# Autonomous and Non-Autonomous Regulation of Cardiac Aging

> **NIH NIH R01** · IOWA STATE UNIVERSITY · 2020 · $302,392

## Abstract

Project Summary/Abstract
 Aging is associated with an exponential increase in the incidence of cardiovascular
diseases (CVD). Several mechanisms underlying age-associated cardiac changes in fly model
and vertebrates have been proposed, for example, decreased cellular quality control, altered
calcium handling, increased mitochondria damage, and the production of reactive oxygen species
(ROS). Cellular quality control systems, like autophagy, are essential protective mechanisms for
the maintenance of tissue homeostasis during cardiac aging. It is well-known that autophagy
declines with age. However, the molecular basis for age-dependent dysregulation of autophagy
and its contribution to cardiac homeostasis remain largely unknown.
 Our recent studies uncovered an exciting link between activin and mechanistic target of
rapamycin complex 2 (mTORC2) in the regulation of autophagy and cardiac aging. We also
noticed that two mTOR complexes (mTORC1 and mTORC2) seem to play distinct roles in
autophagy regulation. Furthermore, through genetic screening we identified several activin-
regulated systemic factors (e.g., Upd3, the fly homology of mammalian Interleukin 6, IL-6) that
can mediate tissue-tissue communication and maintain cardiac homeostasis. In this proposal, we
aim to dissect the distinct mechanisms by which activin signaling regulate autophagy and age-
dependent cardiac dysfunctions through the interactions with two important pathways, mTORC2
and JAK-STAT. To achieve the overall objective, we propose two specific aims. Specific Aim 1:
Determine how activin interacts with mTORC2 to regulate autophagy and cardiac aging; Specific
Aim 2: Determine the role of activin and Upd3 in oenocyte-heart communication during aging.
 The mechanistic understanding of the tissue specificity and the underlying function of
activin in cardiac aging will provide strong justification for its continued development as a novel
target for potential therapeutic intervention.

## Key facts

- **NIH application ID:** 9849708
- **Project number:** 5R01AG058741-02
- **Recipient organization:** IOWA STATE UNIVERSITY
- **Principal Investigator:** Hua Bai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $302,392
- **Award type:** 5
- **Project period:** 2019-01-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849708

## Citation

> US National Institutes of Health, RePORTER application 9849708, Autonomous and Non-Autonomous Regulation of Cardiac Aging (5R01AG058741-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9849708. Licensed CC0.

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