The blood has something to say: A hematology-based clock to measure aging in mice

Abstract Background : Chronological age alone does not sufficiently explain aging heterogeneity. Biological clocks and molecular biomarkers proposed to predict biological age can be difficult to implement in a clinical setting. Aim: In the framework of translational science, use of routinely collected hematological markers to develop a biological clock to predict biological age and estimate aging acceleration in mice. Methods : Data from 2,562 mice of both sexes and three strains were drawn from the Study of Longitudinal Aging in Mice and from The Jackson Laboratory’s longitudinal study of aging. Fourteen hematological variables and two metabolic indices were collected longitudinally (11,998 observations). Biological age was predicted using a deep neural network. Aging acceleration (positive or negative) was calculated as residuals from a nonlinear regression of predicted age on chronological age and tested for association with all-cause mortality. Results : Biological age was significantly correlated with chronological age (Mean Absolute Error [MAE] = 11.95 weeks, Root Mean Squared Error [RMSE] = 15.41 weeks, r = 0.87) and positive aging acceleration was associated with shorter lifespan. Conclusion : An aging clock based on routinely collected blood measures has the potential to provide a practical clinical tool to better understand individual variability in the aging process.