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

Lei, Man-Kit1,*; Ong, Mei Ling2; Simons, Ronald L.1; Beach, Steven R.H.

1Department of Sociology, University of Georgia, Athens, GA, USA

2Center for Family Research, University of Georgia, Athens, GA, USA

3Department of Psychology, University of Georgia, Athens, GA, USA

*Correspondence to: Man-Kit Lei, PhD, karlo@uga.edu.

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.

中年美国非裔人群生物衰老及其与血清神经丝蛋白轻链水平的关系：观察性研究

摘要

研究已证实，神经丝蛋白轻链是神经退行性过程的重要指标。此研究探讨了中年美国非裔人群基于 DNA 甲基化 (DNAm) 的衰老指数与神经丝蛋白轻链水平之间的关系，以加深对神经退行性变和认知能力下降的了解。研究显示，第二代和第三代基于DNA 甲基化的指数--PhenoAgeAccel、GrimAgeAccel和DunedinPACE--与中年美国非裔人群血清神经丝蛋白轻链水平之间存在显著关联。然而，第一代DNA 甲基化时钟，如HorvathAgeAccel 和 HannumAgeAccel，与神经丝蛋白轻链没有明显的相关性。这些发现表明，较新的基于DNA 甲基化的衰老指数与神经退行性病变生物标志物的关联性更强。将先进的DNA 甲基化时钟与神经丝蛋白轻链水平结合起来，可以改善中年美国非裔人群认知能力下降和痴呆症的早期检测，通过识别与神经退行性疾病风险相关的生物衰老特征来支持个性化医疗。此研究成果为加强认知功能衰退和神经退行性疾病的预测和管理提供了一条前景广阔的途径。