Lipid–adiposity dissociation in nonagenarians

Abstract Anthropometric measures such as waist-to-height ratio (WHtR) and body mass index (BMI) are widely used to assess metabolic health in the general population. However, their relevance in individuals with exceptional longevity remains unclear. In this study, we investigated the relationship between plasma lipid profiles and anthropometric measures in 182 nonagenarians (aged 90–100) and 306 adults (aged 25–60). Using direct-infusion mass spectrometry, we quantified 195 lipid species across 14 lipid classes and examined their associations with WHtR and BMI in sex-stratified analyses. In adults, we observed statistically significant correlations between multiple lipid classes and anthropometric measures, consistent with established metabolic patterns. Remarkably, these associations were substantially weakened in nonagenarians, with TGs and DAGs showing the greatest age-group divergence. Predictive modeling showed that an adult-trained lipid model did not accurately estimate WHtR or BMI in nonagenarians, systematically underestimating adiposity at higher values. Accordingly, long-living individuals exhibiting metabolically healthy lipidome profiles would have been classified as high-risk by conventional adult WHtR and BMI thresholds. Taken together, the observed weakening of the relationship between adiposity metrics and lipid metabolism in extreme old age may inform further discussion of old-age adiposity assessment and longevity-promoting strategies.