between control and misaligned flies. CCM caused progressive, large-scale changes in gene expression characterized by upregulation of genes involved in response to toxic substances, aging and oxidative stress, and downregulation of genes involved in regulation of development and differentiation, gene expression and biosynthesis.ConclusionsMany of these gene expression changes mimic those that occur during natural aging, consistent with the idea that CCM results in premature organismal decline, however, we found that genes involved in lipid metabolism are overrepresented among those that are differentially regulated by CCM and aging. This category of genes is also among the earliest to exhibit CCM-induced changes in expression, thus highlighting altered lipid metabolism as a potentially important mediator of the negative health consequences of CCM.

Dataset Information

Chronic circadian misalignment accelerates immune senescence and abbreviates lifespan in mice.

Publications

Chronic circadian misalignment accelerates immune senescence and abbreviates lifespan in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets