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Professor Mara Mather: Slowing down the progression of Alzheimer’s disease

By Alzheimer's and Dementia, Lifespan Health, Podcast, Research

Mara Mather, Professor of Gerontology and Psychology at the USC Leonard Davis School of Gerontology, is shedding light on how we learn, what we remember, and where we might find clues to slowing the progression of Alzheimer’s disease.

Quotes from this episode

“What is it that you remember? The things that you remember are typically the things that were really emotional in your life that mattered to you, that were surprising, that stood out. And we also can notice ourselves how much we tend to have gaps in some of these memories. And so scientists have been interested in this for a very long time.”

“We looked at a sample of several hundred adults and we found among the older adults that the integrity of the locus coeruleus or this brightness that it shows on our MRI images because of its magnetic properties – as that declines with age, it seems that the locus coeruleus is probably showing some neuronal loss. And we found that that signal was associated with how well people did on memory tests. So people who showed what looked like a more intact locus coeruleus were doing better on memory tests.”

“It turns out the locus coeruleus is a really fascinating area to look at in aging because it is the first place that Alzheimer’s pathology is seen. And what I mean there is when you hear about Alzheimer’s disease, you hear about plaques and tangles and the plaques are amyloid beta pathology and the tangles are related to tau pathology and tau pathology starts in the brain quite a bit earlier than the amyloid.”

“I think that Alzheimer’s is more like cardiovascular disease. It’s a spectrum and we’re all somewhere on this spectrum. We all have a little bit of the disease pathology the way that we probably all have some atherosclerosis lurking somewhere in our cardiovascular system. What this means is that, Alzheimer’s is this very slow-moving process and what we really want to be doing is slowing it down.”

“That high arousal state is helping you to learn new things and shape your brain and keep your brain plastic as you get older or throughout life. But those high energy, high metabolic brain plasticity processes are creating waste, they’re producing things like amyloid and tau. So you’ve got these positive aspects that leads to brain plasticity, but it also can lead to more pathology.”

“You need both the high arousal, sympathetic nervous system, properties that allow for brain plasticity. And you also need these relaxation, parasympathetic properties that allow for things to be repaired and for waste to be cleared out. And you need to go through both of those states every day pretty much to maintain a healthy balance of both really high performance and dealing with the consequences of having had all that brain activity.”

“And so my hope and my ambition is to try to figure out the balance where you can engage the brain in intense mental stimulation that leads to growth and neuroplasticity. And we can also figure out optimal ways to either restore deep sleep and enhance that or do these sort of meditative or heart rate variability, biofeedback sort of practices that can mimic some of the aspects of deep sleep and allow for the clearance of the waste products of that really high mental stimulation.”

“One study that looked at a large sample of people who have practiced meditation for many years versus people who have not practiced meditation found that when they just used a machine learning technique to guess at how old the brains were of each person. This algorithm guessed that on average, the meditators brains were 7.5 years younger than their actual age and compared to the control brains, which were non-meditators and didn’t show that effect. So it seems that meditation is associated with benefits for the actual brain health, which is really interesting, whether this might be because over years, they’ve had better clearance of these potentially pathological aspects that when they accumulate for many years eventually lead to Alzheimer’s disease.”

Learn more about Professor Mara Mather and her work at https://gero.usc.edu/faculty/mather/

Headshot of Bérénice Benayoun with name and faculty title

Professor Bérénice Benayoun: Advancing new models for aging research

By Lifespan Health, Podcast, Research

Bérénice Benayoun, Assistant Professor of Gerontology at the USC Leonard Davis School of Gerontology, is advancing what we know about how cells age, and how they can possibly be returned to a more youthful state, by focusing on areas that have historically been overlooked.

Quotes from this episode

The reason it’s so powerful is because we can recapitulate most of what you expect from aging in that short amount of time, including cognitive decline, increased amount of cancers, decreased fertility and all of that.

And, it’s not that they’re dying of like something random. They are dying of aging. When we look at all the signs, they have all the signs of aging, which means we can recapitulate an entire human lifespan in less than six months. And so, that’s very attractive to study aging — diseases of aging — as a model.

One of the problems is they can integrate themselves in genes that are important for cell health, including tumor suppressor genes. And so, when they go everywhere, they’re going to create that increasing mutational load, and they can actually drive tumor genesis, right, by turning off the safeguards against uncontrolled cell proliferation. That’s one thing. The other thing is, they look exactly like viruses as far as our immune system is concerned. They used to be viruses. And so, when our immune system sees a transposon being expressed, it actually activates and tries to kill it.

Maybe, part of the problem with aging is we have sort of an autoimmune response against those viruses, and we know that sustained immune response — which is, you know, this inflammatory response — is actually very bad for us.

At least in immune cell types, aging creates many more changes in female cells than in male cells. That could explain a lot of the differences in immune diseases. Young women are much more subject to autoimmune diseases, like lupus. It’s a frequency of nine to one for women to men, but that decreases after menopause, right? So again, there’s a huge interplay between hormones and immunity and immune cell types. We see that aging creates many more changes in females than in males.

Most people actually just study males, and we know very little about differential mechanisms, and not just with aging, it’s across fields. All of these people usually just study males, whether human or mouse because it’s simpler.

We’re studying aspects of immunity, and we’re actually saying that the immune response is vastly different depending on where those mice are in their hormonal cycle. And so, you know, yes, the data, it looks noisy, but if you’re actually stratifying it by the hormonal status, it’s not more noisy, and it gives you more information.

Learn more about Professor Bérénice Benayoun and her work at https://gero.usc.edu/faculty/berenice-benayoun-phd

Headshot of Dana Goldman with name and titles

Professor Dana Goldman: Investing in health

By Lifespan Health, Podcast

Dana Goldman, USC Distinguished Professor in public policy, pharmacy, and economics and director of the Schaeffer Center for Health Policy & Economics at the USC Price School of Public Policy, is working to improve health – and reduce spending – by calling for policy changes that reward prevention, innovation and long-term investments in people of all ages.

Quotes from this episode

“I’m a little concerned that in the current debate, we tend to focus mainly on costs and insurance. And the questions around aging are much broader and more dynamic than the current policy debate gives it attention.”

“There’s a very good drug, for example, that’s under development … it reduces cancer, reduces cardiovascular disease, may be protective for all Alzheimer’s, helps with diabetes. And that drug is called exercise. And we’ve done a lot of research on it, and we know it’s very good, but there’s no incentive for anyone in our healthcare system to take older people for a walk. And yet, we know that would be extremely valuable.”

“If I develop a pill, I have a patent system that gives me some protection. And if I take the risk to figure out some way to get this to patients, I know that someone can’t copy it until my patent has expired. And that has encouraged the development of a lot of pills. But if I come up with a way to get you to walk or eat better or something like that, it’s very easy for someone to copy that. And so you can see that the playing field is tilted more towards treatment and less away from prevention just because of the way we think about intellectual property.”

“Historically, the way we’ve paid for health care is we paid dollars for volume of services. So you have an office visit, you get paid. And the system has responded by giving us lots of volume of healthcare services. But that’s not actually what people want. I mean, they aren’t looking to go to the doctor every week. What we really want as a society is good health.”

“We need to pay for health, not health care. And if we do that, then we’ll be able to accumulate some savings out of the system that I think would help pay for all the other types of infrastructure investments that would make sure that people lead wholesome, long, productive lives.”

Learn more about Professor Goldman and his work at https://priceschool.usc.edu/people/dana-goldman/.

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