Moderate-to-severe olfactory dysfunction marks accelerated phenotypic aging in U.S. adults

Olfactory dysfunction (OD) predicts mortality in older adults, but whether it indexes systemic biological aging at clinically meaningful severity thresholds is unresolved. In 3,519 U.S. adults aged ≥40 years in NHANES 2013–2014 with mortality follow-up through 2019, moderate-to-severe OD (≥4 of 8 odors incorrectly identified; weighted prevalence 6.3%) was cross-sectionally associated with +2.48 years of phenotypic aging acceleration (95% CI: +0.79 to +4.16; p = 0.0039; narrowly surviving Bonferroni across 12 primary tests), with 69.1% of the effect jointly mediated through renal, inflammatory, hepatic, and metabolic biomarker domains. During 5.9-year median follow-up (373 deaths), OD ≥4 predicted all-cause mortality (HR = 1.76; 95% CI: 1.32–2.34) and cardiovascular mortality (Fine-Gray sHR = 1.61, 95% CI: 1.20–2.16; p = 0.002). Effects concentrated in adults with chronic cardiometabolic disease. Age-and-sex-standardized 5-year mortality was 13.3% with OD ≥4 versus 6.8% without—a 6.5-percentage-point absolute-risk increase. However, decision-curve analysis showed negative net benefit at clinically actionable thresholds and unfavorable reclassification (continuous NRI = −0.157), positioning OD ≥4 as a biological-aging research signal rather than a clinical risk-stratification adjunct. External replication in non-NHANES cohorts is required before the ≥4 cutoff can be treated as a validated biological threshold.