Abstract

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.