A BIOMARKER THAT IDENTIFIES SENESCENT HUMAN-CELLS IN CULTURE AND IN AGING SKIN IN-VIVO

Normal somatic cells invariably enter a state of irreversibly arrested growth and altered function after a finite number of divisions. This process, termed replicative senescence, is thought to be a tumor-suppr essive mechanism and an underlying cause of aging. There is ample evid ence that escape from senescence, or immortality, is important for mal ignant transformation. By contrast, the role of replicative senescence in organismic aging is controversial. Studies on cells cultured from donors of different ages, genetic backgrounds, or species suggest that senescence occurs in vivo and that organismic lifespan and cell repli cative lifespan are under common genetic control. However, senescent c ells cannot be distinguished from quiescent or terminally differentiat ed cells in tissues. Thus, evidence that senescent cells exist and acc umulate with age in vivo is lacking. We show that several human cells express a beta-galactosidase, histochemically detectable at pH 6, upon senescence in culture. This marker was expressed by senescent, but no t presenescent, fibroblasts and keratinocytes but was absent from quie scent fibroblasts and terminally differentiated keratinocytes. It was also absent from immortal cells but was induced by genetic manipulatio ns that reversed immortality. In skin samples from human donors of dif ferent age, there was an age-dependent increase in this marker in derm al fibroblasts and epidermal keratinocytes. This marker provides in si tu evidence that senescent cells may exist and accumulate with age in vivo.