Targeting Aging to Prevent Disease and Extend Healthspan

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• Lifespan vs Healthspan
• Aging as a Disease
• Disease Impact on Aging
• Targeting Fundamental Aging Processes
• Regulatory Challenges
• Full Transcript

Lifespan vs Healthspan

Dr. Steven Austad, MD, clarifies that lifespan and healthspan are not the same. Human lifespan has been increasing rapidly for almost 200 years. Healthspan has been growing less rapidly. The period of unhealthy life at the end is now longer than it was decades ago. Dr. Steven Austad, MD, emphasizes the need to understand what determines healthspan.

Aging as a Disease

Dr. Steven Austad, MD, discusses the movement to reclassify aging as a disease. He notes this may make sense from a marketing perspective to gain more attention. However, aging itself is not a disease. It profoundly influences the development of diseases. This distinction is crucial for how we approach medical research and treatment.

Disease Impact on Aging

Dr. Steven Austad, MD, explains the bidirectional relationship between disease and aging. Diseases can also accelerate the aging process. He cites the example of people living with well-controlled HIV who age at an accelerated rate. This may be due to chronic low-level inflammation or a response to long-term antiviral drugs. Cancer chemotherapy is another example. It treats cancer effectively but causes significant bystander damage that can accelerate aging.

Targeting Fundamental Aging Processes

Dr. Steven Austad, MD, proposes a paradigm shift in medical research. He suggests targeting the fundamental processes of aging. This approach could delay or prevent all major age-related diseases as a group. He uses the analogy of a cancer prevention drug that also prevents dementia, heart disease, and osteoarthritis. This represents a completely different way of thinking about biomedical intervention. It moves away from the atomized study of individual diseases.

Regulatory Challenges

Dr. Steven Austad, MD, highlights a significant barrier to this new approach: regulatory agencies. The FDA only approves drugs for specific diseases. Dr. Austad recounts a meeting with the FDA about five years ago. They discussed trials for drugs targeting aging. The conversation had to be framed as a single drug targeting multiple diseases. The FDA does not recognize conditions like sarcopenia (age-related muscle loss) as a disease. This prevents the approval of drugs to treat it. Dr. Austad concludes that this is more than a semantic issue. It fundamentally affects how we conduct science and develop treatments.

Full Transcript

Dr. Anton Titov, MD: So that brings us to the very important part of the concept of lifespan and healthspan. And lifespan and healthspan are not necessarily correlated. So how does the disease process influence the aging process?

Dr. Steven Austad, MD: You're right. They're not the same thing. Lifespan and healthspan are not the same things. Lifespan in humans has been increasing very rapidly, six hours a day, for almost 200 years now. Healthspan has been growing less rapidly. And in fact, the length of unhealthy life at the very end is a little bit longer than it was even 20 or 30 years ago.

So what we need to do is understand what determines healthspan. And we must think about it differently than we think about diseases. There's been a move in the field now to sort of reclassify aging as a disease. And I think while that may make sense in a marketing sense—that is, it may get more attention if we treat aging as if it were a disease—it is not a disease, but it influences diseases.

And then diseases, paradoxically, can also influence aging. One of the more interesting things we've learned recently is from people that are living with HIV that is very, very well controlled. And so there's very little virus in the blood. But they have been aging at an accelerated rate.

Does that have to do with some sort of low-level inflammation? We know that low-level chronic inflammation increases with age. It may have to do with some sort of response to the antiviral drugs that these people are taking chronically. We don't know. But it emphasizes the impact of diseases on aging, as well as aging on the disease.

We know that, for instance, cancer chemotherapy can accelerate aging. Chemotherapy can be great for treating cancer, but it does all kinds of bystander damage, as they call it.

Dr. Anton Titov, MD: You bring up the issue of aging influencing the disease, but also disease influencing aging. Considering hundreds of billions of dollars that are spent on diseases, and especially fighting it at the very late stages, would it not make sense to direct more research to the fundamental process of aging and to see if you can influence cancer and dementia at a fundamental level?

Dr. Steven Austad, MD: Yeah, that's a very good point. And it's a point that we try to get across, which is that aging underlies all the major diseases, all the major causes of death. And if we can target and modify the underlying processes, then we have the possibility of delaying or preventing all of these diseases as a group.

Think of it this way: I developed a cancer prevention drug, but it has several side effects. One of the side effects is it prevents dementia, and another side effect is it prevents heart disease and osteoarthritis and a whole bunch of other things. That's what we're talking about.

It's a completely different kind of thinking about biomedical intervention than what we've done before. If you think about it, the whole medical field is atomized into studying different diseases. We have our oncologists, our neurologists. But what's happened is this: as they started talking to one another in recent times, they realized that the same process is underlying cancer and heart disease and neurodegenerative diseases.

So maybe we have been doing this wrong. Maybe we want to target fundamental aging processes. One of the things that have prevented this is the Food and Drug Administration because they will only approve drugs for specific diseases.

And so a number of us had a meeting with the Food and Drug Administration about five years ago, trying to get their opinion on whether we could do a trial with a drug that targeted aging. But we couldn't say it in those terms. We had to say it in terms of a single drug that targeted multiple diseases.

And once we put it like that, FDA said, okay, yeah, in principle, we could approve a drug for that. And so we're hoping that the FDA changes its view on this. FDA doesn't, for instance, consider sarcopenia, an age-related muscle loss, a disease either. That means they can't approve drugs to treat sarcopenia.

So there's this. This is more than a semantic issue. This is an issue that addresses how we do science, unfortunately.