# Cardioprotective role of Humanin in aging

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $469,811

## Abstract

Abstract
Aging is a risk factor for cardiovascular diseases. Coronary artery disease is the leading cause of death and
morbidity world-wide. Metabolic shifts and oxidative stress that occur in the myocardium during the phases of
ischemia as well as reperfusion cause myocardial injury and play a pivotal role in the development and
progression of myocardial damage and heart failure (HF). Humanin (HN), a novel small peptide generated by
mitochondria, has been shown to exhibit strong cytoprotection in many age-related diseases with increased
oxidative stress including Alzheimer’s disease, atherosclerosis, myocardial and cerebral ischemia, and type 2
diabetes. Our group has demonstrated that administration of HN results in a decrease in infarct size and
preservation of cardiac function in a mouse model of myocardial ischemia-reperfusion (MI-R) injury.
Additionally, our preliminary data presented in this grant submission shows that HN administration results in: 1)
infarct size reduction following MI-R injury in aging rodent and clinically-relevant porcine models of MI-R; 2)
improved cardiac function as evidenced by decreased end diastolic volume in old mice with myocardial
ischemia-induced heart failure; 3) increased peroxisomal fatty acid oxidation, and inhibition of mitochondrial
fatty acid oxidation in primary cardiomyocytes and heart lysates; 4) decreases ROS and 5) improved survival
of cardiomyocytes following hypoxia and oxidative stress. Based on these data, we hypothesize that HN
treatment will improve cardiac function in MI-R injury or MI induced heart failure (HF) through its unique ability
to induce metabolic adaptations in cardiac myocytes, improve peroxisomal function and decrease ROS,
thereby limiting acute myocardial cell death, and preventing the progression to HF. In this grant application, we
will delineate the cardioprotective efficacy of HN in murine models of MI-R injury and MI induced HF in aging
and elucidate the mechanisms that underlie HN’s cardioprotective effects on the myocardium. In an exploratory
sub aim, we will assess HN levels in heart and circulation in human subjects with post-ischemia cardiac failure.
Results from these experiments may potentially have a tremendous impact in treating cardiovascular diseases.
HN may provide a much-needed therapeutic option for patients to protect the myocardium from ischemic and
reperfusion injuries, and prevent the progression to HF.

## Key facts

- **NIH application ID:** 10490267
- **Project number:** 5R01AG069399-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Partha Dutta
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $469,811
- **Award type:** 5
- **Project period:** 2021-09-30 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10490267

## Citation

> US National Institutes of Health, RePORTER application 10490267, Cardioprotective role of Humanin in aging (5R01AG069399-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10490267. Licensed CC0.

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