Abstract: Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that composite clinical measures of “phenotypic age”, may facilitate the development of a more powerful epigenetic biomarker of aging. Here we show that our newly developed epigenetic biomarker of aging “DNAm PhenoAge” strongly outperforms previous measure in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, physical functioning, and, age-related dementia. It is also associated with Down syndrome, HIV infection, socioeconomic status, and various life style factors such as diet, exercise, and smoking. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and in moving forward, will facilitate the development of anti-aging interventions.