How biology and lifestyle affect our brains and bodies as we age

In this episode, Dr. Aditi Gurkar and Dr. Howard Aizenstein join us to discuss the biological indicators of aging, and the changes that can take place in cognitive function as we age. Listen to learn more about factors related to Alzheimer’s disease and dementia, along with practical steps each of us can take to support our cognitive health.

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Episode Transcript

Ellen

Stronger communities begin with good health—for everyone.

You’re listening to the “Good Health, Better World” podcast from UPMC Health Plan. This season, we’re exploring the joys, challenges, and opportunities associated with healthy aging. We’ll talk about what it means to age well; how to care for body, mind, and spirit as we get older; and the tools and programs available to ensure a good life, throughout life.

I’m your host, Dr. Ellen Beckjord. Let’s get started.

In this episode, Dr. Aditi Gurkar and Dr. Howard Aizenstein join us to discuss the biological indicators of aging, and in particular, the changes that can take place in cognitive function as we age. We'll discuss factors related to Alzheimer's disease and dementia, along with practical steps each of us can take to support our cognitive health.

Dr. Aditi Gurkar, welcome.

Aditi

Thank you. Thank you for having me.

Ellen

Dr. Howard Aizenstein, welcome to “Good Health, Better World.”

Howard

Thank you. Thanks for having me.

Ellen

We're thrilled that you're here. And I'll start with a general question, Howard, if I can direct it to you. At a high level—what happens to our brains as we age?

Howard

Well, the brain is like any other organ in the body and ages. It shrinks. Just like we see muscles atrophy, there's some atrophy in the brain. The psychology, the mind, our thinking also changes with aging. And there's some relationship between how the brain changes and how our thinking changes. But they're not complete. And there's lots of paradoxes. I mean, we see wisdom increasing with aging. And, we do see, patterns of normal—“normal” meaning we see them in people who are doing fine and having a healthy life—where there are, just like you see in the muscles in your body, some loss of tissue, a loss of volume. But there's other processes, as I mentioned, that add resilience.

Ellen
Would you mind talking with us about Alzheimer's disease and dementia—how they are related and different and the processes involved in diagnosing those conditions?

Howard

Dementia is the umbrella term. Alzheimer's disease is a specific type of dementia. There's a lot of debate about what exactly we mean by Alzheimer's and how wide a term we mean. Does it include most of what we mean by dementia? Or is it a more restrictive group, a more restrictive set? And I think people view it very differently. And the neuropathology tells a different story, too.

Regardless, we know there's cognitive and brain changes with aging that happen in people who are living productive and enjoyable lives well into their years. And they have these expected changes.

And we know there's a difference with dementia where we see a significant drop in functional ability and a significant change in the volume of different areas in the brain in neuropathology that can be seen under the microscope.

Ellen

For the umbrella of all kinds of dementia, is there a population prevalence that's generally agreed upon, like what percentage of people, and if it varies geographically, but what percentage of American adults go on to develop dementia as they get older?

Howard
It all depends on the age group you're looking at. And this is one of the really hard things to appreciate about Alzheimer's disease and dementia—it's not a linear relationship with age. It's more than linear. And so age is a very, very big factor. And it's not, as we'll talk more about here, it's not number of days since you've been born that matters. It's by aging we mean these cumulative changes that occur to many different organs and systems.

Ellen

Aditi your research looks at biological and chronological age. Tell us about those terms and a little bit about the focus of your program of research with respect to biological age.

Aditi
Sure. That's a great question, and I think something that we need to start considering today. Just like Howard mentioned, you know, chronological age is basically the number that's on your license or on your passport, right? Basically, how many times the earth has revolved around the sun. Sometimes I fudge the numbers, but, you know, we all know what the numbers are.

