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Age-associated changes in human circadian rhythms

Sun, Michelle (2024) Age-associated changes in human circadian rhythms. Master's Thesis, University of Pittsburgh. (Unpublished)

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Cellular circadian clocks support homeostasis by synchronizing essential biological processes to the external day-night cycle. Emerging evidence has demonstrated that the functionality of these clocks changes with age. We leverage data from the Genotype-Tissue Expression project (GTEx) to examine age-dependent changes in rhythmic gene expression programs across 4 human tissues: lung, heart, skeletal muscle, and adrenal gland. Our analysis reveals a shift in the age-related timing of gene expression peaks, transitioning from tissue-specific clustering to a broad categorization at dawn and dusk. We observe a decline in the rhythmicity of genes associated with cell growth and differentiation, paralleled by an increase in the rhythmic expression of genes linked to mitochondrial respiration. We find that the inferred circadian clock outputs are highly dependent on the methodological approach—ordering donors by time-of-death or utilizing circadian phase estimation algorithms leads to different interpretations of the data. Our findings offer insights into the aging transcriptional landscape in humans and highlight the influence of methodology in human circadian rhythm research, providing direction for future studies.

Public Health Significance: Understanding how circadian function changes with age can contribute to strategies aimed at promoting healthy aging, potentially extending the health span and improving quality of life for older adults.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Sun, Michellemps103@pitt.edumps103
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorWang, Jiebiaojbwang@pitt.edujbwang
Committee ChairTseng, George C.ctseng@pitt.eductseng
Committee ChairZhu, Bokaibzhu@pitt.edubzhu
Date: 14 May 2024
Date Type: Publication
Defense Date: 10 April 2024
Approval Date: 14 May 2024
Submission Date: 26 April 2024
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 50
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Biostatistics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: circadian, aging, GTEx, phase estimation
Date Deposited: 14 May 2024 18:41
Last Modified: 14 May 2024 18:41


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