Department of Biomedical Sciences, University of Modena and Reggio Emilia, Via G. Campi 287, Modena, Italy.
Mech Ageing Dev. 2010 Oct;131(10):625-35. doi: 10.1016/j.mad.2010.08.008. Epub 2010 Sep 9.
Several studies have analyzed modulation of gene expression during physiological ageing with interesting, but often contradictory results, depending on the model used. In the present report we compare age-related metabolic and synthetic parameters in human dermal fibroblasts (HDF) isolated from young and old subjects (ex vivo ageing model) and cultured from early up to late cumulative population doublings (CPD) (in vitro ageing model) in order to distinguish changes induced in vivo by the aged environment and maintained in vitro, from those associated with cell senescence and progressive CPD. Results demonstrate that fibroblasts from aged donors, already at early CPD, exhibit an impaired redox balance, highlighting the importance of this parameter during ageing, even in the presence of standard environmental conditions, which are considered optimal for cell growth. By contrast, several proteins, as those related to heat shock response, or involved in endoplasmic reticulum and membrane trafficking, appeared differentially expressed only during in vitro ageing, suggesting that, at high CPD, the whole cell machinery becomes permanently altered. Finally, given the importance of the elastic component for a long-lasting connective tissue structural and functional compliance, this study focuses also on elastin and fibulin-5 synthesis and deposition, demonstrating a close relationship between fibulin-5 and ageing.
已有多项研究对生理衰老过程中的基因表达调控进行了分析，结果有趣但往往相互矛盾，这取决于所采用的模型。在本报告中，我们比较了取自年轻和老年供体的人真皮成纤维细胞（HDF）的年龄相关代谢和合成参数（取自体外衰老模型），以及从早期到晚期累积倍增数（CPD）的培养（取自体外衰老模型），以便区分由衰老环境引起并在体外维持的变化，与与细胞衰老和渐进性 CPD 相关的变化。结果表明，即使在标准环境条件下（被认为是细胞生长的最佳条件），来自老年供体的成纤维细胞在早期 CPD 时就已经表现出氧化还原平衡受损，这突出了该参数在衰老过程中的重要性。相比之下，一些蛋白质，如与热休克反应相关的蛋白质或参与内质网和膜运输的蛋白质，仅在体外衰老过程中表现出差异表达，这表明在高 CPD 时，整个细胞机制会永久改变。最后，鉴于弹性成分对持久结缔组织结构和功能顺应性的重要性，本研究还集中在弹性蛋白和纤维蛋白聚糖-5 的合成和沉积上，证明了纤维蛋白聚糖-5 与衰老之间的密切关系。