But when it comes to biological aging, that's a little bit more complex. And it is basically these cumulative changes that lead to functional changes both in memory and cognition, but also in function when we talk about walking ability and just doing our day-to-day functions. And so to figure out what’s one's biological age is quite challenging, as you might take. You know, depending on the day, I can remember where I parked my car most days, and then you put me in a different situation or into a new building, and I will not know where I have parked at all, right? And that does not always mean that you're aging. Sometimes it's the stress, sometimes it's the excitement. Like today we were excited to be here. And so, I might have forgotten where I've parked the car. Hopefully I'm not aging. <laugh>

And so biological aging is a little bit more complex to figure out. And so my lab is really looking at three fundamental questions. One, what is biological aging, in general? Can we find a molecular fingerprint for biological aging so that we can say, oh yes, you are chronologically 45, but biologically you look much more like a 29-year-old. That would be great. And that's kind of my hope. And the third question is, if we can figure out what one's biological age is, can we intervene early on? Can we tell, what's the risk factor for making this person age rapidly? And if so, can we find the right intervention with personalized medicine? So that's kind of the goal of what my research program is really looking into.

Ellen
That is so interesting. And you gave some, you know, informal examples of ways that context, sort of real time, hyperlocal context—How stressed am I today? What location am I in today?—that might affect one manifestation of your biological age, but are there known contextual factors that are less localized that may have to do with things that happen early in life, or just along the lifespan, that are known to likely influence biological age?

Aditi
Definitely things like not eating healthy or very stressful situations. We do know that that accelerates some of these, you know, functional loss[es] early in life. And that's, that's a very neat idea to hold on to because sometimes we think about aging and we think, oh, nothing—it's all beyond our control. And in many ways, it is, right? We probably cannot have the same function that we had as a 15-year-old. I wish we did.

Ellen

We cannot stop the earth from revolving around the sun.

Aditi

Exactly. But to have that hope that we could do things today that could lead us to have a better and healthier life tomorrow, I think that's very hopeful. And that's kind of the idea that I want people to take away when they think about aging and not just think about their chronological age and be like, oh, I'm in my 60s and I'm sort of done, you know. No, 60s can be the new 30s in many ways.

Ellen
I love that idea. And I'd like to ask, Howard, you a question, but before I do as I think about your complimentary respective areas of expertise, would it be fair to say that someone who develops dementia at a relatively early age, would that be an example, Aditi, of someone whose biological age has then far exceeded their chronological age?

Aditi
Right. And many factors can play into it. Sometimes that's genetics. We know that there are genetic polymorphisms that lead to loss of cognitive function early on. But sometimes it's not genetics and it could be anything else from lifestyle choices to environmental factors. So, I don't mean to say at all that everything is under our control, of course. But there are things that one cannot control. And, the other things maybe there are ways to figure out what we can do better.

Howard

There's a tiny bit of circularity that we all accept in the aging and Alzheimer's disease linkage with brain age that you just said. We do, we expect people with Alzheimer's disease, their brain age looks older than you'd expect it to. That's part of the diagnosis of Alzheimer's, though, that they have this atrophy and these brain changes. So, it gets a little bit circular.

If you look at early, rare familial Alzheimer's disease, like Presenilin-1 (PSEN1) disorders where they get amyloid production, and they get Alzheimer's at 40 years old, you won't see it. Their brain will maybe look a little older, but not as much. So, the model of thinking of Alzheimer's as just accelerated aging is partly true. And especially for late onset in the typical Alzheimer's.

Ellen

Dr. Aizenstein, would you please tell us about the Alzheimer's Disease Research Center here at the University of Pittsburgh, your role with it, and for listeners, we’ll make sure to include the website in our show notes.

Howard

Oh, thank you so much. I am so proud to be affiliated with the Pittsburgh ADRC, that’s the initials for the Alzheimer's Disease Research Center. It's a wonderful center, there’s a number of these throughout the country. National Institute of Health had this idea that to promote and move forward with Alzheimer's disease, there should be some organization of centers of excellence around the country. And Pittsburgh, I think, had one of the original ones, if not one of the ones very early on and it has made major contributions to Alzheimer's disease research and training investigators and clinicians, including myself and many, many of my colleagues. It's a model for a multidisciplinary research and clinical center.

People can contact them. They are a clearinghouse for lots of different clinical studies related to Alzheimer's disease. So they may have a study that's part of a national study network, or they may have a local study that they'll help get you in contact with.

My particular role, at this point (I've done different things over the years at the ADRC), is I get to lead the research education component with Jen Lingler and Melissa Knox, and that helps people get into Alzheimer's disease research, helps trainees at many different levels find their way. And it's been very rewarding.

