Online ISSN: 1945-4589

Aging | DNA Methylation-Based Measures of Biological Aging and Cognitive Decline Over 16-years: Preliminary Longitudinal Findings in Midlife

12-29-2022

“This is the first report to explore changes over time in several of the latest DNAm biological aging measures [...]”

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BUFFALO, NY- December 29, 2022 – A new research paper was published in Aging (listed as "Aging (Albany NY)" by MEDLINE/PubMed and "Aging-US" by Web of Science) Volume 14, Issue 23, entitled, “DNA methylation-based measures of biological aging and cognitive decline over 16-years: preliminary longitudinal findings in midlife.”

DNA methylation-based (DNAm) measures of biological aging associate with increased risk of morbidity and mortality, but their links with cognitive decline are less established. 

In this new study, researchers Rebecca G. Reed, Judith E. Carroll, Anna L. Marsland, and Stephen B. Manuck from University of Pittsburgh and University of California examined changes over a 16-year interval in epigenetic clocks (the traditional and principal components [PC]-based Horvath, Hannum, PhenoAge, GrimAge) and pace of aging measures (Dunedin PoAm, Dunedin PACE) in 48 midlife adults enrolled in the longitudinal arm of the Adult Health and Behavior project (56% Female, baseline AgeM = 44.7 years), selected for discrepant cognitive trajectories. 

“We hypothesized that overall, cognitive Decliners would be biologically older compared to cognitive Maintainers.”

Cognitive Decliners (N = 24) were selected based on declines in a composite score derived from neuropsychological tests and matched with participants who did not show any decline, Maintainers (N = 24). Multilevel models with repeated DNAm measures within person tested the main effects of time, group, and group by time interactions. DNAm measures significantly increased over time generally consistent with elapsed time between study visits. 

There were also group differences: overall, Cognitive Decliners had an older PC-GrimAge and faster pace of aging (Dunedin PoAm, Dunedin PACE) than Cognitive Maintainers. There were no significant group by time interactions, suggesting accelerated epigenetic aging in Decliners remained constant over time. Older PC-GrimAge and faster pace of aging may be particularly sensitive to cognitive decline in midlife.

“In conclusion, these preliminary results suggest PC-GrimAge and DNAm based pace of aging measures (Dunedin PoAm and PACE) associate with 16-year, neuropsychologically-validated cognitive decline in midlife. The results warrant a larger-scale study to better examine longitudinal associations between changes in DNAm measures and changes across multiple cognitive domains. Ultimately, establishing DNAm measures as biomarkers of cognitive function in midlife may offer pre-clinical markers of a molecular aging mechanism that can help identify individuals at increased risk for cognitive impairment and dementia in later life.”

DOI: https://doi.org/10.18632/aging.204376 

Corresponding Author: Rebecca G. Reed - rebecca.reed@pitt.edu 

Keywords: epigenetic age, aging biomarker, pace of aging, geroscience, cognitive aging

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About Aging-US:

Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases.

Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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