Understanding the Evolution of Aging and Strategies for Healthy Longevity

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• Evolutionary Theories of Aging
• Selective Pressure Decline and Disease Onset
• Antagonistic Pleiotropy Theory
• The Aging Intervention Paradox
• Extending Healthspan and Lifespan
• Future of Aging Research
• Full Transcript

Evolutionary Theories of Aging

Dr. Brian Kennedy, MD, discusses the most supported theories of aging with Dr. Anton Titov, MD. Evolutionary studies provide the most informative perspective on why we age. A key concept is the breakdown in natural selection. This occurs as an individual's role in fitness declines with advancing age.

Dr. Brian Kennedy, MD, explains that once people pass a certain age, they are typically no longer having or raising children. This historical reality has profound implications for the forces that shape our biology.

Selective Pressure Decline and Disease Onset

The decline in selective pressure is a critical factor in the aging process. Dr. Brian Kennedy, MD, notes that historically there has been less pressure to keep older individuals healthy. This lack of evolutionary pressure allows biological systems to gradually break down.

Dr. Kennedy points to a specific timeline for this phenomenon. The selective pressure declines significantly after the age of about 40. This correlates directly with the onset of visible age-related changes. It also marks the beginning of chronic conditions that arise from these biological changes.

Antagonistic Pleiotropy Theory

Dr. Brian Kennedy, MD, explores the concept of antagonistic pleiotropy with Dr. Anton Titov, MD. This theory proposes that certain genetic mutations can be beneficial in early life. These same mutations, however, carry a cost that manifests later in life. The benefit of survival and reproduction in youth outweighs the detrimental effects in old age.

This creates an evolutionary trade-off. Dr. Kennedy also mentions other perspectives. Some researchers view aging as a programmed process to remove older populations. It may also be a consequence of other evolutionary pressures.

The Aging Intervention Paradox

A fascinating paradox exists in aging research, as described by Dr. Brian Kennedy, MD. He entered the field around 1990 with a common assumption. Experts believed understanding aging would be easier than intervening in it. The reality has proven to be the opposite.

Dr. Brian Kennedy, MD, states that understanding aging is profoundly complex. However, intervening to delay its effects is surprisingly achievable. He uses a powerful analogy. Improving a semi-dysfunctional system, like an old car, is easier than optimizing a perfect one. Aging represents that semi-dysfunctional biological state, making it a tractable target for improvement.

Extending Healthspan and Lifespan

Numerous interventions now successfully delay aging in model organisms. Dr. Brian Kennedy, MD, highlights this exciting progress. These interventions do more than just extend the quantity of life, or lifespan. They crucially extend the quality of life, known as healthspan.

This means they prevent or delay the onset of age-related diseases. A single genetic mutation or one drug can often produce significant effects. This is precisely because aging is not under strong selective pressure for optimization. The goal is to apply these findings to promote healthy longevity in humans.

Future of Aging Research

The current focus of the field is shifting thanks to these discoveries. Dr. Brian Kennedy, MD, explains the new challenge. Researchers are now trying to figure out why these interventions work so effectively. The ease of delaying aging points to fundamental biological pathways that can be modulated.

Dr. Anton Titov, MD, facilitates this discussion on the future direction of geroscience. The conversation underscores a message of hope. The biological processes of aging, while complex, are not immutable. They can be targeted for therapeutic benefit to improve human health in later life.

Full Transcript

Dr. Anton Titov, MD: Is aging an adaptive trait? There are several theories of aging. What theory of aging has the most support today?

Dr. Brian Kennedy, MD: I think the studies on evolution were probably the most informative. You have a breakdown in natural selection with a declining role of fitness. When people reach a certain age, they're not having children or raising children anymore. There historically has been less selective pressure to keep those people healthy.

Then the question is whether things just begin to break down in the absence of that selective pressure, or if something like antagonistic pleiotropy is going on. You have mutations that keep you healthier when you are younger, and the cost is things going wrong later in life.

There are also people that see aging as a program that may be in place for some reason to get rid of the older population or as a consequence of some other pressure. So I think we're still debating those kinds of things.

It's pretty clear, however, that the selective pressure declines after the age of about 40. And that's about the time you see the onset of age-related changes and chronic conditions that arise from them.

Dr. Anton Titov, MD: In one of your publications, you also mentioned in several reviews that despite the natural aging process, it seems like there are several programs that can be easily activated by changing one or a couple of groups of genes. Therefore, aging is not necessarily absolutely programmed in evolution.

Dr. Brian Kennedy, MD: Yeah, I think the striking thing when I started in the field in around 1990 is that most of the aging field would have said, by 2020, we'll know a lot about aging, but it'll be really hard to do anything about it in humans because it's such a complex phenomenon. What we've learned is that it's really hard to understand aging, but it's really easy to do something about it.

So there are lots of different interventions now that extend lifespan in a whole range of model organisms. They extend healthspan, they prevent age-related disease onset. And now we're trying to figure out why that is.

One way to think of it is that if you have something that's already fully optimized, it's really hard to improve upon that, especially by mutating one gene or giving one drug. But aging is not under that selective pressure. Aging is sort of what goes wrong after pressure declines.

And so it's easier to make things better, because you're starting from this semi-dysfunctional system and trying to improve it. If you want to make a car work better, you don't start with a fully functional Mercedes where there's nothing wrong with it. You start with a used car you get almost in the junkyard.

You change the oil, and you change the tires, and all of a sudden that works a lot better. So that may be what's going on here with aging. But the surprising thing is, at least in animal models, it's relatively easy to delay aging, and you get an accompanying benefit and healthy longevity as well.