Predicting aging/longevity-related genes in the nematode Caenorhabditis elegans.

We present a novel mathematical/computational strategy for predicting genes/proteins associated with aging/longevity. The novelty of our method arises from the topological analysis of an organismal longevity gene/protein network (LGPN), which extends the existing cellular networks. The LGPN nodes represent both genes and corresponding proteins. Links stand for all known interactions between the nodes. The LGPN of C. elegans incorporated 362 genes/proteins, 160 connecting and 202 age-related ones, from a list of 321 with known impact on aging/longevity. A 'longevity core' of 129 directly interacting genes or proteins was identified. This core may shed light on the large-scale mechanisms of aging. Predictions were made, based upon the finding that LGPN hubs and centrally located nodes have higher likelihoods of being associated with aging/longevity than do randomly selected nodes. Analysis singled-out 15 potential aging/longevity-related genes for further examination: mpk-1, gei-4, csp-1, pal-1, mkk-4, 4O210, sem-5, gei-16, 1O814, 5M722, ife-3, ced-10, cdc-42, 1O776Co, and 1O690.