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+CD44high 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.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Inokawa H,Umemura Y,Shimba A,Kawakami E,Koike N,Tsuchiya Y,Ohashi M,Minami Y,Cui G,Asahi T,Ono R,Sasawaki Y,Konishi E,Yoo SH,Chen Z,Teramukai S,Ikuta K,Yagita Kdoi
10.1038/s41598-020-59541-ysubject
Has Abstractpub_date
2020-02-13 00:00:00pages
2569issue
1issn
2045-2322pii
10.1038/s41598-020-59541-yjournal_volume
10pub_type
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