title: Molecular links between cellular senescence, longevity and age-related diseases - a systems biology perspective.
abstract: 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.
authors.affiliation: The Shraga Segal Department of Microbiology and Immunology, Center for Multidisciplinary Research on Aging, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Robi
authors.initials: R
authors.lastname: Tacutu
authors.forename: Arie
authors.initials: A
authors.lastname: Budovsky
authors.forename: Hagai
authors.initials: H
authors.lastname: Yanai
authors.forename: Vadim E
authors.initials: VE
authors.lastname: Fraifeld
mesh_terms: D000544:Alzheimer Disease; D050197:Atherosclerosis; D016922:Cellular Senescence / Q000502:physiology*; D002908:Chronic Disease; D019295:Computational Biology; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007249:Inflammation; D008136:Longevity / Q000502:physiology*; D035683:MicroRNAs; D009369:Neoplasms; D018384:Oxidative Stress; D060066:Protein Interaction Maps; D015398:Signal Transduction; D049490:Systems Biology
chemical_list: D035683:MicroRNAs