Ok, I'll admit it. When I hear the phrase "the biology of aging" I'm mentally preparing myself to only understand about 5% of what the presenter is going to talk about (that's on a good day). While I have words like telomeres, sirtuins, or senolytics memorized for the boards, I've never been able to see how this applies to my clinical practice as it always feels so theoretical. Well, today that changed for me thanks to our podcast interview with John Newman, a "geroscientist" and geriatrician here at UCSF and at the Buck Institute for Research on Aging.
In this podcast, John breaks down what geroscience is and how it impacts how we think about many age-related conditions and diseases. For example, rather than thinking about multimorbidity as the random collection of multiple different clinical problems, we can see it as an expression of the fundamental mechanisms of aging. This means, that rather than treating individuals diseases, targeting aging pathways may be a better way to prevent or ameliorate multimorbidity. We talk with John about this, and current trials underway to test this hypothesis, along with so much more!
If you're interested in taking a deeper dive in the subject, take a look at these papers that John co-authored:
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Alex: This is Alex Smith.
Eric: Alex, we have someone in our studio audience ... our office studio? Our studio-
Alex: Our office studio? We have John Newman, who's a geriatrician and geroscientist-
Eric: A gero-what?
Alex: A geroscientist-
Eric: A gero-what?
Alex: A geroscientist who has held a joint appointment between UCSF and the Buck Institute for Aging Research. Welcome to the GeriPal PodCast, John.
John: Thanks, guys. Thanks, Alex. Thanks, Eric.
Eric: I'm really interested in figuring out what a geroscientist is. But before we do that, can we have a little song request for Alex?
John: Yeah, what should we sing about? Do you know a little song called Who Wants to Live Forever?
Alex: Ah, more Queen.
Eric: Boy, you can never get enough Queen.
Alex: Maybe our audience can. (singing).
Eric: John Newman does, right? John Newman wants all of us to live forever. At least that's why I am currently, those who are watching this on YouTube, can see I am getting fresh stem cells from my baby farm that I get infused every day, so I can live forever.
John: We're transfusing you as we speak.
Eric: As we speak.
John: As we speak.
Eric: Yeah, I give John hefty amounts of money for those baby transfusions.
John: Hey, that deal's just for you, Eric. Don't go advertising me.
Eric: So John, geroscience. What is this field, and is it about living forever?
John: It is not about living forever. It's about living healthier, longer, and staying independent. So what is geroscience?
Eric: That, I have no idea.
Alex: That's, I don't know.
John: I thought I was here, so you guys would tell me.
Alex: Gero ... Gero-
Eric: Gero- so, older.
Alex: Ger, Jerry, Ben and Jerry's.
John: Aging ... aging science.
Alex: Aging science.
John: Aging science with a flavor of people.
Eric: So what is the difference between you and Alex? You're both researchers. Is Alex a geroscientist?
John: Well, geroscience is a, it's a made-up word which was coined for a new field, and a whole new idea, which is now reality. Which is going to sound a little crazy. Taking what we know about the biological mechanisms that drive aging. The biology of aging.
John: And not only understanding that, which itself sounds a little crazy. But actually turning that into therapies, to help to treat or prevent disease, or help to improve the lives, especially of older adults.
John: Geroscience is the idea of translational geriatrics, taking what we know about the basic science of the processes that drive aging. And turning it into therapies and helping to improve people's lives.
Eric: The processes that ... Okay. As I age, I start developing some chronic medical conditions. They start building up. I have more and more medical conditions. If only I could just focus on making sure I don't develop those, or I treat these well; like diabetes, COPD. Would I prevent aging? Is that the goal here?
John: Well, one place this comes from is, what's that common underlying factor that's putting you at risk for COPD and for diabetes and for Alzheimer's disease and for cardiovascular disease and for strokes? And for osteoarthritis and osteoporosis? And for almost everything that we treat.
Eric: Nacho cheese Doritos?
John: That's a big one! That's a big one.
Eric: But there's more.
John: But what's the common variable for all of those? We call these age-related chronic conditions or age-related diseases.
Eric: Yeah.
