Senescence: the good the bad and the dysfunctional.
Nearly 50 years have elapsed since Hayflick challenged the dogma that individual human cells were immortal by demonstrating that after a predictable number of cellular divisions, normal human fibroblasts eventually entered a state of permanent growth arrest [Hayflick L: The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965, 37:614-636.; Hayflick L, Moorhead PS: The serial cultivation of human diploid cell strains. Exp Cell Res 1961, 25:585-621]. This growth arrest, referred to as senescence, was hypothesized to function as a tumor suppressive mechanism, capable of limiting the replicative capacity of an incipient tumor cell. While originally met with skepticism, the existence of senescence and its importance as a tumor suppressive mechanism is now accepted. Here, we highlight this work and introduce studies that indicate that while senescent cells themselves cannot produce a neoplasia, they possess the ability to promote the growth of nearby preneoplastic cells and in this way may contribute to age-related increases in tumor incidences. This added level of complexity suggests that senescence functions as a biological 'double edged sword.'
Pazolli
Ermira
E
Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Stewart
Sheila A
SA
D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D016922:Cellular Senescence; D006801:Humans; D009369:Neoplasms / Q000209:etiology*; D011230:Precancerous Conditions / Q000473:pathology