A First Glance at the Gene Networks of Human Aging

Scientists have rendered the first gene and protein networks of human aging, an important step in understanding the genetic mechanisms of aging. The work led by Joao Pedro de Magalhaes from Harvard Medical School is detailed in the July 30 issue of FEBS Letters.

The work involved the integration of all genes, in both humans and animal models, previously shown to influence aging. By using a combination of bibliographic information and modern high-throughput genomics, employing software developed by the team, each gene was placed in the context of human biology. The putative impact of each gene to human aging was calculated by a combination of manual and computational methods, leading to a new holistic view of the genetics of aging. To organize and catalog all the data pertaining the over 200 genes selected, the first curated database of genes related to human aging was developed: GenAge, part of the Human Ageing Genomic Resources also led by Dr. de Magalhaes. Thanks to the help of many other researchers, the Human Ageing Genomic Resources have become, in months, the landmark online website for research on aging, having been recently featured in Nature Reviews Genetics (volume 5, issue 5, page 330) and SAGE KE (2004 volume, issue 30, nf69), Science Magazine’s website on aging research.

With the collaboration of researchers from the University of Namur in Belgium, scientists also analyzed protein-interaction maps for more specialized pathways previously linked with aging, such as the neuroendocrine regulation of aging and DNA metabolism. These findings and the rendered networks related to aging may prove useful to find novel genes of interest. In fact, several crucial nodes in the networks were identified by way of specialized software: a number of genes so far not linked to aging were chosen by a “guilt-by-association” methodology based on protein-protein interaction maps and data-mining algorithms. One intriguing finding was the apparent overlap between the genetics of aging and development. Aging could then be an indirect result of developmental pathways. The cascade of events that regulates ontogeny would then fade away after sexual maturity resulting in aging. Contrary to other theories of aging that argue aging derives from the accumulation of damage, Dr. de Magalhaes suggests that integrative pathways collaborate during development and then become disrupted during aging.

The GenAge database will be in constant development since several genes involved in aging are certainly yet to be identified. Even so, it provides an overview of the current state-of-the-art knowledge on human aging. While much works remains to fully understand aging, this is a major first step in understanding the genetic mechanisms of human aging and provides a framework for future experimental verification.