John: Because they're all driven by aging. The key thing is that's not an accident or it's not just like a probability thing or it's not just time passing. But it's actually the biological mechanisms that change in our bodies as we get older that make us what we perceive as older. There's a biology there. And that biology puts you at risk for all these different chronic diseases.
John: You could try to treat or prevent all of these individually. But, if you're not changing, if you're not affecting the aging that's driving all of them, there's a limit to how far you can go with that, or how effective it's going to be.
John: You prevent diabetes, but you get cancer. You cure Alzheimer's disease, which would be amazing, but then you have a stroke. But if you intervene on the aging that's behind all of this, then maybe you can slow or delay or prevent all of these together. That's the great hope of geroscience.
Alex: Is delay or preventing aging ... Earlier, you said that it's not so much about living longer, as it is improving healthy years of life. And yet, but what you just said was, "delay or prevent aging." I'm a little lost there. Can you help me out?
John: Well, delay or prevent all of the diseases and conditions that are driven by aging. So, targeting aging as the underlying biology that causes or contributes to diabetes, dementia, cancer, heart disease, and all of that.
John: All of that might wind up helping you live longer; who knows. But that's not the goal.
Alex: Ah.
John: The goal is to be healthier for longer.
Alex: Oh.
John: To spend, so we all can spend more years independent and being able to do the things we want to do in a state of better health.
Alex: It's like the principle of the double effect. For those palliative care listeners, right, the primary ... right? We're relating the subject to you.
Alex: The primary intended target in the principle of double effect in palliative care is often opioids for pain relief. And yet, as a secondary effect, if the patient dies sooner, that's acceptable.
Alex: Your primary intended effect is to treat the disease that are associated with aging; the conditions that are associated with aging. As a secondary effect, if people end up living longer, then that's fine too. But it's not the primary target of geroscience?
John: I love that analogy. Living longer may wind up being a side effect of being healthier longer. But when you talk about ... Aging is a weird subject, right? Because it's this, it's not a disease. It's not a bad thing. There are many many positive elements of aging. I am happier now than I was 20 years. Hopefully I'll be even happier 20 years from now, even if I can't jump as high.
John: Aging is not a disease. It's not a bad thing. And yet we're trying to target, almost to treat it. The goal is if we can slow or reduce the bad aspects of aging, the parts of aging that give rise to chronic disease. And you're living healthier longer, you'll probably live longer, too, in good health.
John: When I go to a room and I ask people, "We're talking about aging as a target for therapies. Who wants to live to be 200?"
John: Not a whole lot of people raise their hands, because most of them are thinking, "I'm not sure how I'm going to feel when I'm 95 or 85 or 75. You extrapolate that out, and what am I going to feel like when I'm 200?"
Alex: Right.
John: That doesn't seem like a great choice. But if you ask people, "What if you could have the health that you have now, or the health that you had when you're 60, or the health you had when you're 50? And just keep that for longer?"
Alex: Uh-huh.
John: Most people would volunteer for that.
Alex: Interesting.
Eric: I just want to make sure that when you ... When I hear "aging," I think probably the common definition is, I'm getting older.
Eric: When you hear the word "aging," what do you mean by aging? Especially as we're targeting aging? I can't target the clock; I guess I could target my clock and just turn it around. What do you mean when you say "aging"?
John: Well, here's the geriatrician's perspective. How do we know what "old" is, what an older adult is, for making a clinical decision, for example?
Eric: Yeah.
John: For thinking about prognosis, for example. There's someone I know who's done a lot of work around prognosis and how to estimate someone's life expectancy.
Alex: I don't know who you're talking about [laughter].
John: Yeah, the name, it's right on the tip of my tongue. So how do we know? Of course, we know that someone's birthday doesn't really help a whole lot with that stuff. There's 85-year-olds who are very fit and active and healthy and young. And there are 85-year-olds who are not very young. What makes that difference?
John: In geriatrics, we think of things like functional assessments. Mobility and ADL function, idea function, frailty, trying to get that certain aspect of what does it mean to be older, to have an advanced stage of aging? Geroscience and aging biology is sort of the molecular reflection of that.
