Genetic Correlates of Biological Aging and the Influence on Prediction of Mortality

Background
Longevity and disease-free survival are influenced by a combination of genetics and lifestyle. 
Biological age (BioAge), a measure of aging based on composite biomarkers, may outperform 
chronological age in predicting health and longevity. This study investigated the relationship 
between genetic risks, lifestyle factors and delta age (Δage), estimated as the difference between 
biological and chronological age. 
Methods
BioAge and Δage were calculated for 52,418 participants from the population-based Lifelines 
cohort. We computed two independent polygenic risk scores for healthspan and DNA 
methylation-based aging clock to characterize genetic risks. The capacity of BioAge to predict 
all-cause mortality when adjusted for chronological age and genetic risks for aging, was 
assessed. 
Results
Obesity, lifestyle, socioeconomic status, sex, and genetic variations in a population contributed to 
the differences in the rates of accelerated aging. After adjusting for chronological age and genetic 
factors, BioAge maintained its sensitivity for predicting mortality. 
Conclusion
2
Findings from this study ascertain that BioAge can be a useful tool for risk stratification in 
research and aging interventions. 
Keywords: lifestyle, environmental influences, polygenic scores, accelerated aging, longevity