From the Hayflick mosaic to the mosaics of ageing. Role of stress-induced premature senescence in human ageing.
The Hayflick limit-senescence of proliferative cell types-is a fundamental feature of proliferative cells in vitro. Various human proliferative cell types exposed in vitro to many types of subcytotoxic stresses undergo stress-induced premature senescence (SIPS) (also called stress-induced premature senescence-like phenotype, according to the definition of senescence). The known mechanisms of appearance the main features of SIPS are reviewed: senescent-like morphology, growth arrest, senescence-related changes in gene expression, telomere shortening. Long before telomere-shortening induces senescence, other factors such as culture conditions or lack of 'feeder cells' can trigger either SIPS or prolonged reversible G(0) phase of the cell cycle. In vivo, 'proliferative' cell types of aged individuals are likely to compose a mosaic made of cells irreversibly growth arrested or not. The higher level of stress to which these cells have been exposed throughout their life span, the higher proportion of the cells of this mosaic will be in SIPS rather than in telomere-shortening dependent senescence. All cell types undergoing SIPS in vivo, most notably the ones in stressful conditions, are likely to participate in the tissular changes observed along ageing. For instance, human diploid fibroblasts (HDFs) exposed in vivo and in vitro to pro-inflammatory cytokines display biomarkers of senescence and might participate in the degradation of the extracellular matrix observed in ageing.
Department of Biology, Research Unit of Cellular Biology (URBC), University of Namur, Rue de Bruxelles 61, B-5000, Namur, Belgium. olivier.toussaint@fundp.ac.be
Olivier
O
Toussaint
Jose
J
Remacle
Jean-François
JF
Dierick
Thierry
T
Pascal
Christophe
C
Frippiat
Stéphanie
S
Zdanov
Joao Pedro
JP
Magalhaes
Véronique
V
Royer
Florence
F
Chainiaux
D000375:Aging / Q000502:physiology*; D018929:Cell Culture Techniques; D002455:Cell Division / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology*; D006801:Humans; D008017:Life Expectancy; D008954:Models, Biological; D016615:Telomere / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1