# ACE2 as a novel therapeutic to preserve physical function in late life

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $213,098

## Abstract

ABSTRACT
Declining physical function and the onset of disability among older persons has a tremendous impact on the
health and longevity of affected individuals and is a central contributor to rising healthcare costs. Therapeutic
strategies for the preservation of physical function are currently limited. Preliminary evidence suggests that the
renin-angiotensin system (RAS) is a promising target for the development of new therapeutics to prevent
functional decline. However there is currently a lack of knowledge regarding the direct impact of a recently-
discovered vasodilatory arm of the RAS which is modulated primarily by the actions of the bioactive agent
angiotensin converting enzyme 2 (ACE2) to convert angiotensin I and II to angiotensin-(1-7). This project will
address this gap in knowledge by evaluating the impact of directly administering ACE2 to older rats in the
preservation of physical function. We hypothesize that direct pharmacologic activation of the ACE2 axis will
attenuate functional declines in late life. We will address this hypothesis with three specific aims, which are to:
1) Demonstrate that systemic administration of ACE2 improves physical function among older Fischer 344 x
Brown Norway (F344/BN) rats, 2) Demonstrate that ACE2 improves functional responses to physical exercise,
and 3) Identify physiologic adaptations associated with functional responses to ACE2 administration both in
isolation and in combination with exercise. ANTICIPATED IMPACT: We have designed this study so that it has
potential to be swiftly translated to humans. This study will fill an important gap in knowledge while also
providing important data for the subsequent design of human studies to test our central hypothesis. The study
is significant in that it addresses several clinical and public health problems deemed significant by the NIH as
well as an important gap in the scientific literature. Innovations in the project include the reverse translation of
our prior work in this area, targeting of the RAS for health benefits other than the regulation of blood pressure,
and methodological innovations in the delivery of the therapeutic compound and the use of matrix-assisted
laser desorption ionization (MALDI) mass spectrometry to evaluate tissue-level adaptations to the
interventions.

## Key facts

- **NIH application ID:** 10163758
- **Project number:** 5R01AG054538-05
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Thomas W Buford
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $213,098
- **Award type:** 5
- **Project period:** 2017-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163758

## Citation

> US National Institutes of Health, RePORTER application 10163758, ACE2 as a novel therapeutic to preserve physical function in late life (5R01AG054538-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10163758. Licensed CC0.

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