Weaker Circadian Rhythms Linked to Accelerated Biological Aging, Study Finds

A study showed that disrupted, weaker circadian rest-activity rhythms were associated with accelerated biological aging, independent of chronic age, sex, and race.1

This research will be presented at SLEEP 2025, the 39th annual meeting of the Associated Professional Sleep Societies, on Tuesday, June 10 in Seattle. The abstract was recently published in an online supplement of the journal Sleep on May 19, 2025.

Circadian alterations are present alongside several poor aging-related outcomes, including neurodegenerative diseases, cardiovascular diseases, and metabolic disorders.2,3,4 However, research had not yet shown that circadian alterations are linked to biological aging.

Investigators, led by Chunyu Liu, MD, PhD student, from the department of mental health at Johns Hopkins Bloomberg School of Public Health, wanted to explore the association between actigraphic circadian rest/activity rhythms with epigenetic age acceleration in older adults.1 They defined epigenetic age acceleration as the difference between epigenetic and chronological age. The sample included 191 participants from the Baltimore Epidemiologic Catchment Area Study Follow-up, with 66% female, 59% White, and a mean age of 68.6±7.7 years.

Participants completed an average of 7.1±1.2 nights of wrist actigraphy and had valid DNA methylation and covariate data. The team used the following actigraphic circadian rest/activity rhythm metrics in their analysis: amplitude, mesor, acrophase, relative amplitude, interdaily stability, interdaily variability, lowest 5-hour activity level or start time, and highest 10-hour activity level or start time. They used DNA methylation data from the Illumina EPIC array to calculate 4 epigenetic clocks, which were GrimAge, PhenoAge, Horvath Clock, and Hannum Clock.

Analyses adjusted for chronical age, sex, and race found that lower amplitude, relative amplitude, interdaily stability, and highest 10-hour activity level, and greater intradaily variability were significantly associated with accelerated aging. The study showed significant associations between accelerated GrimAge and amplitude (0.22 to 1.38), relative amplitude (0.15 to 1.24), interdaily stability (0.03 to 1.20), highest 10-hour activity level (0.15 to 1.3), intradaily variability (-1.45 to -0.35) (P <.05). Accelerated PhenoAge had significant associations with amplitude (0.02 to 2.13) and intradaily stability (0.05 to 2.16) (P <.05).

The Horvath and Hannum clocks showed associations between weaker circadian rest-activity rhythms and advanced biological aging, but findings were not significant.

The study also found that individuals with the lowest 5-hour start time after 1:30 am, compared with those between 12:00 am to 1:30 am, were 1.17 (0.06 to 2.27) years older based on GrimAge.

“Our findings suggest that reduced strength, stability, regularity, and later activity timing of circadian rhythms, are associated with accelerated epigenetic age, notably GrimAge and PhenoAge,” investigators wrote. “These results highlight the role of circadian regulation in aging and underscore the importance of maintaining strong, stable, and well-timed rhythms to mitigate age-related biological deterioration.”

References

1. Chunyu Liu, David Sosnowski, Casandra Nyhuis, Jill Rabinowitz, William Eaton, Nanping Weng, Adam Spira, Brion Maher, 0012 Circadian Rest-Activity Rhythms and Epigenetic Age Acceleration in Older Adults, Sleep, Volume 48, Issue Supplement_1, May 2025, Pages A5–A6, https://doi.org/10.1093/sleep/zsaf090.0012

2. Leng Y, Musiek ES, Hu K, Cappuccio FP, Yaffe K. Association between circadian rhythms and neurodegenerative diseases. Lancet Neurol. 2019 Mar;18(3):307-318. doi: 10.1016/S1474-4422(18)30461-7. Epub 2019 Feb 12. PMID: 30784558; PMCID: PMC6426656.

3. Lecacheur, M., Ammerlaan, D.J.M. & Dierickx, P. Circadian rhythms in cardiovascular (dys)function: approaches for future therapeutics. npj Cardiovasc Health 1, 21 (2024). https://doi.org/10.1038/s44325-024-00024-8

4. Schrader LA, Ronnekleiv-Kelly SM, Hogenesch JB, Bradfield CA, Malecki KM. Circadian disruption, clock genes, and metabolic health. J Clin Invest. 2024;134(14):e170998. Published 2024 Jul 15. doi:10.1172/JCI170998