Remnant cholesterol, serum uric acid, and biological aging: insights from two nationally representative cohorts

Remnant cholesterol (RC) has been linked to cardiometabolic disorders, but its relationship with biological aging across different clinical aging metrics remains unclear. We examined the association of RC with biological aging in two nationally representative cohorts and conducted exploratory mediation analyses of serum uric acid (SUA).

We analyzed data from the U.S. National Health and Nutrition Examination Survey (NHANES 2001-2010; n = 4169) and the China Health and Retirement Longitudinal Study (CHARLS; n = 4672). Biological aging was primarily assessed using the Klemera-Doubal method (KDM), including KDM-based biological aging (KDM-BA) and KDM-based biological age acceleration (KDMAgeAccel). LightAge-based outcomes were additionally evaluated as sensitivity analyses. Multivariable logistic and linear regression models, restricted cubic spline analyses, and two-piecewise regressions were used. In CHARLS, linear mixed-effects models assessed longitudinal changes in biological age.

Higher RC was consistently associated with more advanced biological aging in both cohorts. In fully adjusted models, each 1-SD increase in RC was associated with higher odds of KDM-BA in NHANES (OR 1.40, 95% CI 1.26-1.55) and CHARLS (OR 1.19, 95% CI 1.08-1.31). Positive associations were also observed for LightAge-BA and for continuous outcomes. In NHANES, the associations were nonlinear, whereas in CHARLS they were generally positive across the RC range, with stronger nonlinearity for LightAge-based outcomes. Higher baseline RC quartiles were associated with steeper increases in biological age over follow-up in CHARLS. Exploratory mediation analyses suggested that SUA may account for part of the observed association.

Higher RC levels were consistently associated with more advanced biological aging across two populations and two clinical aging metrics. These findings support RC as a clinically accessible marker associated with adverse biological aging profiles.