Association between epigenetic clock acceleration and malnutrition among adults in the United States: A cross‐sectional study

Abstract Background We investigated relationships between nutrition assessment tools (Controlling Nutritional Status [CONUT], Geriatric Nutritional Risk Index [GNRI], and Naples Prognostic Score [NPS]) and epigenetic clocks, evaluating malnutrition's impact on biological aging. Methods Using National Health and Nutrition Examination Survey database (1999–2002), 2532 participants aged ≥50 years were assessed with three nutrition tools and analyzed against 12 epigenetic clocks using multiple linear regression models adjusted for confounding factors. Results Malnutrition prevalence rates were 13.5% (CONUT), 4.2% (GNRI), and 46.8% (NPS). Compared with no‐risk groups, moderate‐to‐severe malnutrition showed significant epigenetic age acceleration, particularly in NPS assessment. GrimAge2Mort demonstrated up to 4.19 years acceleration (in NPS model 3, P < 0.01), DunedinPoAm showed significant increase (in NPS model 3, β = 0.083, P < 0.01), and YangCell significantly decreased (in NPS model 3, β = −0.019, P < 0.01). These associations remained significant after adjusting for confounding factors. A clear dose‐response relationship existed between malnutrition and epigenetic age acceleration. Conclusion This study provides first systematic evidence of significant associations between malnutrition and epigenetic age acceleration, particularly in moderate‐to‐severe malnutrition, leading to substantial biological aging acceleration. GrimAge2Mort, DunedinPoAm, and YangCell emerged as stable indicators for assessing nutrition‐related biological aging. These findings provide new insights into malnutrition's impact on aging and offer important references for clinical nutrition intervention strategies.