# The regulation of health and longevity by branched-chain amino acids

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $454,774

## Abstract

Project Summary
 Age-related diseases are the major causes of morbidity and mortality in Western society. Calorie
restriction (CR), a dietary intervention which extends lifespan while delaying or preventing age-related disease,
is one plausible approach to lessen the burden of these diseases, but reduced-calorie diets are notoriously
difficult to sustain. Recent studies have highlighted an important role for dietary protein in health and longevity,
with low protein (LP) diets shown to promote longevity and to mimic the metabolic benefits of CR. We have
found that specifically reducing dietary consumption of the three branched-chain amino acids (BCAAs) –
leucine, isoleucine, and valine – promotes metabolic health in both young and aged mice, and promotes
longevity in progeroid mice. Determining the effect of Low BCAA diets on longevity, and identifying the
physiological and molecular mechanisms by which dietary BCAAs influence metabolism, will provide
mechanistic insight into the regulation of healthy aging. Eventually, this will permit the development of new
pharmacological approaches to prevent or delay age-related diseases.
 Here, we will rigorously test the hypothesis that a Low BCAA diet can promote health and longevity in
mice, examining the effect of long-term Low BCAA diet on lifespan, metabolic health, cardiac function and
frailty. We will determine if reduced consumption of the BCAAs mediates the metabolic effects of CR and LP
diets. Finally, we will examine the cell autonomous effects of the BCAAs and their catabolites on the function
and metabolism of primary hepatocytes and pancreatic islets ex vivo using novel metabolic sensors, and test
candidate molecular mediators of these effects.
 The proposed work will examine the role of the branched-chain amino acids on health and longevity for
the first time, and address long-standing questions regarding how dietary quality – the specific composition of
the diet – impacts healthy aging. Importantly, we will gain new insight into the physiological and molecular
mechanisms that drive the potent effects of CR and LP diets. In the long term, this work will enable our
laboratory and others to develop a mechanistic understanding of how dietary branched-chain amino acids and
other macronutrients regulate health and disease vulnerability, and to identify new targets for the
pharmacological treatment of age-related diseases and the promotion of healthy aging.

## Key facts

- **NIH application ID:** 9840434
- **Project number:** 5R01AG056771-03
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Dudley William Lamming
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $454,774
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840434

## Citation

> US National Institutes of Health, RePORTER application 9840434, The regulation of health and longevity by branched-chain amino acids (5R01AG056771-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9840434. Licensed CC0.

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