The signaling hubs at the crossroad of longevity and age-related disease networks

Int J Biochem Cell Biol. 2009 Mar;41(3):516-20. doi: 10.1016/j.biocel.2008.08.026. Epub 2008 Aug 29.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adherens Junctions / pathology
  • Adherens Junctions / physiology*
  • Aging / pathology
  • Aging / physiology*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Animals
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Fibronectins / metabolism
  • Focal Adhesion Kinase 1 / metabolism
  • Focal Adhesions / pathology
  • Focal Adhesions / physiology*
  • Humans
  • Longevity
  • Paxillin / metabolism
  • Protein Interaction Domains and Motifs
  • Signal Transduction*
  • Vinculin / metabolism

Substances

  • Fibronectins
  • Paxillin
  • Vinculin
  • Focal Adhesion Kinase 1
  • PTK2 protein, human