News · Longevity & Aging
Aging hearts lose their drainage vessels, and in mice that loss helped drive inflammation
The heart has its own network of lymphatic vessels that help keep fluid in balance. In old mice, and in a small set of human heart samples, that network thinned, and restoring it in mice calmed inflammation.
- This work was done mainly in mice, with supporting data from the heart tissue of five older people.
- Old mice had far fewer lymphatic vessels in the heart, with tighter junctions between their cells.
- Fewer vessels went with more immune cells, fluid build-up and stiffer heart filling.
- Removing lymphatic vessels in young mice reproduced key features of the aging heart.
- Restoring the vessels in old mice reduced inflammation; no treatment was tested in people.
Ask someone to name the heart’s plumbing and they will usually mention arteries and veins. There is a third network that gets far less attention: lymphatic vessels, which help drain excess fluid from tissues and carry white blood cells. A new study, done mainly in mice with supporting data from five people’s heart tissue, suggests this drainage system in the heart thins out with age, and that the loss helps fuel inflammation.
When researchers stripped lymphatic vessels from young mouse hearts, those hearts started to look old. When they helped the vessels regrow in old mice, inflammation eased.
What do lymphatic vessels do in the heart?
MedlinePlus describes the lymphatic system as a network of tissues and organs that includes lymph vessels, which carry a fluid containing white blood cells and are separate from blood vessels. It explains that the system clears away infection and keeps your body fluids in balance, and that when it is not working properly, fluid builds up in tissues.
The heart has its own lymphatic network. The authors note that aging drives structural and functional decline in the heart, raising the risk of a form of heart failure in which the heart struggles to relax and fill. The role of blood vessels in that process has been well studied, but the role of the cardiac lymphatic vasculature in this process remains poorly understood.
What happened to lymphatic vessels in old hearts?
Writing in Nature Cardiovascular Research, the team compared mice aged 18 to 20 months, elderly for a mouse, with 3-month-old young mice. Old mouse hearts had substantially fewer lymphatic vessels, in both males and females. Reanalyzing existing data on heart tissue from five people in their 60s, the researchers saw a similar reduction with age.
The vessels that remained had changed shape. The junctions between the cells lining them became tighter and zipper-like. Alongside that, old hearts showed more immune cells moving in, build-up of proteins called fibrinogen and amyloid, and swelling from fluid in the heart muscle. Heart scans showed the old mice had trouble with how the heart relaxed and filled, while its pumping strength stayed normal.
Did losing lymphatic vessels cause the aging changes?
To test cause and effect, the researchers reduced lymphatic vessels in the hearts of young mice, using two different genetic methods. Both times, the young hearts developed key features of cardiac aging: inflammation, damaged lymphatic vessels, and problems with how the heart filled.
That is the core of the study. The loss of lymphatics does not just accompany the aging heart in mice. Taking the vessels away was enough to push young hearts in the same direction.
Why do the heart’s lymphatic vessels decline with age?
The team traced part of the answer to a signaling protein called interleukin-33, or IL-33. With age, lymphatic cells made more IL-33 inside their nucleus, and that form of the protein promoted cell death and the tightening of junctions. An inflammatory signal called interferon gamma, which was higher in old hearts, raised IL-33 in lab-grown lymphatic cells.
On the other side is VEGFC, a growth factor that supports lymphatic vessels. Its levels declined with aging, and it normally keeps IL-33 in check.
Could lymphatic vessels in the aging heart be restored?
In old mice, the researchers used a modified virus to deliver extra VEGFC to the heart, or to switch off IL-33. Both approaches restored lymphatic density and reduced immune cells in the heart. The authors say VEGFC could partially restore the vessels and attenuate what they call cardiac inflammaging, the low-grade inflammation that builds up with age.
What can’t this mouse study of heart aging show?
The human evidence is small, drawn from five people’s heart tissue in an existing dataset. Most of the findings, including every experiment that tested cause and effect, come from mice.
The authors are careful on the key question for patients. They write that whether restoring lymphatic density can prevent or reverse age-related heart disease remains an important unanswered question, and that the long-term side effects of any such treatment would need careful evaluation.
What does lymphatic aging mean for heart health?
For now, it is a new way of thinking about why hearts stiffen and inflame with age, not a new treatment. The authors do point to earlier studies suggesting that growth of new lymphatic vessels may contribute to the heart benefits of exercise, although this study did not look at exercise.
If the findings hold up in people, the heart’s overlooked drainage system could become a target for keeping aging hearts healthier. That is a long road, but it starts with noticing that the plumbing matters too.
People also ask
What did the study find?
Aging reduced cardiac lymphatic vessel density in humans and mice and caused tighter, zipper-like junctions between vessel cells, along with immune cell infiltration, fibrinogen and amyloid build-up and fluid in the heart muscle. Reducing lymphatics in young mice reproduced inflammation and impaired lymphatic integrity. Aging increased nuclear interleukin-33 in lymphatic cells, and boosting VEGFC or silencing IL-33 restored lymphatic density in aged hearts.
What are lymphatic vessels?
Thin vessels, separate from blood vessels, that carry lymph, a fluid containing white blood cells. They help clear away infection and keep body fluids in balance.
What is inflammaging?
The persistent, low-grade inflammation that tends to build up in tissues with age.
What is diastolic dysfunction?
A problem with how the heart relaxes and fills between beats. The old mice in this study showed it while their pumping strength stayed normal.
Can exercise protect the heart's lymphatic vessels?
The authors mention earlier studies suggesting that growth of new lymphatic vessels may contribute to the heart benefits of exercise, but this study did not test exercise.
Is there a treatment based on this?
No. The authors say it is still unanswered whether restoring lymphatic vessels can prevent or reverse age-related heart disease, and that any long-term side effects would need careful study. This is general information rather than medical advice.