Liu · PLoS medicine 2018 · prospective cohort study · n=11,617

A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study.

Cited 740 times in the scientific literature.

Level 3 - non-randomized controlled study

Prospective cohort study analyzing mortality outcomes over follow-up

PubMed 30596641 · doi:10.1371/journal.pmed.1002718 · record verified 2026-08-30

What was done

The authors evaluated Phenotypic Age and Phenotypic Age Acceleration (PhenoAgeAccel)—calculated from chronological age and 9 routine clinical chemistry biomarkers—in an independent cohort of NHANES IV participants (1999–2010). The analytic sample comprised 11,432 adults aged 20–84 years and 185 oldest-old adults aged 85 years and older. Proportional hazard models and receiver operating characteristic curves were used to analyze 1,012 deaths ascertained over up to 12.6 years of follow-up via the National Death Index across diverse demographic, socioeconomic, behavioral, and health strata.

What was found

Participants with more diseases exhibited older Phenotypic Age; among young adults, those with 1 disease were 0.2 years older phenotypically, and those with 2 or 3 diseases were approximately 0.6 years older than disease-free individuals. After adjusting for chronological age and sex, Phenotypic Age significantly predicted all-cause mortality and cause-specific mortality, with the exception of cerebrovascular disease mortality. Associations with all-cause mortality remained robust across subgroups stratified by age, race/ethnicity, education, disease count, and health behaviors, and persisted among disease-free participants with normal BMI as well as the oldest-old.

Why it matters

This study shows that a biological age measure constructed from standard, accessible laboratory tests reliably stratifies mortality and morbidity risk beyond chronological age across diverse population groups.

Limits

The study lacked longitudinal repeat measures of Phenotypic Age and longitudinal data on incident non-fatal disease. Biomarker performance was not significantly predictive for cerebrovascular mortality, and the cohort was limited to US adults.

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