Defining the age-dependent and tissue-specific circadian transcriptome in male mice

Cellular circadian clocks direct a daily transcriptional program that supports homeostasis and resilience. Emerging evidence has demonstrated age-associated changes in circadian functions. To define age-dependent changes at the systems level, we profile the circadian transcriptome in the hypothalamu...

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Published in:	Cell reports (Cambridge) Vol. 42; no. 1; p. 111982
Main Authors:	Wolff, Christopher A., Gutierrez-Monreal, Miguel A., Meng, Lingsong, Zhang, Xiping, Douma, Lauren G., Costello, Hannah M., Douglas, Collin M., Ebrahimi, Elnaz, Pham, Ann, Oliveira, Aline C., Fu, Chunhua, Nguyen, Amy, Alava, Bryan R., Hesketh, Stuart J., Morris, Andrew R., Endale, Mehari M., Crislip, G. Ryan, Cheng, Kit-yan, Schroder, Elizabeth A., Delisle, Brian P., Bryant, Andrew J., Gumz, Michelle L., Huo, Zhiguang, Liu, Andrew C., Esser, Karyn A.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 31-01-2023 Elsevier
Subjects:	adrenal gland aging Aging - genetics Aging - metabolism Animals circadian clock Circadian Clocks - genetics Circadian Rhythm - genetics CP: Developmental biology CP: Molecular biology heart Hypothalamus kidney lung Male Mice RNA-seq skeletal muscle Transcriptome - genetics lung kidney RNA-seq CP: Molecular biology adrenal gland aging CP: Developmental biology skeletal muscle circadian clock hypothalamus heart
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Summary:	Cellular circadian clocks direct a daily transcriptional program that supports homeostasis and resilience. Emerging evidence has demonstrated age-associated changes in circadian functions. To define age-dependent changes at the systems level, we profile the circadian transcriptome in the hypothalamus, lung, heart, kidney, skeletal muscle, and adrenal gland in three age groups. We find age-dependent and tissue-specific clock output changes. Aging reduces the number of rhythmically expressed genes (REGs), indicative of weakened circadian control. REGs are enriched for the hallmarks of aging, adding another dimension to our understanding of aging. Analyzing differential gene expression within a tissue at four different times of day identifies distinct clusters of differentially expressed genes (DEGs). Increased variability of gene expression across the day is a common feature of aged tissues. This analysis extends the landscape for understanding aging and highlights the impact of aging on circadian clock function and temporal changes in gene expression. [Display omitted] •The number of rhythmically expressed genes (REGs) decline across all tissues with age•REGs in young tissues are enriched for the aging hallmarks•Age-specific differentially expressed genes cluster at specific times of the day•Increase in gene expression variability is a common feature of aging tissues Wolff et al. provide an overview of the impact of chronological age on mRNA circadian rhythms in multiple tissues from male mice. Across the organs, there are age-related declines in the number of genes exhibiting circadian expression patterns.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 AUTHOR CONTRIBUTIONS Conceptualization, C.A.W., M.A.G., A.C.L., M.L.G., A.J.B., and K.A.E.; methodology, C.A.W., L.M., Z.H.; investigation, C.A.W., X.Z., M.A.G., C.M.D., A.R.M., M.M.E., E.E., E.A.S., and B.P.D.; writing – original draft, C.A.W., M.A.G., A.C.L., and K.A.E.; writing – review & editing, all authors reviewed and approved the final version of this manuscript; funding acquisition, B.P.D., A.J.B., M.L.G., Z.H., A.C.L., and K.A.E.; resources, A.C.L., M.L.G., A.J.B., Z.H., and K.A.E.; supervision, A.C.L., M.L.G., Z.H., A.J.B., and K.A.E.
ISSN:	2211-1247 2211-1247
DOI:	10.1016/j.celrep.2022.111982