# Alteration of kynurenine pathway in age-associated muscle weakness

> **NIH NIH K08** · JOHNS HOPKINS UNIVERSITY · 2020 · $171,720

## Abstract

PROJECT SUMMARY
 Decline in skeletal muscle function with aging is a major determinant of disability and morbidity in late life.
However, the neurobiology of such decline in skeletal muscle function in normal aging is poorly understood.
The proposed K08 project is a critical step towards to understanding the underlying mechanism of age-related
decline of skeletal muscle function. This study uniquely focuses on the intersection between kynurenine
metabolic pathway, motor neuron, neuromuscular junction (NMJ), and skeletal muscle function. Kynurenine
pathway is a major route to the synthesis of Nicotinamide adenine dinucleotide (NAD), a critical coenzyme that
balances redox status of all living cells. Many intermediate metabolites of kynurenine pathway are known to be
potent neurotoxins, and involved in various age-related neurodegenerative diseases. The preliminary studies
of this project showed alterations of kynurenine pathway in aging peripheral neuromuscular system. Herein, it
is hypothesized that age-related alterations in kynurenine pathway contributes to neurodegeneration in spinal
motor neurons, eventually causing age-associated muscle weakness. Aim1 propose to identify key alterations
in the kynurenine pathway in the aging spinal motor neurons, using mass spectrometry, PCR, and Western
blot techniques. Aim2 propose to determine the neurotoxicity of kynurenine pathway in aging neuromuscular
system both in vitro and in vivo models. Finally, Aim3 tests the effects of pharmacological inhibition of a
kynurenine metabolite synthesis. The findings from this study will likely identify molecular targets for age-
associated muscle weakness, and used for future translational study.
 The proposal will take place in the Johns Hopkins School of Medicine under the mentorship of Jeremy
Walston, MD, Ahmet Hoke, MD, PhD, and Robert Schwarcz, PhD. An integrated career development and
mentoring plan has been also proposed to ensure Dr. Chung’s successful transition to independence. The
training goals are focused on development of Dr. Chung’s expertise in kynurenine neurobiology, various
molecular techniques in neuroscience research, and translational gerontology. The strength of the proposal
comes from the collaboration between all of his mentors who have world-renowned expertise in aging frailty
(Dr. Walston), peripheral neurodegeneration (Dr. Hoke), and kynurenine neurobiology (Dr. Schwarcz).

## Key facts

- **NIH application ID:** 9895596
- **Project number:** 5K08AG058483-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Tae Hwan Chung
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $171,720
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895596

## Citation

> US National Institutes of Health, RePORTER application 9895596, Alteration of kynurenine pathway in age-associated muscle weakness (5K08AG058483-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9895596. Licensed CC0.

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