Epigenetic aging and blood based neurodegeneration markers in LASI-DAD.

Jung Ki Kim, Thalida E Arpawong, Bharat Thyagarajan, Jennifer A Smith, Sithara Vivek, Scott Ratliff, Sharmistha Dey, Jinkook Lee, Eileen M Crimmins

Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA. Electronic address: [email protected] School of Gerontology, University of Southern California, Los Angeles, CA, USA. Electronic address: [email protected]. · pubmed

Paper

Abstract

DNA methylation (DNAm)-based epigenetic clocks are emerging biomarkers of biological aging and have been linked to cognitive decline and dementia, but their relationship with blood-based neurodegenerative biomarkers remains understudied in low- and middle-income countries (LMIC). Using the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD), we examined whether epigenetic aging was associated with levels and changes in neurodegenerative biomarkers among adults aged ≥60 years. Seven epigenetic clocks were derived from DNAm data and related to plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light (NfL), phosphorylated tau 181 (pTau181), total tau, Amyloid-β (Aβ)42, Aβ40 and Aβ42/Aβ40 measured at two time points. Baseline accelerated epigenetic aging was associated with higher levels of neurodegenerative biomarkers, including pTau181, GFAP, and NfL, with more consistent associations with increases in GFAP and NfL for morbidity- and mortality-trained clocks. These findings support the utility of epigenetic clocks as scalable tools for identifying risk of neurodegeneration in LMIC settings.

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Research summary

Baseline accelerated epigenetic aging is associated with higher levels of neurodegenerative biomarkers in older adults. The study explores the relationship between epigenetic aging and neurodegeneration, which is pertinent to understanding biological aging processes and their implications for longevity.

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