# Atrial Fibrillation in Aging Heart: Role of Senescent Atrial Cells

> **NIH NIH R21** · RHODE ISLAND HOSPITAL · 2022 · $260,517

## Abstract

The most common arrhythmia in the aging population is atrial fibrillation (AF), which carries an estimated
lifetime risk of 25% after the age of 40 years. Cellular senescence is a stress response that is characterized by
an irreversible loss of proliferative capacity, accompanied by a complex senescence-associated secretory
phenotype (SASP) that can have profound effects on neighboring cells in the tissue. Our research plan is
based on the following premises: Cellular senescence of atrial myocytes (AMs) and atrial cardiac fibroblasts
(ACMFs) plays an important role in fibrosis, inflammation and arrhythmogenesis. The overarching hypothesis
of our proposal is that atrial cell senescence is an important component of atrial aging and the increase
incidence of AF. Specifically, we postulate that in the aging human (and rabbit) atrium, the interplay between
aging and senescent AMs that have a lower threshold for arrhythmogenic activity and together with senescent
ACMFs leads to fibrosis and the triggering of AF. This R21 proposal brings together several investigators with
very different expertise to investigate mechanisms of AF in the aging heart, using a novel age-appropriate
large animal model (rabbit), and human samples obtained from explanted hearts and right atrial appendage. In
Aim 1 the Koren group will investigate the aging rabbit atria, as compared to the young atria, and correlate the
arrhythmogenesis with molecular and cellular analysis of AMs and ACMFs. Senescence will be manipulated in
vivo under Aim1 using pharmacologic approaches. Optical mapping of hearts ex vivo will be used to study
arrhythmogenesis. In Aim 2 the group will study human explanted atria as well as tissue and AMs obtained
from right atrial appendages during open heart surgery. In summary, we envision that by understanding the
aging mechanisms that control cellular senescence we will be able to reduce fibrosis and the incidence of AF.

## Key facts

- **NIH application ID:** 10345318
- **Project number:** 1R21AG075118-01
- **Recipient organization:** RHODE ISLAND HOSPITAL
- **Principal Investigator:** GIDEON KOREN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $260,517
- **Award type:** 1
- **Project period:** 2022-09-30 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10345318

## Citation

> US National Institutes of Health, RePORTER application 10345318, Atrial Fibrillation in Aging Heart: Role of Senescent Atrial Cells (1R21AG075118-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10345318. Licensed CC0.

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