We know that aging is influenced by how genetic and environmental factors interact, with genetics contributing substantially to healthy aging and exceptional longevity in people in current environments.
Today we have new opportunities to study these genetic factors, spurred by new initiatives in NIA’s Division of Geriatrics and Clinical Gerontology. We have developed a research program on the translation of genetic factors associated with longevity, giving us the chance to translate these insights into new therapeutic targets to promote healthy aging. The hope is to use the insight from genetics to develop a drug or other intervention that can mimic the effect of a favorable variation.
Translational genomics—intervention development based on target identification of genetic variants—has been used successfully in cancer and cardiovascular diseases. This success can be partly attributed to understanding the role of genetic factors in the biological pathways associated with the disease processes. In aging, new targets could be identified based on knowledge of the functional pathways of the gene variants associated with longevity. Because longevity is associated with reduced risk for a wide range of diseases and conditions, any targets identified could help protect against several age-related conditions, instead of just a single disease. (See this previous post for more information.)
What is the status of translational genomics for healthy aging?
Progress in translation of these protective variants has been slow and minimally successful. This is largely because we don’t understand the functional pathways and mechanisms by which these gene variants exert their protective effects. So, the first step in the translational genomic process for healthy aging should be to unravel the biological pathways associated with the genes that protect against age-related diseases and enhance lifespan. The interplay of bio-regulatory factors also needs to be unraveled so we can develop functional outcomes for any resulting interventions.
What are available research resources and funding opportunities?
Longevity Consortium – A major emphasis of the NIA-supported Longevity Consortium (LC) is to translate findings from genomics and genetic epidemiology into interventions that promote healthy aging. Of the many gene variants reported to be associated with exceptional longevity in people, only FOXO3A and APOE2 have been replicated as protective variants in several population cohorts. The LC has two working groups involved in the translation of FOXO3A and APOE2. The LC is looking for collaborators and limited funding is available through the LC Translational Opportunity Funds to conduct pilot analyses or functional studies of genetic variants associated with human longevity. You can find details on working with the LC here: http://wp.longevityconsortium.org/funding-opportunities.
NIA PAR-15-175 – “Phenotypic and Functional Studies on FOXO3 Human Longevity Variants to Inform Potential Therapeutic Target Identification Research.” DGCG is supporting an R01 funding opportunity for the translation of FOXO3 using in vivo human studies and in vitro studies on human cells or tissues. The goal is to identify additional therapeutic targets upstream, as well as downstream regulators in pathways mediated by FOXO3. Full details are available at: http://grants.nih.gov/grants/guide/pa-files/PAR-15-175.html.
Research infrastructure for target-identification strategies
A recently funded NIA project involves a multidisciplinary collaborative team based at California Pacific Medical Center in San Francisco and headed by Dr. Steve Cummings (www.longevitygenomics.org). The goal is to develop target-identification strategies based on effects of genetic factors associated with increased longevity and health. By “target-identification strategies” we mean any and all ways to use the genetic signal to identify the molecular paths that could become the target of intervention. An important goal of the program is to establish an online database with genetic information from multiple population cohorts and findings from NIH-supported analyses. We expect that this database will facilitate the public use of genetic data for translational purposes.
If you would like to learn more or discuss specific research ideas related to translational genomics, please contact me at Nraghavachari@mail.nih.gov.