John: If we know that you have two 85-year-olds, and one of them needs help with ADLs, they're going to be at risk for complications from surgery. But not necessarily because they need help with ADLs, but because that reflects their biology. The stage of their aging.
Alex: Right.
John: We're learning more and more about what that biology really is.
Alex: Right.
John: Is it their telomeres, for example? Like Eric said earlier. Or how many senescent cells they have in their body. Or what is their NAD reserve? What is the state of their chronic inflammation? How are their proteins folding? What is their proteostatic resilience?
John: We're getting closer to be able to understand what all of these biological aspects are, so we can look at someone who we think, "Is this person an old 85-year-old or a young 85-year-old?" And know what their biology tells us.
Alex: I don't want to ... I mean, I don't want to belabor this point. But I know some of our listeners are probably skeptics. We have one skeptic, a nurse practitioner on our hospice and palliative care service. Patrice Villars. We mentioned we were doing this podcast.
Alex: And she said, "Is it," something along the lines of, "is it morally responsible to focus on helping people to live longer, given the current burden of climate change that humans are placing on the planet currently, much less if we were to live longer lives?"
John: I love that question. I love ... Aging is a really unusual field to study, because it's, again, it's not a disease. It's something universal that happens to all of us. That does make it a little bit different, and opens up these really interesting questions about not only how to study it, and what our goals should be; but also how to ...
John: If we have therapies that effectively target aging, target mechanisms of aging, who gets them? How do we decide how to use them? How do we decide who should have them and who doesn't get them? Is that different from the way that we decide who gets other treatments? These are really interesting questions.
Eric: In the work that you do, I'm guessing ... because I think this is a really fascinating thing to do, like if you extend the life, even 20 years, the ethical issues that come up. Even from a population density standpoint, can our earth even handle that? Then who gets all these treatments? In the field of geroscience, are there ethicists in that field, too, that are looking at these questions?
John: Yeah. This is a brand-new field, an emerging field. There are ethicists who are particularly thinking about these questions. Not very many, in the same way there's not very many clinician scientists who are helping to develop and study these therapies.
John: But there are people who are just starting to really think about, because these questions; even five years ago, this would have felt like a really academic philosophical kind of discussion. Therapies that target aging. Sure, let's maybe 10 years, 20 years down the line.
John: But the crazy thing is the first clinical trial that takes a drug in this case, that targets a cellular mechanism of aging, was given to older adults to treat a chronic syndrome of aging. That clinical trial, that first clinical trial has already been done.
Eric: What are they doing?
John: This was a drug that targets protein quality control. It's a drug called Rapamycin and its related drugs. We can talk about how this fits into the bigger scheme of mechanisms of aging. But it helps to activate pathways in your cells that clean up misfolded proteins and help your cells to make proteins that are more functional.
John: This drug and a related drug were first given to older adults before flu vaccine, to see if it would improve response to the flu vaccine. And it did. Then the next step, they did a clinical trial where they treated people with these drugs for just a month, and then gave them a flu vaccine, and saw that it improved their response to a flu vaccine.
John: But then over the next six months, they saw how often they got respiratory or other infections. What they actually found was that the people who received this treatment just for a month had about a third fewer infections over the next six months. So it had this really interesting long-lasting effect on their immune function in these older adults. It was helping to ameliorate what we call immunosenescence, the decline in function of our immune systems as we get older.
John: It's a really small, limited thing. One drug, some older people, flu vaccine, it was just looking at infections. Doesn't seem like a big deal, and it's not. Except it was the first randomized controlled trial of a drug like this that targets mechanisms of aging in older adults, to improve syndromes of older adults.
Alex: And it's already happened.
John: And it's already happened.
Eric: I guess that's probably the hard part with this is that I would imagine you can't do a randomized controlled trial with this drug for 20-year-olds and wait 90 years to see what happens to them. And then market that drug after a hundred years.
John: Exactly. I mean, hey, the average R01 lasts for five years.
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Geroscience and it's Impact on the Human Healthspan: A podcast with John Newman - GeriPal - A Geriatrics and Palliative Care Blog
