Report: NIA workshop on translating genetic variants associated with longevity into drug targets

To date, candidate gene and genome-wide association studies (GWAS) have led to the discovery of longevity-associated variants (LAVs) in genes such as FOXO3A and APOE. Unfortunately, translating variants into drug targets is challenging for any trait, and longevity is no exception. Interdisciplinary and integrative multi-omics approaches are needed to understand how LAVs affect longevity-related phenotypes at the molecular physiologic level in order to leverage their discovery to identify new drug targets. The NIA convened a workshop in August 2017 on emerging and novel in silico (i.e., bioinformatics and computational) approaches to the translation of LAVs into drug targets. The goal of the workshop was to identify ways of enabling, enhancing, and facilitating interactions among researchers from different disciplines whose research considers either the identification of LAVs or the mechanistic or causal pathway(s) and protective factors they influence for discovering drug targets. Discussions among the workshop participants resulted in the identification of critical needs for enabling the translation of LAVs into drug targets in several areas. These included (1) the initiation and better use of cohorts with multi-omics profiling on the participants; (2) the generation of longitudinal information on multiple individuals; (3) the collection of data from non-human species (both long and short-lived) for comparative biology studies; (4) the refinement of computational tools for integrative analyses; (5) the development of novel computational and statistical inference techniques for assessing the potential of a drug target; (6) the identification of available drugs that could modulate a target in a way that could potentially provide protection against age-related diseases and/or enhance longevity; and (7) the development or enhancement of databases and repositories of relevant information, such as the Longevity Genomics website (https://www.longevitygenomics.org), to enhance and help motivate future interdisciplinary studies. Integrative approaches that examine the influence of LAVs on molecular physiologic phenotypes that might be amenable to pharmacological modulation are necessary for translating LAVs into drugs to enhance health and life span.