S. Michal Jazwinski and Sangkyu Kim
Biological age is a concept that takes into account the heterogeneity of the aging process in different individuals that results in differences in survival and variations in relative health. Any measure of biological age must be better than chronological age at predicting mortality. Several quantitative measures of biological age have been developed. Among them are frailty indices, one of which called FI34 is discussed here in greater detail. FI34 increases exponentially with age reflecting decline in health and function ability. It readily depicts different patterns and trajectories of aging, and it is moderately heritable. Thus, it has been used to identify a genomic region on chromosome 12 associated with healthy aging. FI34 has also been useful in describing the metabolic characteristics of this phenotype, revealing both sex and genetic differences. These differences give rise to specific, testable models regarding healthy aging, which involve cell and tissue damage and mitochondrial metabolism. FI34 has been directly compared to various metrics based on DNA methylation as a predictor of mortality, demonstrating that it outperforms them uniformly. This and other frailty indices take a top-down, systems based view of aging that is cognizant of the integrated function of the complex aging system.