Toussaint Olivier, Remacle Jose, Dierick Jean-François, Pascal Thierry, Frippiat Christophe, Zdanov Stéphanie, Magalhaes Joao Pedro, Royer Véronique, Chainiaux Florence
Department of Biology, Research Unit of Cellular Biology (URBC), University of Namur, Rue de Bruxelles 61, B-5000, Namur, Belgium.
Int J Biochem Cell Biol. 2002 Nov;34(11):1415-29. doi: 10.1016/s1357-2725(02)00034-1.
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.
海弗利克极限——增殖细胞类型的衰老——是体外增殖细胞的一个基本特征。多种人类增殖细胞类型在体外暴露于多种亚细胞毒性应激下会经历应激诱导的早衰（SIPS）（根据衰老的定义，也称为应激诱导的早衰样表型）。本文综述了SIPS主要特征出现的已知机制：衰老样形态、生长停滞、基因表达的衰老相关变化、端粒缩短。早在端粒缩短诱导衰老之前，其他因素如培养条件或缺乏“饲养细胞”就可以触发SIPS或细胞周期的延长可逆G(0)期。在体内，老年个体的“增殖”细胞类型可能构成一个由不可逆生长停滞或未停滞的细胞组成的镶嵌体。这些细胞在其整个生命周期中所暴露的应激水平越高，这个镶嵌体中处于SIPS而非端粒缩短依赖性衰老的细胞比例就越高。所有在体内经历SIPS的细胞类型，最显著的是那些处于应激条件下的细胞类型，都可能参与衰老过程中观察到的组织变化。例如，在体内和体外暴露于促炎细胞因子的人二倍体成纤维细胞（HDFs）表现出衰老的生物标志物，并可能参与衰老过程中观察到的细胞外基质降解。
