Effects of aging on circadian patterns of gene expression in the human prefrontal cortex
Open accessAbstract
With aging, significant changes in circadian rhythms occur, including a shift in phase toward a "morning" chronotype and a loss of rhythmicity in circulating hormones. However, the effects of aging on molecular rhythms in the human brain have remained elusive. Here, we used a previously described time-of-death analysis to identify transcripts throughout the genome that have a significant circadian rhythm in expression in the human prefrontal cortex [Brodmann's area 11 (BA11) and BA47]. Expression levels were determined by microarray analysis in 146 individuals. Rhythmicity in expression was found in ∼ 10% of detected transcripts (P < 0.05). Using a metaanalysis across the two brain areas, we identified a core set of 235 genes (q < 0.05) with significant circadian rhythms of expression. These 235 genes showed 92% concordance in the phase of expression between the two areas. In addition to the canonical core circadian genes, a number of other genes were found to exhibit rhythmic expression in the brain. Notably, we identified more than 1,000 genes (1,186 in BA11; 1,591 in BA47) that exhibited age-dependent rhythmicity or alterations in rhythmicity patterns with aging. Interestingly, a set of transcripts gained rhythmicity in older individuals, which may represent a compensatory mechanism due to a loss of canonical clock function. Thus, we confirm that rhythmic gene expression can be reliably measured in human brain and identified for the first time (to our knowledge) significant changes in molecular rhythms with aging that may contribute to altered cognition, sleep, and mood in later life.
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Disruptions in circadian biology arising from aging are believed to underlie the change in chronotype in older adults.
“In relation to older adults, disruptions in circadian biology arising from the aging process are believed to underlie the change in chronotype (54)”
From Chronotype: Implications for Epidemiologic Studies on Chrono-Nutrition and Cardiometabolic Health (2019) · cites this paper as [54]
In older adults, rhythms often return to being substantially earlier, and this shift may be accompanied by a weakening of circadian rhythms.
“In older adults, rhythms often return to being substantially earlier, and this shift may be accompanied by a weakening of circadian rhythms11,12.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [11]
Gene expression rhythms in the human mPFC decline with age, and a separate set of genes becomes newly rhythmic in older people aged 65 years and older.
“gene expression rhythms in the human mPFC also decline with age; however, surprisingly, a separate set of genes becomes newly rhythmic in older people (aged 65 years and older)11”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [11]
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- Authors
- Chen, C.-Y., Logan, R. W., Ma, T., Lewis, D. A., Tseng, G. C., Sibille, E., & McClung, C. A.
- Affiliations
- University of Pittsburgh (US)
- Centre for Addiction and Mental Health (CA)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-12-22
- Volume
- 113
- Issue
- 1
- Pages
- 206-211
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4711850
- OpenAlex
- W2217406169
- Cited by
- 277
- References
- 60
- Citations by year
- 2026: 27 · 2025: 33 · 2024: 26 · 2023: 30 · 2022: 27 · 2021: 22 · 2020: 36 · 2019: 19 · 2018: 18 · 2017: 27 · 2016: 11
- FWCI
- 10.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Mental Health (R01MH077159, R01MH093723, MH103204)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- circadian rhythm, gene expression, brain aging, prefrontal cortex, clock genes, compensatory gene expression, cognitive aging
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Circadian Rhythm, Gene Expression Regulation, Humans, Male, Middle Aged, Sleep, Transcription, Genetic, Genome, Human, Prefrontal Cortex, Oligonucleotide Array Sequence Analysis, Young Adult
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