The signaling hubs at the crossroad of longevity and age-related disease networks.
The established human age-related disease proteins (ARDPs) and longevity-associated proteins (LAPs) together with their first-order interacting partners form scale-free networks which significantly overlap. About half of the common proteins are involved in signal transduction. These proteins are strongly interconnected and in turn form a common signaling network which comprises over 40% of all hubs (proteins with multiple interactions) in the human interactome. Along with the insulin pathway, the common signaling network is remarkably enriched with the focal adhesion and adherens junction proteins whose relation to the control of lifespan is yet to be fully addressed. The examples of such candidate proteins include several hubs, focal adhesion kinase PTK2 and the extracellular proteins fibronectin FN1, paxillin PXN, and vinculin VCL. The results of the network-based analysis highlight the potential importance of these pathways, especially hubs, in linking the human longevity and age-related diseases.
Wolfson
Marina
M
The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, Center for Multidisciplinary Research in Aging, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel.
Budovsky
Arie
A
Tacutu
Robi
R
Fraifeld
Vadim
V
D022005:Adherens Junctions / Q000473:pathology / Q000502:physiology*; D000375:Aging / Q000473:pathology / Q000502:physiology*; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D022001:Focal Adhesions / Q000473:pathology / Q000502:physiology*; D006801:Humans; D008136:Longevity; D051419:Paxillin / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D015398:Signal Transduction; D016596:Vinculin / Q000378:metabolism
D005353:Fibronectins; D051419:Paxillin; D016596:Vinculin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human