For a study conducted by the Buck Institute for Age Research, a longevity protein network was assembled from a large-scale interaction map developed at Prolexys Pharmaceuticals in Salt Lake City, UT. The longevity network consists of 3,271 interactions among 2,338 different proteins, including 175 equivalent human versions of proteins that influence life span in yeast, nematode worms or flies, and 2,163 additional human proteins that interact with those proteins. Researchers found that there is a complex web of interactions among the human equivalents of the many longevity genes found in simple animals. The results revealed a “surprisingly close relationship between aging processes in humans and simpler organisms.”
Robert E. Hughes, a faculty member of the Buck Institute and lead author of the study, pointed out that although there have been hundreds of longevity-related genes identified in such simple animals as worms, flies and yeast, “There has always been a question of how relevant those genes are to humans. This really demonstrates that there’s a strong relationship between the kinds of genes that appear to be important in human aging at the level of protein interaction and changes in gene expression and the kinds of genes that have been identified in large-scale genetic screens in invertebrate species,” he says. “This establishes a similarity in the aging process among diverse species that is perhaps a lot broader than many of us may have expected.”
One dramatic result of analyzing the network was the finding that the longevity proteins had an average of 19 connections. This is compared to an average of 14 for proteins in general. Hughes noted that these longevity proteins function as “hubs” or interfaces among groups of proteins and that removing the highly connected hub genes may possibly increase life span by “preventing dysfunctional events from spreading through the cell.” The study also found that “the network was enriched for proteins encoded by genes whose expression levels change during human aging,” further proof of the link between human and invertebrate aging.
Dr. Sudhir Sahasrabudhe, Chief Scientific Officer and the scientific founder of Prolexys Pharmaceuticals, notes that “this work demonstrates the value of combining high-throughput screening for protein interactions with genetic and functional validation to understand complex biological processes such as aging. Furthermore, we would like to encourage scientists interested in aging and longevity to mine the data made available in the study,” he says. The Prolexys human interactome database – the largest of its kind in the world – contains over 120,000 non-redundant protein interactions and represents approximately one half of all RefSeq entries.
News Release: Aging: Worms, flies and yeast are more like us than previously expected www.newswise.com March 9, 2009
