# Project 3: Systems Biology Multi-Omic Studies Of Healthy Aging In Companion Dogs

> **NIH NIH U19** · UNIVERSITY OF WASHINGTON · 2021 · $568,879

## Abstract

PROJECT 3: SYSTEMS BIOLOGY MULTI-OMIC STUDIES OF HEALTHY AGING IN COMPANION DOGS
ABSTRACT
Aging is an extremely complex phenotype, involving many genes and a large array of environmental factors.
Moreover, these determinants of aging do not operate independently but rather interact through a complex and
highly intertwined web of molecular processes and functional pathways. To fully understand how genetic and
environmental variation lead to variation in aging and age-related disease, one must therefore incorporate
these processes and pathways to create a more comprehensive, biologically realistic genotype-environment-
phenotype map. Until now, genome-wide association studies in human populations have explained little of the
substantial natural variation in lifespan and other age-related phenotypes. This Project aims to address this
challenge, using the companion dog as a powerful new model of aging, and focusing on several key
mechanisms linking genetic and environmental factors to aging phenotypes. Specifically, three key biological
domains — the metabolome, the microbiome, and the epigenome — will be explored in a set of three
complementary Specific Aims. Preliminary work by the investigators, whose combined expertise spans all
three domains, and by other researchers, suggests that these domains represent important functional layers
through which genetic and environmental variation shapes downstream phenotypic variation in aging and in
age-related disease. To systematically characterize the role of these intermediate functional layers, each of the
three domains will be rigorously assayed on an unprecedented scale, using state-of-the-art high-throughput
`omic' technologies. By combining data from each -omic domain with ancillary information on genetic,
environmental, and age-related phenotypic variation, and working closely with the other Cores and Projects of
this P01, this Project will identify molecular elements that are affected by genetic and environmental factors,
and which, in turn, are associated with age-related phenotypes. Such analyses will pinpoint specific functional
pathways connecting genetic and environmental variation to phenotypic variation in aging. Finally, in a fourth
Specific Aim, all three -omic domains will be integrated using novel systems biology and network-based
approaches to construct a comprehensive, predictive, multi-omic model of aging in natural populations. Notably,
this Project's focus on functional domains and the proposed multi-omic, systems level analysis, go far beyond
classical genotype-phenotype associations, mapping functional pathways through which genetics and
environment impact aging. Combined, the four Specific Aims of this project will therefore not only facilitate the
discovery of new aging biomarkers, but will also provide an improved mechanistic understanding of the aging
process, ultimately leading to an analytical, clinically relevant model that can improve prediction, diagnosis,
treatment, and ...

## Key facts

- **NIH application ID:** 10213630
- **Project number:** 5U19AG057377-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Daniel Edward Promislow
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $568,879
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213630

## Citation

> US National Institutes of Health, RePORTER application 10213630, Project 3: Systems Biology Multi-Omic Studies Of Healthy Aging In Companion Dogs (5U19AG057377-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10213630. Licensed CC0.

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