The geroscience hypothesis posits that therapies to slow biological processes of aging can prevent disease and extend healthy years of life. To test such "geroprotective" therapies in humans, outcome measures are needed that can assess extension of disease-free life span. This need has spurred development of different methods to quantify biological aging. But different methods have not been systematically compared in the same humans. We implemented 7 methods to quantify biological aging using repeated-measures physiological and genomic data in 964 middle-aged humans in the Dunedin Study (New Zealand; persons born 1972-1973). We studied 11 measures in total: telomere-length and erosion, 3 epigenetic-clocks and their ticking rates, and 3 biomarker-composites. Contrary to expectation, we found low agreement between different measures of biological aging. We next compared associations between biological aging measures and outcomes that geroprotective therapies seek to modify: physical functioning, cognitive decline, and subjective signs of aging, including aged facial appearance. The 71-cytosine-phosphate-guanine epigenetic clock and biomarker composites were consistently related to these aging-related outcomes. However, effect sizes were modest. Results suggested that various proposed approaches to quantifying biological aging may not measure the same aspects of the aging process. Further systematic evaluation and refinement of measures of biological aging is needed to furnish outcomes for geroprotector trials.
Bibliographical noteFunding Information:
This research received support from the National Institute of Aging (grants R01AG032282, R01AG048895, 1R01AG049789, and R21AG054846), UK Medical Research Council (grant MR/P005918/1), and UK Economic and Social Research Council (grant ES/M010309/ 1). Additional support was provided by the National Institute of Aging (grants P30AG028716 and P30AG034424) and by the Jacobs Foundation. D.W.B. is supported by an Early-Career Research Fellowship from the Jacobs Foundation. A.A.C. is a member of the FRQS-funded Centre de recherche sur le vieillissement and Centre de recherche du CHUS, and holds a Canadian Institute for Health Research New Investigator Salary Award. Conflict of interest: none declared.
- biological aging
- epigenetic clock