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Common Signature of Longevity and ARDs

Network: H. sapiens miRNA-regulated interactome (H. sapiens)
The network was constructed using protein-protein interactions from BioGRID version 2.42 and documented miRNA targets from TarBase.

Experiment: 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.

Fig. 1. Schematic representation of the overlap between the human longevity network and the networks of major age-related diseases.
Fig. 2. Distribution of Common Signature Network proteins by basic processes. The proteins were classified using annotation from the human protein reference database (HPRD).
Fig. 3. Common signaling signature network (CSSN) of Human longevity and major age-related diseases. Presented are the proteins which connect at least two signaling pathways. Green circles represent longevity-associated proteins (LAPs). Red or grey circles represent non-LAPs. Large circles are hubs (nodes with >40 connections) and small circles are non-hubs. Solid lines connect pathways (white rectangles with the number of proteins in CSSN) through their common proteins. Dashed lines show the interactions between proteins.