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. 2025 Mar;2(1):1-8.
doi: 10.4103/agingadv.agingadv-d-24-00021. Epub 2025 Feb 6.

Biological aging and its association with serum neurofilament light chain levels in middle-aged African Americans: a prospective observational study

Man-Kit Lei  1 , Mei Ling Ong  2 , Ronald L Simons  1 , Steven R H Beach  3
Affiliations

Biological aging and its association with serum neurofilament light chain levels in middle-aged African Americans: a prospective observational study

Man-Kit Lei et al. Aging Adv. 2025 Mar.

Abstract

This study examines the association between DNA methylation-based epigenetic aging indices and neurofilament light chain levels in middle-aged African Americans to advance the understanding of neurodegeneration and cognitive decline. Epigenetic aging was assessed in samples from 2008 and 2019 by applying HorvathAgeAccel, HannumAgeAccel, PhenoAgeAccel, GrimAgeAccel, and DunedinPACE. Controlling for financial strain, exercise, age, gender, cell-type composition, and APOE-ε4, second- and third-generation DNA methylation-based aging-PhenoAgeAccel, GrimAgeAccel, and DunedinPACE-were significantly associated with serum neurofilament light chain levels. In contrast, first-generation DNA methylation-based clocks, including HorvathAgeAccel and HannumAgeAccel, were not significantly related to neurofilament light chain. These findings suggest that newer DNA methylation-based aging indices are more strongly associated with neurodegenerative biomarkers. Integrating advanced DNA methylation-based clocks with neurofilament light chain levels may improve early detection of cognitive decline and dementia, supporting personalized medicine by identifying biological aging profiles linked to neurodegenerative risks.

Keywords: DNA methylation; accelerated epigenetic aging; aging; neurodegeneration; neurofilament light chain.

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Conflict of interest statement

Conflicts of interest: None of the authors has any conflict of interest regarding this article or the research reported therein.

Figures

Figure 1 |
Figure 1 |. A schematic overview of the study.
NfL: Neurofilament light chain.
Figure 2 |
Figure 2 |
Density plot of neurofilament light chain (NfL) levels from adults participating in the Family and Community Health Study (FACHS), 2019.
Figure 3 |
Figure 3 |
Heatmap showing the correlation coefficients among DNA methylation (DNAm)-based aging indices, cortical clock, and logged neurofilament light chain (NfL) levels from adults participating in the Family and Community Health Study (FACHS), 2019.
Figure 4 |
Figure 4 |
Depicts the change in logged neurofilament light chain (NfL) levels in adults participating in the Family and Community Health Study (FACHS) from 2008 to 2019, in association with (A) PhenoAgeAccel, (B) GrimAgeAccel, and (C) DunedinPACE.
See this image and copyright information in PMC

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