Integrative Omics to enhance therapeutics development for healthy aging

Information

  • Research Project
  • 10017120
  • ApplicationId
    10017120
  • Core Project Number
    UH2AG064706
  • Full Project Number
    5UH2AG064706-02
  • Serial Number
    064706
  • FOA Number
    RFA-AG-19-011
  • Sub Project Id
  • Project Start Date
    9/15/2019 - 4 years ago
  • Project End Date
    8/31/2021 - 2 years ago
  • Program Officer Name
    GUO, MAX
  • Budget Start Date
    9/1/2020 - 3 years ago
  • Budget End Date
    8/31/2021 - 2 years ago
  • Fiscal Year
    2020
  • Support Year
    02
  • Suffix
  • Award Notice Date
    8/27/2020 - 3 years ago

Integrative Omics to enhance therapeutics development for healthy aging

ABSTRACT/SUMMARY A number of drugs and interventions have been identified that curb morbidities associated with individual age- related diseases, and a few compounds have been identified that increase longevity in mice and other non- human species. However, few, if any, have been definitively shown to work by slowing the aging process and thereby simultaneously delaying the onset of multiple diseases and ultimately extending human longevity. Thus, current searches for drug and intervention targets that can lead to the development of longevity- enhancing `geroprotectors,' i.e., interventions which stave off multiple age-related diseases and increase longevity by slowing or disrupting aspects of the aging process, need to be improved. Only very integrated approaches are likely to lead to successful searches given the need to reconcile complexities surrounding the pathogenesis of age-related diseases with processes contributing to the synchronized decay of multiple systems that defines aging. We believe that such integration can be achieved practically by: 1. pursuing multiple human longitudinal studies focusing on the discovery of metabolites and proteins associated with a biologically-compelling definition of slow and healthy human aging in different tissues; 2. exploiting novel cross- species longevity studies involving multiple tissues to obtain insights into conserved pathways impacting longevity whose elements may be consistent with factors discovered in human studies and hence validate them as truly related to longevity and not just disease; and 3. aggregating data arising from items 1-2 along with relevant available public domain data to generate/validate hypotheses, in addition to pursuing a GWAS to identify protective factors for disease and using novel statistical and inferential methods. Our proposed studies are some of the first to champion the notion that the `triangulation' of disparate scientific studies and discoveries, i.e., the attempt to unify results from different study designs based on their biological coherence, is the optimal way to advance identification of human targets for longevity-enhancing geroprotective drugs and interventions. Importantly, although we believe that each of the individual studies we are proposing is itself powerful enough to identify potential geroprotector targets, their collective and integrated use with novel analytic methods will have unprecedented power and provide a paradigm for anti-aging drug discovery research within the academic community. For example, we are proposing the first human longitudinal study to search for druggable factors associated with the epigenetic clock and other validated measures of the aging rate/healthy aging in thousands of individuals; the largest metabolomics and proteomic cross-species multi- tissue study (N=60 species) of factors associated with lifespan; the largest human longitudinal comparative tissue study of aging exploring blood, muscle, fat and skin samples; and the largest study of aggregated data from public domain sources for association analyses including standard GWAS and a unique polygenic risk score-based healthy genome GWAS.

IC Name
NATIONAL INSTITUTE ON AGING
  • Activity
    UH2
  • Administering IC
    AG
  • Application Type
    5
  • Direct Cost Amount
    522256
  • Indirect Cost Amount
    81041
  • Total Cost
    603297
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    866
  • Ed Inst. Type
  • Funding ICs
    NIA:603297\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    ZAG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    TRANSLATIONAL GENOMICS RESEARCH INST
  • Organization Department
  • Organization DUNS
    118069611
  • Organization City
    PHOENIX
  • Organization State
    AZ
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    850042274
  • Organization District
    UNITED STATES