Tacutu Robi, Budovsky Arie, Yanai Hagai, Fraifeld Vadim E
The Shraga Segal Department of Microbiology and Immunology, Center for Multidisciplinary Research on Aging, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Aging (Albany NY). 2011 Dec;3(12):1178-91. doi: 10.18632/aging.100413.
The role of cellular senescence (CS) in age-related diseases (ARDs) is a quickly emerging topic in aging research. Our comprehensive data mining revealed over 250 genes tightly associated with CS. Using systems biology tools, we found that CS is closely interconnected with aging, longevity and ARDs, either by sharing common genes and regulators or by protein-protein interactions and eventually by common signaling pathways. The most enriched pathways across CS, ARDs and aging-associated conditions (oxidative stress and chronic inflammation) are growth-promoting pathways and the pathways responsible for cell-extracellular matrix interactions and stress response. Of note, the patterns of evolutionary conservation of CS and cancer genes showed a high degree of similarity, suggesting the co-evolution of these two phenomena. Moreover, cancer genes and microRNAs seem to stand at the crossroad between CS and ARDs. Our analysis also provides the basis for new predictions: the genes common to both cancer and other ARD(s) are highly likely candidates to be involved in CS and vice versa. Altogether, this study shows that there are multiple links between CS, aging, longevity and ARDs, suggesting a common molecular basis for all these conditions. Modulating CS may represent a potential pro-longevity and anti-ARDs therapeutic strategy.
细胞衰老（CS）在年龄相关性疾病（ARDs）中的作用是衰老研究中一个迅速兴起的话题。我们全面的数据挖掘揭示了超过250个与CS紧密相关的基因。使用系统生物学工具，我们发现CS与衰老、长寿和ARDs紧密相连，要么通过共享共同的基因和调节因子，要么通过蛋白质-蛋白质相互作用，最终通过共同的信号通路。在CS、ARDs和衰老相关条件（氧化应激和慢性炎症）中最富集的通路是促进生长的通路以及负责细胞-细胞外基质相互作用和应激反应的通路。值得注意的是，CS和癌症基因的进化保守模式显示出高度相似性，表明这两种现象共同进化。此外，癌症基因和微小RNA似乎处于CS和ARDs的交叉点。我们的分析还为新的预测提供了基础：癌症和其他ARDs共有的基因极有可能参与CS，反之亦然。总之，这项研究表明CS、衰老、长寿和ARDs之间存在多种联系，提示所有这些情况都有共同的分子基础。调节CS可能代表一种潜在的促进长寿和抗ARDs的治疗策略。
