Association of aging acceleration with serum neurofilament light chain levels: Implications for the roles of modifiable aging factors

INTRODUCTION: Neurofilament light chain (NfL) is a specific biomarker of neuroaxonal damage and related neurodegenerative diseases. Aging acceleration, which reflects the impact of modifiable factors on the aging process, is increasingly recognized for its relevance. While normal aging is known to contribute substantially to neuroaxonal damage and many neurodegenerative diseases, the effects of aging acceleration warrant further investigation. This study aimed to investigate the association and causality between aging acceleration and serum NfL levels. METHODS: We conducted a cross-sectional study involving 1695 adult participants from NHANES 2013-2014 to evaluate the association, dose-response relationship, and interaction network between aging acceleration and serum NfL levels. And we used Mendelian randomization (MR) to assess the causal effects between serum NfL levels and aging acceleration. RESULTS: Significant positive associations were observed between aging acceleration and serum NfL levels. In linear regression, the regression coefficients were 0.016 (95 % CI: 0.011-0.021) for biological age acceleration and 0.020 (95 % CI: 0.012-0.028) for phenotypic age acceleration. In logistic regression, the odds ratios were 1.052 (95 % CI: 1.029-1.076) and 1.093 (95 % CI: 1.064-1.123), respectively. Restricted cubic spline regression identified significant positive dose-response relationships, and bidirectional MR analyses demonstrated forward causal effects. CONCLUSION: Our study indicates that aging acceleration is significantly associated with serum NfL levels, with higher levels of aging acceleration linked to an increased risk of neuroaxonal damage. These findings provide robust evidence that aging acceleration affects the risk of neuroaxonal damage and highlight the importance of modifiable aging factors.