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

Christopher A Wolff; Miguel A Gutierrez-Monreal; Lingsong Meng; Xiping Zhang; Lauren G Douma; Hannah M Costello; Collin M Douglas; Elnaz Ebrahimi; Ann Pham; Aline C Oliveira; Chunhua Fu; Amy Nguyen; Bryan R Alava; Stuart J Hesketh; Andrew R Morris; Mehari M Endale; G Ryan Crislip; Kit-Yan Cheng; Elizabeth A Schroder; Brian P Delisle; Andrew J Bryant; Michelle L Gumz; Zhiguang Huo; Andrew C Liu; Karyn A Esser

doi:10.1016/j.celrep.2022.111982

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

Cell Rep. 2023 Jan 31;42(1):111982. doi: 10.1016/j.celrep.2022.111982. Epub 2023 Jan 9.

Authors

Christopher A Wolff¹, Miguel A Gutierrez-Monreal², Lingsong Meng³, Xiping Zhang¹, Lauren G Douma⁴, Hannah M Costello⁴, Collin M Douglas¹, Elnaz Ebrahimi⁵, Ann Pham⁵, Aline C Oliveira⁵, Chunhua Fu⁵, Amy Nguyen⁵, Bryan R Alava⁶, Stuart J Hesketh¹, Andrew R Morris⁶, Mehari M Endale⁶, G Ryan Crislip⁷, Kit-Yan Cheng⁷, Elizabeth A Schroder⁸, Brian P Delisle⁹, Andrew J Bryant¹⁰, Michelle L Gumz¹¹, Zhiguang Huo¹², Andrew C Liu¹³, Karyn A Esser¹⁴

Affiliations

¹ Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Myology Institute, University of Florida, Gainesville, FL 32610, USA.
² Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Myology Institute, University of Florida, Gainesville, FL 32610, USA; Claude D. Pepper Older Americans Independence Center, University of Florida, Gainesville, FL 32610, USA.
³ Department of Biostatistics, University of Florida, Gainesville, FL 32610, USA.
⁴ Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA.
⁵ Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
⁶ Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
⁷ Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
⁸ Internal Medicine, Pulmonary, University of Kentucky, Lexington, KY 40506, USA; Department of Physiology, University of Kentucky, Lexington, KY 40506, USA.
⁹ Department of Physiology, University of Kentucky, Lexington, KY 40506, USA.
¹⁰ Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA.
¹¹ Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA; Center for Integrative Cardiovascular and Metabolic Disease, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
¹² Department of Biostatistics, University of Florida, Gainesville, FL 32610, USA. Electronic address: zhuo@ufl.edu.
¹³ Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA. Electronic address: andrew.liu@ufl.edu.
¹⁴ Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Myology Institute, University of Florida, Gainesville, FL 32610, USA; Claude D. Pepper Older Americans Independence Center, University of Florida, Gainesville, FL 32610, USA. Electronic address: kaesser@ufl.edu.

Abstract

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.

Keywords: CP: Developmental biology; CP: Molecular biology; RNA-seq; adrenal gland; aging; circadian clock; heart; hypothalamus; kidney; lung; skeletal muscle.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aging / genetics
Aging / metabolism
Animals
Circadian Clocks* / genetics
Circadian Rhythm / genetics
Hypothalamus
Male
Mice
Transcriptome* / genetics

Abstract

Publication types

MeSH terms

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