One of the things it's been famous for recently is PET (positron emission tomography) imaging of amyloid. So, for many years, it was believed the only way to diagnose Alzheimer's disease was after someone died and to look in the brain and see the amyloid proteins under a microscope. Here in Pittsburgh, Bill Klunk and Chet Mathis, close colleagues of mine, of ours, developed a PET ligand, an imaging ligand. So you can see it in people when they're still living, and see the association of this important protein with cognition.

Ellen
Oh, wow.

Aditi

Yeah, that's a real fundamental discovery. It's amazing.

Ellen

If I could ask you to stay on the topic of research. What are some of, perhaps the most recent or the findings that you're the most excited about when it comes to either the prevention, the diagnosis, or the treatment of dementia or of Alzheimer's disease in particular?

Howard
I'm excited about all of the innovative, different approaches that are being tried. I'm not sure if there's going to be [a] simple solution. Though if there is, I think they're going to find it. It may be that it's more heterogeneous, more multifactorial, like aging itself, like cardiovascular disease. And it's going to involve a lot of prevention, taking better care of ourselves.

I'm very encouraged by the increased recognition of mental health and stress and sleep, and that these are, play a role and that people should pay attention to that. There's growing recognition of the term brain health relating to heart health. I like that, I think that's encouraging. I wish they would just as willingly say mental health as well as brain health, because that's just as important and often plays a big role. But I think people are less comfortable talking about internal challenges.

Ellen

We have talked at length about mental health on this podcast and while in some ways, the COVID-19 pandemic destigmatized some aspects of mental health, perhaps primarily mediated through the application of a global stressor. And sort of we all experienced the same stressor at the same time, not all in the same way, but there's definitely still a lot of work to do. I share your sentiment on that front.

Aditi, if I could ask you the same question in terms of what areas of research and discovery you're the most excited about when it comes to wellness and aging, including through the work that your lab does? And what are some concerns that you have as well?

Aditi

Sure. So to start with, I think what I'm most excited about is this concept of geroscience. What does that mean? I think people have looked at disease in a silo. So, people talk about, you know, Alzheimer's as our brain health and brain disease. But what we don't consider is all of these chronic challenges, illnesses, morbidities, they all come with age. Age is the primary risk factor for a number of these diseases. And it's been largely ignored.

I mean, Howard will tell you this, especially in the preclinical models where we've been looking for small molecules, therapeutics, drugs to solve dementia or Alzheimer's, one of the things that we do not take into practice is age. So all these preclinical models are genetic models who develop Alzheimer's when they're 6 months old. You know, that's very young. That's equivalent to a 25-year-old in a human.

Ellen

So if I understand you correctly, part of what you're saying is that as we look for these new pharmacological or perhaps even gene therapy interventions, not looking at them in the context of an aging organism or in organisms at various ages or even older ages if the animal models in the preclinical studies are looking at them at windows of time that would be the equivalent of young adulthood in a human model, that that's really missing an important contextual factor that should be considered.

Aditi

Exactly, exactly. And then the other idea to all of this is, none of our organs, none of our tissues age, you know, in independence, right, that there's this there's this communication—our brains talking to our muscle, our muscles talking to our heart, and so on, so forth.

So again, trying to put this all in a context has not been done as much before. So what I'm really excited about is this concept of geroscience, where instead of looking at one disease at a time, if you figure out how to age healthy, we'll probably be able to delay a number of these comorbidities for much later in life. And that could be the goal. So instead of solving just Alzheimer's or just cardiovascular disease or even cancer one at a time, maybe we can start thinking about, how can we delay aging?

Ellen

So this idea of taking a broader view around if aging is such a critical leverage point or factor in the epidemiology of so many different diseases, then it gets really interesting to think about rather than coming at one disease model at a time, if we could affect the aging process, might we have a broader impact?

But then as you were talking, I was sitting here thinking about how sedentary lifestyle, you know, sort of assault on systems with highly processed, ultra-processed foods, high levels of stress and distress. These things—I'm not trained in either of your disciplines, but I'm going to go out on a limb here and guess those are not super well aligned with delaying aging. And in fact, in many ways of thinking about it could even be seen as accelerators.

