# Integrative Cross Species Analysis for Longevity Drug Target Identification

> **NIH NIH UH3** · TRANSLATIONAL GENOMICS RESEARCH INST · 2024 · $390,000

## 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 l...

## Key facts

- **NIH application ID:** 11144139
- **Project number:** 3UH3AG064706-05S1
- **Recipient organization:** TRANSLATIONAL GENOMICS RESEARCH INST
- **Principal Investigator:** RICHARD A MILLER
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $390,000
- **Award type:** 3
- **Project period:** 2019-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11144139

## Citation

> US National Institutes of Health, RePORTER application 11144139, Integrative Cross Species Analysis for Longevity Drug Target Identification (3UH3AG064706-05S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/11144139. Licensed CC0.

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