A reliable model of biological age is instrumental in the field of geriatrics and gerontology. This model should account for the heterogeneity and plasticity of aging and also accurately predict aging-related adverse outcomes. Epigenetic age models are based on DNA methylation levels at selected genomic sites and can be significant predictors of mortality and healthy/unhealthy aging. However, the biological function of DNA methylation at selected sites is yet to be determined. Frailty is a syndrome resulting from decreased physiological reserves and resilience. The frailty index is a probability-based extension of the concept of frailty. Defined as the proportion of health deficits, the frailty index quantifies the progression of unhealthy aging. The frailty index is currently the best predictor of mortality. It is associated with various biological factors and provides insight into the biological processes of aging. Investigation of the multi-omics factors associated with the frailty index will provide further insight.