How to Keep Blood Vessels Young and Fight Aging

Aging

How to Keep Blood Vessels Young and Fight Aging

• January 10, 2025

The body's vasculature - its arteries, veins and capillaries - keeps our physiology running smoothly. It's the conduit for delivering oxygen and nutrients, collecting and removing waste and toxins, and dispatching the immune system's agents when and where they are needed.

Together, these roles ensure the health and function of all our tissues and organs. And because the vascular system pervades all our bodily operations, Anastasia Paulmann, M.D., sees preserving its integrity as the key to warding off a host of diseases associated with aging.

"You definitely don't want your least-healthy organ system to be your vasculature, because it serves all of your other organs," says Paulmann, a post-doctoral researcher in the research group of MDI Bio Lab President Hermann Haller, M.D.

Paulmann is working to identify new interventions for vascular function that will prolong our lives and keep us healthier. She began her career as a clinical doctor, helping people recover from kidney transplant surgery, and her heart remains with the patients, she says.

Her physician's perspective embodies MDI Bio Lab's commitment to both basic biomedical research and to revealing the mechanisms that will make real-world differences in human lives.

"In the end, it's whether you can take a finding like this from the lab to the clinic," Paulmann says. "How can we make it as easy and accessible for as many people as possible?"

As people age, the vascular system's condition often degrades: larger blood vessels become stiff, limiting their flexibility and capacity; smaller vessels become less dense, reducing the number of routes the blood can take to deliver its vital services. The process is called "rarefaction."

Images of young and old kidneys of the African turquoise killifish, marking blood vessels in bright green (Microscopy by Anastasia Paulmann, M.D.)

Vascular rarefaction can drive the development and progression of a wide variety of disorders, such as hypertension and heart disease, kidney disease, cognitive decline and Alzheimer's disease.

"If we can keep the vascular network dense, as when it is young, the organs will function as if they're young," Paulmann says. "You can not only prolong lifespan, but you can keep age-related diseases away."

She is studying the molecular mechanics of how and why rarefaction occurs, and whether some existing pharmaceuticals could slow or even reverse it.

Paulmann says aging's effects on the blood vessel system appear to be most acute within the microvasculature - the tiny capillary vessels that mark the point where oxygen, nutrients and waste are exchanged between blood, tissue and organs.

"When we are young, we have a very dense capillary network, and when we age, we keep losing more and more of these capillaries," she says. "I'm trying to measure when exactly this happens in the killifish. Can I see it? And then, of course, the big question is: 'What is happening? Can we reverse it? Can we stop it?' "

Paulmann thinks we can.

But rather than launching expensive and time-consuming experiments with typical models such as mice, Paulmann is doing cutting-edge work to establish the African turquoise killifish as a powerful new tool for biomedical research on aging.

Called ATK for short, the fish has one of the shortest lifespans of any vertebrate, typically living only about three to six months. That allows Paulmann to study the full life cycle and aging process within a relatively brief timeframe, speeding the acquisition of experimental data and making it more cost-efficient.

She's found that in both ATK and humans, a loss of capillary density is associated with a change in how the body processes and uses energy, with more metabolic dependence on sugars such as glucose, rather than on fats or proteins.

That's fired her interest in a class of molecules that are known to affect the way we reabsorb glucose in the kidney. Called "sodium-glucose linked transport inhibitors" (SGLT2is), they have proven to be a useful therapy for treating diabetes, kidney, heart, and fatty liver disease, while showing few side effects.

And in her experiments with African turquoise killifish, Paulmann is now documenting the drug's positive effects on vascular health as well. Playing to the Haller group's expertise in kidney functionality, she's focused on renal vasculature.

"We were able to show that in fish that we've treated with this intervention, longer life can be achieved, " she says. "And we saw that just at the time when age normally begins to significantly degrade kidney vasculature, the treated animals are showing more robust vasculature and lower levels of rarefaction."

"Our hypothesis is that this process is important for the aging process and what the implications are for organ function such as kidney, hear and brain" she adds. "It's very exciting. It's a big field now, and everyone is trying to find out the one mechanism that makes this drug work."

Note: Pullman and Haller will explain their research and take your questions in an online MDI Science Cafe February 3rd at 5 pm. Details at left!

Images of young and old heart of the African turquoise killifish, marking blood vessels in bright green (Microscopy by Anastasia Paulmann, M.D.)

• African Turquoise Killifish
• Anastasia Paulmann
• SGLT2is
• vascular