Microscopic Imaging of Epigenetic Age

Predictive biomarkers of functional or biological age are key for evaluating interventions aimed at increasing healthspan and / or lifespan in humans. Currently, cardiovascular performance, blood analytes, frailty indices, and DNA methylation clocks are used to provide such estimates; each technique has its own challenges and limitations. We have developed a novel approach, microscopic imaging of biological age (miBioAge), which computes multiparametric signatures based on the patterns of epigenetic landscape in single nuclei. We demonstrated that such miBioAge readouts can robustly distinguish young and old cells from multiple tissues, reveal aging progression in peripheral blood (e.g. CD3+ T cells), and reflect changes of epigenetic signatures consistent with expected slowdown or acceleration of biological age in chronologically identical mice treated with caloric restriction or chemotherapy. Because miBioAge readouts are computed from individual samples without applying linear regression, we posit that this novel biomarker may provide personalized assessment of functional aging.