# Microbiome Metabolite Valerobetaine: Mechanisms in Aging

> **NIH NIH R21** · EMORY UNIVERSITY · 2023 · $430,375

## Abstract

Project Summary
Microbiome Metabolite Valerobetaine: Mechanisms in Aging
Obesity is increasing rapidly in the US and accumulating research shows that obesity accelerates the pace of
aging phenotypes related to mitochondrial dysfunction, nutrient sensing, intercellular communication and
inflammation and other characteristics. Intestinal microbiome is known to contribute to both obesity and aging
phenotypes, but mechanisms remain poorly defined. We recently found that a microbiome metabolite, delta-
valerobetaine (VB), disrupts carnitine-dependent mitochondrial fatty acid metabolism and causes increased
adiposity in young mice fed a Western diet. This is especially of interest because dysfunction of carnitine-
dependent mitochondrial fatty acid metabolism occurs with aging and is a common feature of many age-related
diseases. Additionally, carnitine supplementation, mostly in the more bioavailable form of acetylcarnitine
(ALCAR), is known to protect against age-related decline in mitochondrial structure and function. This raises
the possibility that microbiome production of VB causes or contributes to both obesity and mitochondrial aging
and antagonizes beneficial effects of carnitine or ALCAR. We have designed this high-risk, high-gain proposal
to address two aims, to determine whether VB promotes a mitochondrial aging phenotype in old mice and to
test whether VB antagonizes beneficial effects of carnitine (ALCAR) on mitochondrial aging. Studies are
designed with experimental variations in old female and male mice with control mouse diet and Western diet
and compared to the same manipulations in young mice of both sexes. Primary outcome measures are
focused on VB effects on mitochondrial functions and carnitine-dependent fatty acid metabolism. The aims are
developed with recognition that multiple factors contribute to mitochondrial and other aging phenotypes, and
that diet and microbiome effects are unlikely to be limited to one microbiome-derived metabolite. Specifically, if
adiposity and aging are consequences of agricultural successes in providing high nutritional quality feed stock
and more abundant essential amino acids, including lysine, methionine and tryptophan, in the human diet, then
VB effects will co-occur with other effects. For instance, VB is derived from a methylated form of lysine, which
may be potentiated by methionine, one of the key amino acids in nutrient sensing. Similarly, VB effects may
co-occur with microbiome metabolites of tryptophan which have been linked to intercellular signaling and
inflammation, or branched chain amino acid metabolites which have been linked to insulin resistance.
Because of these possibilities, the study is designed with additional measures of inflammation and
senescence, along with global metabolomics and transcriptomics analyses to test for associations with other
diet- and microbiome-linked metabolites. The results will have sustained impact on aging and age-related
disease research by providing...

## Key facts

- **NIH application ID:** 10763615
- **Project number:** 1R21AG080247-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Young-Mi Go Kang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $430,375
- **Award type:** 1
- **Project period:** 2023-09-30 → 2026-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10763615

## Citation

> US National Institutes of Health, RePORTER application 10763615, Microbiome Metabolite Valerobetaine: Mechanisms in Aging (1R21AG080247-01A1). Retrieved via AI Analytics 2026-06-25 from https://api.ai-analytics.org/grant/nih/10763615. Licensed CC0.

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