# Translational analysis of a novel intervention to promote healthy aging.

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $659,916

## Abstract

Project Summary
 Advancing age is associated with an increased risk of type 2 diabetes, which is exacerbated by the high
prevalence of obesity in the aged. These disorders are risk factors for age-related diseases associated with
significant morbidity and mortality, including cancer, cardiovascular disease, and Alzheimer’s disease. New
approaches to maintain glucose homeostasis in the aged are therefore urgently needed.
 The objective of the proposed study is to test the ability of diets with reduced levels of isoleucine, valine,
or histidine to reverse diet induced obesity and insulin resistance. We have shown that specifically reducing
levels of either isoleucine, valine, or histidine can rapidly reduce adiposity in diet-induced obese mice, restoring
normal body composition and enhancing insulin sensitivity. Further, we have shown that diets with lower levels
of isoleucine or histidine are associated with reduced body mass index in humans.
 Here, we will determine the degree of restriction of these three amino acids that optimally promotes
metabolic health in diet-induced obese mice and test an optimized amino acid restricted diet for the ability to
reduce adiposity and restore glycemic control in a non-human primate. We will also gain insight into the molecular
mechanisms induced by reduced levels of these dietary amino acids through integrative transcriptomic and
metabolomic analyses of blood, adipose, and skeletal muscle samples from nonhuman primates and from young
and aged mice. Additionally, we will collect samples for future analysis of the role of the epigenome and
microbiome in the response to dietary amino acids. These studies are urgently needed to understand if
manipulation of specific dietary amino acids is a translatable intervention to promote metabolic health and
increase healthspan.

## Key facts

- **NIH application ID:** 10905341
- **Project number:** 1R01AG085898-01A1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** RICKI J COLMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $659,916
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10905341

## Citation

> US National Institutes of Health, RePORTER application 10905341, Translational analysis of a novel intervention to promote healthy aging. (1R01AG085898-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10905341. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*