Cellular biomarkers of aging.

Normal human fibroblast-like cells show a declining proliferative capacity with age. Eventually the cultures become senescent and incapable of replicating. Loss of proliferative capacity is characterized by a declining fraction of cells which synthesize DNA in a defined time period, a gradually increasing cell cycle time, and a declining saturation density. For 36 sublines of WI-38 cells and 17 sublines of IMR-90 cells, we have characterized the fraction of cells synthesizing DNA and the saturation density throughout their life spans. These parameters were both related in a regular and consistent way with the percent life span completed and determined retrospectively by cell counts at each subcultivation until phase-out. Thus, these two determinations serve as independent biomarkers for cell culture aging as they relate to one functional parameter--proliferative capacity. As such, they can be used to assess functional age independently of chronological age.