Aditi

Right, exactly. And I think that's where we as a society have started only thinking about disease. We are not thinking about health. You know, our major funders in science are the National Institutes of Health, right. But we are all again talking about disease, whether that's cancer, Alzheimer's. And as a modern society, we all sort of think, ”Oh, there's going to be a pill for everything.” We are all waiting for that magic pill. And so, we kind of think if we get heart disease, then we can do this. But if we can change that mindset and think more about how do we focus on health rather than thinking about what should we do once we have that disease? This would be the new outlook on medicine in itself, I think.

Ellen

I love all of that, and you've established your lab at the University of Pittsburgh relatively recently, is that right?

Aditi

Yes.

Ellen

Okay. And would you share just a little bit, maybe about some of the projects that you're working on and sort of where you're headed? I loved hearing about the big picture questions you're asking, but I'm so curious about your program of research.

Aditi

Sure. Yeah. We are very, very, very excited to be here at University of Pittsburgh. So, as I said, I do a lot of biology of aging. And being at Pitt, I think the most wonderful thing is I get to collaborate with geriatricians as well as other clinicians. And so, one of the most exciting projects has been trying to find a molecular fingerprint for biological aging. What does that mean? And what would that translate to? Let me give you a little bit of the big picture.

That would be when you go in for your annual checkups, doing a simple blood test could sort of predict if you're on the path of being a healthy ager or a rapid ager. With saying that I want to say like we are at the very early stages of this research. But what we've done so far is looked at a cohort of people about the age of 65, and we have looked at 200 people, and we sort of looked at them as healthy agers and rapid agers based on their functional ability.

That's walking, but also cognitive function by doing something called MoCA scores. And, at the end of this, we measured two things. We know aging is very complex. And that's why we think looking at just one factor, like just your cholesterol levels, is not going to give you a full picture.

So instead, we started looking at two different things. One is metabolites. So, metabolites are basically small chemicals that are floating through your body just through everyday processes. And they get affected by everything including genetics, what you eat, how much you exercise, have you gotten enough sleep, and why we decided to look at this, even though complex, is because all of these factors play into aging.

And then we combine that with another hallmark of aging called senescence. So, for the audience who doesn't know much about senescence, this is a cellular process where, as we age, we all start accumulating these dysfunctional cells in our bodies. In popular culture, they're known as zombie cells. And why they're called zombie cells is because they are resistant to dying.

So just like The Walking Dead, they just hang out in your body and start releasing a lot of inflammation factors. So, we decided to look at both these metabolites, along with how much zombie cells we have, [and] integrated this to find a molecular fingerprint for biological age. And what we see is 25 metabolites, out of, you know, 1,600 that are floating in us. So 25 of them could predict who's a healthy ager versus who's a rapid ager.

Again, this is very early on. What we would really love to do is how sensitive and how strong this predictor is. What that means is by doing healthy interventions, are we able to change that biological age? And second is how early on can we detect if someone's leading towards being a rapid ager?

Now, like I said, the cohort we looked at was all about the age of 65. But if we can start predicting this fairly early on in life, that's in our 40s, maybe then that's a real chance before these diseases set in to set off, change our mindset and think about, how can we age healthy and have much more of a quality of life, for our entire lifespan?

Ellen
Oh that's fascinating. That's so interesting. Thank you for sharing those details.

If we, I think, stay with the optimistic thread here. If I can start with you, Howard, and then ask you, Aditi, what are some things that people can do, some practical tips around preserving their cognitive function, their brain health, even their mental health if you care to comment, that folks can be thinking about, that they could start doing today?

Howard
Yeah. I think the term “listen to your better angels” is a good one. And I think it doesn't matter what your theological perspective is, we all have a sense of what's good for us, and we push against it, and we push against it in different ways. And eating well, you know, within reason, we know when it feels right. We know, we usually do. And it's finding ways to listen to those better angels and finding, being around people who help support them, finding structures to help support it.

I think it's often changing the question. Often people get frustrated that they're not doing things the way they expected to, but if they change what they want out of the situation, there's ways that there can still be a lot of meaning. And that's a big challenge throughout life—that flexibility.

