title: Historical claims and current interpretations of replicative aging.
abstract: Replicative aging is the process by which most normal human cells "count" the number of times they have divided, eventually undergoing a growth arrest termed cellular senescence. This process is dependent on the shortening of telomeres, repeated sequences at the ends of the chromosomes. The loss of telomeric sequences with each cell division eventually induces a growth arrest that has a similar phenotype to that of cells stressed by inadequate culture or other conditions. Experiments over the past several years have identified species in which replicative aging does not occur and many examples in which a failure to proliferate has been misinterpreted as replicative senescence. Insights from these studies now permit a reevaluation of much of the seemingly contradictory data concerning replicative aging. There are good theoretical reasons for believing a limited proliferative capacity contributes to declining tissue homeostasis with increasing age. Although the presence of telomere shortening provides strong circumstantial evidence that replicative aging is occurring in vivo, thus far there is only very limited direct evidence for actual physiological effects of replicative aging.
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039, USA. Woodring.wright@utsouthwestern.edu
authors.forename: Woodring E
authors.initials: WE
authors.lastname: Wright
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Shay
mesh_terms: D002454:Cell Differentiation; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D019976:Cloning, Organism / Q000009:adverse effects; D004261:DNA Replication; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D013045:Species Specificity; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D016615:Telomere / Q000235:genetics*
chemical_list: D019098:Telomerase