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Integrative Omics to Enhance Therapeutics Development for Healthy Aging

There is a strong relationship between exceptional longevity and exceptional health span. For example, centenarians show delayed onset of age-related disabilities and morbidities such as cardiovascular disease and Alzheimer's disease. These findings are consistent with the concept that aging mechanisms influence both longevity and the development of multiple age-related conditions. Identifying factors that influence such mechanisms could facilitate the identification of interventions to enhance human health span. To develop such interventions, there is a need to identify therapeutic targets and assess the effects of engaging these targets.

GWAS analyses of exceptional longevity and healthy aging in humans have identified several variants associated with longevity and health span. These can serve as a starting point for efforts to identify therapeutic targets. However, strategies based on genetics alone have substantial limitations. Many gene products have multiple targets that interact with each other and with multiple genes. The relationships of genetic variants to expression profiles of RNA, proteins, and metabolites that influence longevity and health are complex. Thus, there is a need for multi-omics/integrative approaches (i.e., omics profiles) which could yield better predictors of healthy aging phenotypes than can be found based simply on individual gene variants, as well as guide the assessment of drugs targeted at specific molecules. In addition, to distinguish between factors that affect only one aging-related condition or have opposing effects on differing conditions vs. factors with more consistently beneficial effects, there is a need for phenomic approaches to assess the relationship of genetic factors and omics profiles to a wide range of aging-related outcomes. Studies on species with widely varying life spans also suggest that comparative omics approaches could yield insights into crucial factors influencing life span and health span. There is a need to integrate such approaches with human studies to enhance strategies to find potential targets for human interventions.

The proposed initiative will address the above needs. It will identify omics profiles associated with protection against multiple aging conditions and with exceptional health span, and refine strategies for utilizing these profiles in therapeutics development. Specifically, it will support multiple omics measurements (e.g., transcriptomics, proteomics, metabolomics) from the same individual and from multiple tissues from extensively phenotyped cohorts with substantial numbers of long-lived individuals and controls. It will also:

  • harmonize and extend phenotypic data from these studies to apply phenomics to transcriptomic, proteomic, and metabolomic findings;
  • select species or strains with varying life spans for comparative omics studies and identify potential determinants of species differences in longevity and rates of disease development;
  • develop appropriate computational and analytical tools to identify omics profiles associated with exceptional longevity and healthy aging;
  • apply informatics drug screening tools and other databases to identify molecules that could produce profiles associated with exceptionally healthy aging; and
  • exchange and harmonize data with related omics activities such as AMP-AD and other public-private partnerships.

This initiative is timely because of the advent of technologies that enable the collection and integration of large omics data sets including genome, transcriptome, proteome, metabolome and phenome. This type of integrative approach could identify crucial profiles that reveal connections between biological pathways and thereby enhance therapeutic development.

Please email Nalini Raghavachari, Ph.D., with any questions about this RFA.

Pre-Application Webinar

A webinar provided prospective applicants the opportunity to receive information and ask questions about the scientific scope of this announcement and technical details for applying. The webinar was held August 13, 2018, 3:00-4:30 p.m. ET. Access a recording of the webinar here. (Presentation starts at minute eight.)

Scientific/Research Contacts

Nalini Raghavachari, Ph.D.
Division of Geriatrics and Clinical Gerontology
National Institute on Aging
Telephone: 301-435-3048
E-mail Nalini Raghavachari, Ph.D.

Max Guo, Ph.D.
Division of Aging Biology
National Institute on Aging
Telephone: 301-402-7747
E-mail Max Guo, Ph.D.

Suzana Petanceska, Ph.D.
Division of Neuroscience
National Institute on Aging
Telephone: 301-496-9350
E-mail Suzana Petanceska, Ph.D.