Exercise‐Induced Cardiac Lymphatic Remodeling Mitigates Inflammation in the Aging Heart
The lymphatic vasculature plays essential roles in fluid balance, immunity, and lipid transport. Chronic, low-grade inflammation in peripheral tissues develops when lymphatic structure or function is impaired, as observed during aging. While aging has been associated with a broad range of heart pathophysiology, its effect on cardiac lymphatic vasculature has not been characterized. Here, we analyzed cardiac lymphatics in aged 20-month-old mice versus young 2-month-old mice. Aged hearts showed reduced lymphatic vascular density, more dilated vessels, and increased inflammation and fibrosis in peri-lymphatic zones. As exercise has shown benefits in several different models of age-related heart disease, we further investigated the effects of aerobic training on cardiac lymphatics. Eight weeks of voluntary wheel running attenuated age-associated adverse remodeling of the cardiac lymphatics, including reversing their dilation, increasing lymph vessel density and branching, and reducing perilymphatic inflammation and fibrosis. Intravital lymphangiography demonstrated improved cardiac lymphatic flow after exercise training. Our findings illustrate that aging leads to cardiac lymphatic dysfunction, and that exercise can improve lymphatic health in aged animals.
Authors
- Aaron D. Aguirre (ORCID: https://orcid.org/0000-0002-5509-1646)
- Rebecca Freeman (ORCID: https://orcid.org/0000-0001-6493-5997)
- L. Zazzeron (ORCID: https://orcid.org/0000-0001-9169-1262)
- Justin Ralph Baldovino Guerra (ORCID: https://orcid.org/0000-0001-8507-5922)
- Charles Zhou (ORCID: https://orcid.org/0000-0001-9598-015X)
- Nicholas Houstis (ORCID: https://orcid.org/0000-0003-3812-2241)
- Kangsan Roh (ORCID: https://orcid.org/0000-0001-8067-7772)
- Ahlim Lee
- Sekeun Kim (ORCID: https://orcid.org/0000-0003-4196-6242)
- Siman Shen
- Anthony Rosenzweig (ORCID: https://orcid.org/0000-0001-6387-0386)
- Cedric Sheffield
- Fumito Ichinose (ORCID: https://orcid.org/0000-0003-4535-1632)
- Peng Xia (ORCID: https://orcid.org/0000-0003-3891-3385)
- Timothy P. Padera (ORCID: https://orcid.org/0000-0002-3453-9384)
- Rajeev Malhotra
- Jason D. Roh (ORCID: https://orcid.org/0000-0002-6999-6868)
- Yirong Zhou (ORCID: https://orcid.org/0000-0002-3470-4562)
- Haobo Li (ORCID: https://orcid.org/0000-0002-5660-7835)
- James Rhee (ORCID: https://orcid.org/0000-0002-2181-4957)
Institutions
- Tufts University (US)
- Scripps Research Institute (US)
- Harvard University (US)
- University of Michigan (US)
- Massachusetts General Hospital (US)
- Center for Systems Biology (US)
- Sungkyunkwan University (KR)
Publication Details
- Journal
- Aging Cell
- Published
- 2025-03-13
- DOI
- https://doi.org/10.1111/acel.70043
- Citations
- 9
- Primary Topic
- Lymphatic System and Diseases
- Type
- article
- Field-Weighted Citation Impact
- 9.41
Funders
- U.S. Department of Defense
- American Heart Association
- Foundation for Anesthesia Education and Research
- National Research Foundation of Korea
- National Institute on Aging
- National Heart, Lung, and Blood Institute