Budovsky Arie, Tacutu Robi, Yanai Hagai, Abramovich Amir, Wolfson Marina, Fraifeld Vadim
The Shraga Segal Department of Microbiology and Immunology, Center for Multidisciplinary Research in Aging, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Mech Ageing Dev. 2009 Jan-Feb;130(1-2):33-9. doi: 10.1016/j.mad.2008.04.002. Epub 2008 Apr 12.
An association between aging/longevity and cancer has long been suggested, yet the evolutionary and molecular links between these complicated traits remain elusive. Here, we analyze the relationship between longevity- and cancer-associated genes/proteins (LAGs/LAPs and CAGs/CAPs, respectively). Specifically, we address the following questions: (1) to what extent the CAGs and LAGs are evolutionary conserved and how they (or their orthologs) are related to each other in diverse species? (2) Could they act in cooperative manner at a protein level via protein-protein interactions (PPIs) and, if so, by forming a PPI network? We found that (i) the common genes (both LAGs and CAGs) show the same remarkable trend from yeast to humans: tumor suppressors are associated with lifespan extension, whereas the oncogenes are associated with reduced lifespan; (ii) LAPs and CAPs have a significantly higher average connectivity than other proteins in the human interactome; and (iii) LAPs and CAPs may act in cooperative manner via numerous direct and indirect PPIs between themselves and eventually by forming a PPI network. Altogether, the results of this study provide strong evidence for the existence of evolutionary and molecular links between longevity and cancer.
衰老/长寿与癌症之间的关联早已被提出，但这些复杂性状之间的进化和分子联系仍不清楚。在此，我们分析了与长寿和癌症相关的基因/蛋白质（分别为LAGs/LAPs和CAGs/CAPs）之间的关系。具体而言，我们探讨以下问题：（1）CAGs和LAGs在多大程度上是进化保守的，以及它们（或其直系同源物）在不同物种中彼此之间是如何关联的？（2）它们能否在蛋白质水平上通过蛋白质-蛋白质相互作用（PPI）以协同方式发挥作用，如果是这样，是否通过形成PPI网络？我们发现：（i）共同基因（LAGs和CAGs）从酵母到人类呈现出相同的显著趋势：肿瘤抑制因子与寿命延长相关，而癌基因与寿命缩短相关；（ii）在人类相互作用组中，LAPs和CAPs的平均连接性显著高于其他蛋白质；（iii）LAPs和CAPs可能通过它们之间众多直接和间接的PPI以协同方式发挥作用，并最终形成一个PPI网络。总之，本研究结果为长寿与癌症之间存在进化和分子联系提供了有力证据。
