Development and validation of a modified phenoage for biological aging and chronic diseases in a chinese cohort

OBJECTIVE: To address the original PhenoAge's reliance on C-reactive protein (CRP)-a non-routine clinical biomarker-and enhance practical utility in routine healthcare settings, we developed a modified algorithm (PA-CRP) excluding CRP while retaining its core multi-omics integration framework, and further evaluated its associations with chronic diseases and lifestyle factors in a Chinese cohort. METHODS: Both PA-CRP and its derivative PA-CRP_Advance (biological age minus chronological age) were first developed and validated for their validity based on the NHANES dataset. Subsequently, the algorithm was applied to a Chinese university-based cohort (n = 4295), with multivariable logistic and linear regression models (adjusted for key confounders) to assess associations with chronic conditions and lifestyle factors. RESULTS: PA-CRP demonstrated strong validity in reflecting biological aging and predicting mortality. In the Chinese cohort, it was significantly associated with hypertension, hyperlipidemia, hyperglycemia, and cataracts, while PA-CRP_Advance showed targeted links to hyperuricemia and hyperglycemia. Smoking was confirmed as a key driver of accelerated biological aging, and physical activity exhibited a non-linear protective effect; alcohol consumption showed no significant association. CONCLUSION: PA-CRP is a valid, pragmatic tool for assessing biological aging and chronic disease risk in Chinese adults. Its exclusion of CRP enables broad application in routine clinical and public health contexts where CRP is unavailable, supporting its utility as a cross-population applicable biological aging metric.