BACKGROUND: Biological age (BA) is a more accurate indicator of aging-related functional decline and disease risk than chronological age (CA). Insulin resistance and chronic inflammation are established hallmarks linked to the aging process; however, their synergistic relationship with biological age acceleration is not yet well understood.
METHODS: To evaluate the independent and synergistic associations of estimated glucose disposal rate (eGDR), a marker of insulin sensitivity, and neutrophil-to-albumin ratio (NPAR), a reliable marker of systemic inflammation that also captures its impact on metabolic processes, with biological age acceleration estimated by Klemera-Doubal method biological age (KDM-BA) and PhenoAge. We analyzed cross-sectional data from 35,169 U.S. adults aged ≥20 years in National Health and Nutrition Examination Survey (NHANES) 1999-2010 and 2015-2018. Biological age acceleration was defined as BA exceeding chronological age. Multivariable regression and restricted cubic spline models were used to assess linear and nonlinear associations. We examined the combined association of eGDR and NPAR with aging markers, adjusting for a comprehensive set of demographic, lifestyle, and comorbidity covariates.
RESULTS: In fully adjusted models, eGDR was robustly and inversely associated with KDM-BA acceleration (OR per 1-unit increase: 0.69, 95 % CI: 0.67-0.72). Compared to the lowest tertile, participants in the highest eGDR tertile had a 83 % lower odds of KDM-BA acceleration (OR = 0.17, 95 % CI: 0.14-0.20). No significant association was observed between eGDR and PhenoAge acceleration. Conversely, higher NPAR was positively associated with acceleration of both KDM-BA (OR per unit increase 1.12, 95 % CI: 1.10-1.14) and PhenoAge (OR per unit increase 1.27, 95 % CI: 1.24-1.30). Participants in the highest NPAR tertile exhibited significantly increased odds of accelerated aging compared to the lowest tertile (KDM-BA acceleration OR = 1.90, 95 % CI: 1.53-2.36; PhenoAge acceleration OR = 3.39, 95 % CI: 2.91-3.95). Both biomarkers showed significant nonlinear dose-response relationships with aging outcomes. Notably, combined exposure to low eGDR and high NPAR conferred the greatest risk of accelerated aging, with OR of 5.46 (95 % CI: 4.60-6.48) for KDM-BA and 2.98 (95 % CI: 2.46-3.62) for PhenoAge. Subgroup analyses revealed significant heterogeneity, with associations varying by BMI and chronic kidney disease status.
CONCLUSION: Reduced insulin sensitivity and heightened inflammation-nutrition imbalance are independently and synergistically associated with accelerated biological aging. The interplay between eGDR and NPAR, particularly their joint effect, highlights the pivotal role of the metabolic-inflammatory axis in the aging process. These findings suggest that combined monitoring of eGDR and NPAR could be a valuable strategy for early risk stratification and the development of personalized anti-aging interventions.
