Non-Autonomous Regulation of Cardiac Aging

/Abstract Among all classes of phospholipids, ether phospholipids (mainly plasmalogens) have recently emerged as a novel regulator of mitochondrial membrane dynamics and animal aging. Plasmalogen deficiency has been linked to impaired mitochondrial dynamics, respiratory disorders, cardiomyopathy, and Alzheimer’s disease. The levels of plasmalogens in the circulation and animal brain decrease with age. However, the exact mechanisms underlying age-related reduction in plasmalogen biosynthesis and plasmalogen-regulated tissue homeostasis are largely unknown. Our recent studies identify the kidney as the site of plasmalogen biosynthesis and the source of circulating plasmalogens. Inhibition of kidney plasmalogen biosynthesis increases the production of inflammatory cytokines and cardiomyopathy. In contrast, plasmalogen supplements rescue cardiac defects in plasmalogen biosynthesis mutants. These findings suggest a previously unappreciated role of plasmalogen in kidney-heart communication. In this renewal application, we aim to take multi-disciplinary approaches to interrogate the novel role of kidney-derived plasmalogen ether phospholipids in inter-tissue communication and cardiac aging. Four specific aims are proposed: Aim 1. Determine the mechanisms underlying age-associated decreases in kidney plasmalogen biosynthesis. Aim 2. Determine how plasmalogens are transported from the kidney to the heart. Aim 3. Determine how kidney-derived plasmalogens regulate cardiac contractile performance. Project Number: 1R01AG095170-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Hua Bai (+1 co-PI) | Institution: IOWA STATE UNIVERSITY, AMES, IA | Award Amount: $523,313 | Activity Code: R01 | Study Section: Special Emphasis Panel[ZRG1 CDB-N (90)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11208540