Unraveling Stochastic Aging Processes in Mouse Liver: Dissecting Biological from Chronological Age

Abstract Cellular damage accumulation is a central feature of aging, resulting in functional decline and increased vulnerability to pathology and disease. This accumulation occurs over time, but is not exclusively time-dependent. Recent studies showed that, concerning biomedical issues, age may rather be defined as biological age, expressed as the cumulative change of physiological or functional parameters, in contrast to chronological age. We describe a method that goes beyond chronological age as the primary determinant for aging in the investigations of mechanisms underlying aging. We show in mice that the use of biological phenotypes reveals processes, genes, and pathways related to aging that would not have been revealed when using chronological age as the main determinant of aging. Using determinants of biological aging will improve our knowledge regarding the mechanisms underlying aging and may lead to the discovery of new biomarkers of frailty valuable for predicting health risks.