Feature Selection Algorithms Enhance the Accuracy of Frailty Indexes as Measures of Biological Age

Biological age captures some of the variance in life expectancy for which chronological age is not accountable, and it quantifies the heterogeneity in the presentation of the aging phenotype in various individuals. Among the many quantitative measures of biological age, the mathematically uncomplicated frailty/deficit index is simply the proportion of the total health deficits in various health items surveyed in different individuals. We used 3 different statistical methods that are popular in machine learning to select 17-28 health items that together are highly predictive of survival/mortality, from independent study cohorts. From the selected sets, we calculated frailty indexes and Klemera-Doubal's biological age estimates, and then compared their mortality prediction performance using Cox proportional hazards regression models. Our results indicate that the frailty index outperforms age and Klemera-Doubal's biological age estimates, especially among the oldest old who are most prone to biological aging-caused mortality. We also showed that a DNA methylation index, which was generated by applying the frailty/deficit index calculation method to 38 CpG sites that were selected using the same machine learning algorithms, can predict mortality even better than the best performing frailty index constructed from health, function, and blood chemistry.