# Genetic variant-based drug discovery targeting conserved pathways of aging

> **NIH NIH U19** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2021 · $1,812,656

## Abstract

ABSTRACT - OVERALL
Aging is an important risk factor for most common human diseases, including type 2 diabetes, cardiovascular
disease, cancer and neurodegeneration. In the proposed collaborative U19 proposal, we will test a new
approach for developing therapies for these diseases. Rather than focusing on individual diseases, we will
explore genetic differences between successfully aged, healthy centenarians and control individuals with no
family history of extreme longevity. Based on our own preliminary results, many of such genetic differences
affect loci known to be involved in extreme longevity and health span in model organisms, such as worms and
mice. Using the centenarian resource at the Albert Einstein College of Medicine, we will identify rare genetic
variants and microRNAs associated with conserved mechanisms of healthy longevity as potential targets, for
drug discovery (Project 1), evaluate these variants or associated pathways functionally in mouse models of
aging, including natural aging, for phenotypes relevant for late-life human health (Project 2), and subsequently
use them as leads for developing and testing small molecules targeting the pathways affected by these rare
variants and miRNAs (Project 3). This integrated research project will be supported by two cores: an
Administrative Core to coordinate the research (Core A) and a Genetically Engineered Mouse and
Geropathology Core (Core B). Using our extensive genetic resources, including some from our pharmaceutical
partner, Regeneron, we also will confirm further and validate some of the genetic variants and discover
additional, novel genetic variants and associated pathways important for human longevity. The proposed
project should greatly increase our understanding of the importance of the conserved pro-longevity pathways,
identified and thus far mostly studied in model organisms, for human aging. Importantly, this gene to drugs
collaborative project will be the first to use the genetics of rare individuals with healthy aging as a guide for the
development of therapeutic approaches for targeting aging itself rather than its composite diseases for
preventing, delaying onset and progression, and possibly even reverting many multiple age-related diseases.

## Key facts

- **NIH application ID:** 10173582
- **Project number:** 5U19AG056278-06
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** JAN VIJG
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,812,656
- **Award type:** 5
- **Project period:** 2017-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10173582

## Citation

> US National Institutes of Health, RePORTER application 10173582, Genetic variant-based drug discovery targeting conserved pathways of aging (5U19AG056278-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10173582. Licensed CC0.

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