Aditi

I mean, you know, I am a biology of aging, you know, always come with that perspective. And tons and tons of studies have shown that exercise and eating healthy are better than any magic pill that is available today. Of course, within reason, right? Just a simple walk, especially a walk with friends or family, right? So building social networks instead of being on your device, and going out for a walk, like it will change your perspective, even if it is a cloudy day outside. I think it makes you feel so much better. You just have a positive and more optimistic outlook to life. And, it's being shown in many preclinical models actually now that when you do even simple exercise and eat healthier, there's factors being released in the blood that even if you transfer that blood into an old animal, they do much better.

Ellen

Wow.

Aditi

Yeah. So this has some actual, you know, almost like a fountain of youth, right? We all have it in us in some ways. And so I am very optimistic as well for that reason that simple things like exercise, eating healthier, and building social, deep networks will change, our health, at many, many, many levels.

Ellen

I liked what you said earlier, Howard, about effectively listening to your body. I wonder if for lots of folks, especially in our very technology mediated existence these days, are we as embodied as maybe we ought to be? Are we in-tune enough with our physical experience of the world to know when—whether it's alcohol or what we're eating or how we are or aren't moving or are or aren't connecting—just paying attention, being mindful of what our bodies are telling us about whether things feel good or bad or not enough or too much? I think that's very good practical guidance, because oftentimes I think that messaging is coming through if we just kind of tune in to it.

Howard

I think that's right. I think we're we are, through social media, really being pushed to want certain things. And I think it is, that's why disconnecting and listening to yourself is always good advice.

Aditi
Yeah. I mean, you know, that brings into play why there are so many TV ads for food at 12 midnight, right? Because when you're watching these, you're automatically wanting to go eat a big burger. And the same is happening with social media because we all watch, you know, shorts and videos all the time. And they're showing about this fantastic croissant that’s, you know, in Paris. And I'm watching this at 11 in the night, my tummy is like, I really need this. And my brain is like, I really need this. <laugh> And so sometimes we give in to it, right? And that's happening more and more because we are all reliant on our devices, you know, less sleep, and watching these kinds of things, late at night. And instead of actually doing the good practices and listening to our bodies and resting, now we want that croissant. <laugh>

Ellen

Well, Aditi, Howard, I want to thank you so much for taking time to talk with us on “Good Health, Better World.” I was so interested in what you had to say. And I'm really grateful that you're both here in Pittsburgh doing the work that you're doing. I think it's good news for all of us. Thank you for being here today.

Howard

Thank you. Thanks for having me.

Aditi

Yeah. Thank you for having us. It's been a blast and I've learned so much. So thank you.

Ellen

We hope you enjoyed this episode of “Good Health, Better World.” Be sure to tune in next time and visit upmchealthplan.com/goodhealth for resources and show notes.

This podcast is for informational and educational purposes. It is not medical care or advice. Individuals in need of medical care should consult their care provider. Views and opinions expressed by the host and guests are solely their own and do not necessarily reflect those of UPMC Health Plan and its employees.

Guest Speakers:

Dr. Aditi Gurkar

Assistant Professor of Medicine, Aging Institute and Division of Geriatric Medicine, University of Pittsburgh

Dr. Gurkar received her PhD degree from Boston University School of Medicine. She completed postdoctoral work at Massachusetts General Hospital/ Harvard Medical School & Broad Institute and then at Scripps Research Institute, Florida. She joined the faculty at the University of Pittsburgh as an Assistant Professor in the Aging Institute and the Division of Geriatric Medicine. Her lab focuses on defining the metabolic and senescence signatures of human aging. She is funded by the NIH, AFAR/Hevolution, National Academy of Medicine Longevity grant and RK Mellon Foundation. Outside of the lab, Dr. Gurkar is involved in multiple community outreach programs to engage people in “healthy aging” initiatives.

Dr. Howard Aizenstein

Professor of Psychiatry and Bioengineering, University of Pittsburgh

Dr. Aizenstein is an expert on the cognitive and affective neuroscience of aging and geriatric brain disorders. He is trained as a geriatric psychiatrist and also a computer scientist. His research program is recognized for expertise in MRI analyses methods, as well as their use for clinical research in aging. Dr. Aizenstein’s research group has developed semi-automated methods of morphometric and functional MRI analyses. He uses structural and functional neuroimaging to identify networks of brain regions associated with affective and cognitive processing, and how these change over time with and without intervention.