# Impairment of Intrinsic Muscle Excitability in Aging

> **NIH NIH K02** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $140,508

## Abstract

Project Summary/Abstract
As life expectancy increases in the United States, age-related muscle dysfunction becomes a growing public
health concern. Declines in muscle power--the speed of muscle force development--limit mobility and increase
susceptibility to injury in older people. Power declines not only impact the quality of life of the individual, but
also place additional strain on families and the health care system. For this reason, a more profound
understanding of the aging process in skeletal muscle is critical for enabling Americans to remain active and
healthy later in life. Electromyography has shown that muscle conduction velocity decreases in older muscles,
raising the possibility that slower AP conduction velocity in single muscle fibers contributes to power decline.
Since voltage-gated Na+ channels are the principal molecular components of action potential initiation and
propagation in single muscle fibers, these channels present as targets to help preserve excitability and power.
Indeed, earlier studies have raised the possibility that changes in sarcolemmal/transverse-tubular Na+ channel
expression and/or gating properties underlie slowed action potential conduction velocity in aging muscle, but
the interpretation of these results has been confounded by the inherent limitations of conventional experimental
approaches. In Specific Aim 1, two-electrode voltage-clamp electrophysiology and non-invasive, alternating-
field optical action potential recordings will be used to test the hypothesis that altered Na+ channel gating
and/or expression underlie early age-dependent slowing of muscle actional potential conduction velocity. In
doing so, the applicant will gain expertise in two powerful, state-of-the-art techniques which have not previously
been used to investigate the impact of aging on muscle excitability. Alterations in Na+ channel gating and/or
expression will be tracked in both standard C57BL/6 and accelerated DBA2/J aging mouse models. Specific
Aim 2 will test the hypothesis that caloric restriction, an intervention which attenuates neuromuscular decline,
slows age-dependent impairment of action potential conduction velocity in both C57BL/6 and DBA2/J muscle
by delaying changes in Na+ channel expression/function. Alterations in Na+ channel isoform expression in both
C7BL/6 and DBA2/J muscle will be confirmed with immunoblotting. The performance of the work described in
Specific Aims 1 and 2 will thus broaden the applicant’s knowledge of aging biology through the introduction of
new aging models and the caloric restriction intervention into his research program. An K02 award will promote
the applicant’s development as an aging biologist by providing protected time to: 1) set the foundation for a
competitive NIA R01-level grant proposal, 2) build new collaborations with established aging scientists (both on
campus and at NIA-Bayview), and 3) to attend events focusing on aging/muscle biology and responsible
conduct in research.

## Key facts

- **NIH application ID:** 10300291
- **Project number:** 1K02AG071852-01A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Roger Alan Bannister
- **Activity code:** K02 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $140,508
- **Award type:** 1
- **Project period:** 2021-08-01 → 2022-03-27

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10300291

## Citation

> US National Institutes of Health, RePORTER application 10300291, Impairment of Intrinsic Muscle Excitability in Aging (1K02AG071852-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10300291. Licensed CC0.

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