# Cellular Mediators of Cardiac Aging and Arrhythmia in Drosophila

> **NIH NIH R21** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 2020 · $243,750

## Abstract

Summary
Atrial fibrillation affects 3-6 million people in the US. The risk of developing AFib and other cardiac arrhythmias
increases with age. Individuals over the age of 65 have a 9% chance of developing AFib with an increased risk
of stroke being the primary complication. Currently there are few options for treating AFib, primarily
anticoagulation therapy to prevent blood clots and medications to control heart rate but there is no “cure”.
There is evidence that common substrates link AFib with other types of arrhythmia and heart disease. For
example, the risk for AF is doubled in LQTS patients and the risk of TdP is much greater in patients with AF
when taking ion channel blockers suggesting that AF has an influence on the QT interval. We hypothesize that
homeostasis of the dynamic chromatin steady state (a process we have termed “chromostasis”) of heart
cardiomyocytes is critical for maintenance of an appropriate gene expression program, phenotype and function
at the cellular and tissue levels over the life span. Using the Drosophila cardiac model, we will identify gene
networks/cellular substrates for age-related arrhythmias based on age-dependent changes in transcriptomic
signatures. We will first obtain functional data on hearts from young and old wildtype and arrhythmogenic K+
channel mutant flies. Because we anticipate that epigenetic “drift” occurs over the lifespan and is manifest at
several levels we will identify transcriptomics changes in individual hearts with manifest arrhythmia and
between sub-regions of individual hearts that exhibit both normal and impaired function. Subsequent
bioinformatics analyses will allow us to identify genetic networks that are associated with arrhythmic cardiac
function. By comparing data from the wildtype and mutant fly lines at young and old ages, we will identify gene
networks that are common to both types of arrhythmia. We will subsequently screen top candidate genes as
well as genes previously identified in humans as being associated with AFib. The top hits from this screen will
be examined for their ability to suppress arrhythmias in old hearts and in hearts with K+ channel mutations.
Identification of the substrates for age-related arrhythmias will provide testable hypotheses that can be further
explored to establish targets for therapeutic intervention.

## Key facts

- **NIH application ID:** 9849707
- **Project number:** 5R21AG061598-02
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **Principal Investigator:** Karen Ocorr
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $243,750
- **Award type:** 5
- **Project period:** 2019-01-15 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849707

## Citation

> US National Institutes of Health, RePORTER application 9849707, Cellular Mediators of Cardiac Aging and Arrhythmia in Drosophila (5R21AG061598-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9849707. Licensed CC0.

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