title: Relation between replicative senescence of human fibroblasts and life history characteristics.
abstract: Replicative ageing of fibroblasts in vitro has often been used as a model for organismal ageing. The general assumption that the ageing process is mirrored by cellular senescence in vitro is based on lower replicative capacity of human fibroblasts from patients with accelerated ageing syndromes, patients with age related diseases such as diabetes mellitus, and donors of higher chronological age, but these inverse relations have not been reported unequivocally. Therefore, we have performed a formal review on the replicative capacity of fibroblasts from patients suffering from accelerated ageing syndromes, age related diseases and donor age. Some 13 studies including 79 patients with accelerated ageing syndromes showed replicative capacity of fibroblasts to be consistently lower when compared to fibroblasts obtained from age-matched controls. Some 12 studies reported on a total of 160 patients with various age related diseases, but compared to age-matched controls no consistent difference in replicative capacity was reported. Finally, in the period from 1964 to 2006 a total of 23 studies, including some 1115 individuals, reported on the relation between chronological age and replicative capacity of human fibroblasts. Earlier studies preferentially described an inverse relation between replicative capacity and chronological age that was absent in studies including higher numbers of subjects and were published more recently. There was marked heterogeneity between the studies (Egger test: p = 0.018) indicating that publication bias is at play. We conclude that, except for premature ageing syndromes, replicative capacity of fibroblasts in vitro does not mirror key characteristics of human life histories.
authors.affiliation: Leiden University Medical Centre, Department of Gerontology and Geriatrics, 2300 RC Leiden, The Netherlands. a.b.maier@lumc.nl
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Maier
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
mesh_terms: D000375:Aging / Q000502:physiology*; D019588:Aging, Premature / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D002453:Cell Cycle / Q000502:physiology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology*; D004261:DNA Replication / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D015203:Reproducibility of Results