Biomarkers of Human Aging

Several promising interventions have been demonstrated to promote longevity and healthspan in animal models. However, parallel human studies remain unfeasible based on the 40+ years of investigation likely required to complete such studies. Therefore, the National Institute on Aging has prioritized efforts to develop reliable biomarkers of human biological age. Multiple lines of evidence from our group and others indicate that the bioenergetic profiles of blood cells are related to multiple age-related diseases and disorders. Based on these findings, we have embarked on a new collaboration to test the hypothesis that peripheral blood cells exhibit epigenetic, transcriptomic, as well as bioenergetic changes related to fundamental mechanisms of human aging.

Circulating factors mediating systematic age-related bioenergetic decline

Blood-borne factors play a central role in aging. Using parabiosis, researchers have demonstrated that connecting the circulatory systems of young and old animals has systemic “rejuvenating” effects for the older animal. Conversely, our preliminary data demonstrate that factors present in the blood of older animals mediate age-related bioenergetic decline. By utilizing a heterochronic parabiosis mouse model, we observe that the bioenergetic capacity of skeletal muscle in young parabionts is severely diminished and quantitatively similar to parallel measures performed in the older parabionts as well as isochronic (old/old) controls. Various classes of circulating factors, including peptides, lipid metabolites, RNAs, and cytokines are being investigated for their roles in aging and various age-related diseases/disorders. However, it is unlikely that any single factor can be wholly responsible for the systemic effects of blood. To address this complexity, we are developing a novel systematic approach for studying human serum, and its components, in-vitro to identify circulating factor/s responsible for mediating changes in systemic bioenergetic capacity.