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Scientists Discover Cause Of Vascular Aging — And How To Reverse It — In Mice

A technician holds a laboratory mouse at the Jackson Laboratory in Bar Harbor, Maine. (Robert F. Bukaty/AP)
A technician holds a laboratory mouse at the Jackson Laboratory in Bar Harbor, Maine. (Robert F. Bukaty/AP)

A new study led by researchers at Harvard Medical School identifies key cellular mechanisms that cause blood vessels to age. Now, they’re looking for ways to apply what they found in mice studies to human health.

Here & Now‘s Jeremy Hobson talks with David Sinclair (@davidasinclair), the study’s senior investigator, a professor and co-director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School.

Interview Highlights

On what the research has found about what happens to blood vessels as they age

“Well as I’m sure many listeners know, as we get older we lose our vitality, we become weaker, we’re less able to exercise. We just don’t feel young anymore, and one of the main reasons for that is that we don’t have the blood vessels the blood flowing through our bodies as we used to. And as a result, what happens is that our tissues, our organs, they don’t get enough blood supply and they become deficient in oxygen. But also what happens is they can’t clear out the toxins. And this combination ends up leaving our tissues and organs susceptible to diseases from liver failure, kidney failure and even dementia. And what we are showing in this new study is that’s actually quite reversible, at least in mice, so far.”

On reversing that aging process

“We’ve been over at Harvard working on this for a number of years, 20 years. We first worked on the red-wine molecule resveratrol. Now we have new molecules that we think are even better. And it turns out it’s pretty simple how it works: We’ve figured out that there are genes in our bodies that respond to exercise and dieting, and we can turn those on with just some small molecules that seem to be safe so far in mice, and even so far safe in humans.

“When you give the molecule to the mice, what happens is their bodies — at least the blood vessels — they rejuvenate, they actually become no longer deaf to the signals from muscle. So they behave as though the mice have been exercising, and we have mice that in the lab are 2 years old, which is like 75-, 80-year-old human. And within a few weeks they become as fit and as vital as a young mouse again.”

On the potential for the study’s results to translate to humans

“I’m quite optimistic with this one, because our blood vessels work the same way as in mice. This isn’t a complicated disease like Alzheimer’s. And so I think that actually I’d be surprised if there isn’t some benefit in people. Of course the challenge is to make a drug, and we have to make sure it’s super safe, but we’re already doing human studies over the road from my lab at Harvard. And so far it looks really good.”

On whether the research would be applied to help treat disease, or get older people to exercise more

“This would be both. We’re working on having a drug available that your doctor could prescribe for you if you’re feeling frail or you have a disease such as muscle wasting, or even diabetes and even dementia, we think that this could be useful. But as a side effect, what we think the patients would notice would be improved stamina when they wake up in the morning, they don’t groan anymore. They can get back to exercising, and even people who have been in bed rest or in wheelchairs could potentially even get back to having mobility again.”

On remaining questions

“Mostly I wanna know how safe it is, and those are the studies that are ongoing right now. But hopefully by the end of this year or early next, we’ll actually know if the same effects are seen in human subjects, and it’s pretty easy to test if somebody gets increased endurance, you don’t have to wait years for the outcome. And then hopefully we’ll be able to see with further studies if this actually truly reverses aging throughout the body. This molecule that we’re giving the patients, or the test subjects, has the potential to actually extend lifespan in the same way it does mice. And so that’s really the holy grail here that we’re chasing.”

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