Eleven Telomere, Epigenetic Clock, and Biomarker-Composite Quantifications of Biological Aging: Do They Measure the Same Thing?

Abstract

The geroscience hypothesis posits that therapies to slow biological processes of aging can prevent disease and extend healthy years of life. To test such "gero-protective" therapies in humans, outcome measures are needed that can assess extension of disease-free lifespan. 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 seven methods to quantify biological aging using repeated-measures physiological and genomic data in 964 middle-aged humans in the Dunedin Study. We studied telomere-length and erosion, three epigenetic-clocks and their ticking rates, and three biomarker-composites, 11 measures in total. Contrary to expectation, we found low agreement between different measures of biological aging. We next compared associations between biological aging measures and outcomes gero-protective therapies seek to modify: physical functioning, cognitive decline, and subjective signs of aging, including aged facial appearance. The 71-CpG epigenetic clock and biomarker composites were consistently related to these aging-related outcomes. However, effect-sizes were modest. Results suggests 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.