Body Size and Longevity: The Paradox of Lifespan in Animals

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• The Size and Lifespan Paradox
• Naked Mole Rat Longevity Model
• DNA Repair and Cancer Prevention
• Metabolic Rate's Role in Aging
• Studying Long-Lived Species for Human Health
• Full Transcript

The Size and Lifespan Paradox

Dr. Steven Austad, MD, highlights a fascinating paradox in aging research. Between different animal species, a general pattern exists where larger species tend to live longer than smaller species. However, within a single species, the pattern is reversed. Dr. Steven Austad, MD, explains that smaller individuals, such as those in smaller dog breeds or smaller mice, typically have longer lifespans than their larger counterparts. This within-species pattern is the exact opposite of the between-species pattern, creating a complex puzzle for scientists to solve.

Naked Mole Rat Longevity Model

Dr. Steven Austad, MD, discusses the naked mole rat as an exceptional model for longevity research. This animal is roughly the same size as a common laboratory mouse but lives nearly ten times longer. Dr. Steven Austad, MD, notes that this extreme difference makes the naked mole rat an intriguing subject for understanding the mechanisms of slowed aging. He suggests that its unique underground habitat, which features low oxygen and high carbon dioxide levels, might contribute to its adaptations, though the exact reasons for its remarkable longevity are not yet fully understood.

DNA Repair and Cancer Prevention

Modern molecular tools are helping scientists pinpoint the reasons for longevity differences. Dr. Steven Austad, MD, explains that naked mole rats exhibit superior DNA repair capabilities compared to mice, though not as efficient as humans. They also possess advanced cancer prevention strategies. These intrinsic processes are critical areas of study. Dr. Steven Austad, MD, emphasizes that focusing on a handful of long-lived species, rather than just one, is essential. This approach, likened to triangulation, helps identify common mechanisms that could be applied to extend human healthspan.

Metabolic Rate's Role in Aging

The interview with Dr. Anton Titov, MD, explores the contested link between metabolic rate and longevity. Dr. Steven Austad, MD, has spent much of his career challenging the idea that a faster metabolism inevitably leads to a shorter life. He clarifies that while metabolism is a player in the aging process, it does not solely determine longevity. Dr. Austad provides the example of the giant tortoise, which can live 175 to 180 years despite an incredibly slow metabolism. This demonstrates that slow cell turnover and other factors are also critically important.

Studying Long-Lived Species for Human Health

Dr. Steven Austad, MD, outlines a strategic approach for translating animal longevity research to human health benefits. He argues that studying species with high metabolic rates that still achieve long lives, like the naked mole rat, is more informative for humans. For its metabolism, the naked mole rat lives longer than humans do, making it a valuable model. In contrast, a giant tortoise, for its slow metabolism, is actually shorter-lived than humans. Dr. Austad believes this comparative biology is key to discovering the best methods for extending healthy human lifespan.

Full Transcript

Dr. Anton Titov, MD: So that's very interesting, because you also note that generally animals with smaller sizes live longer. That's true in dogs: animals with smaller sizes live longer than animals with large sizes. But then there are some animals of similar size. For example, a naked mole rat has the same size but lives nearly ten times longer than a laboratory mouse. What could explain such differences in aging?

Dr. Steven Austad, MD: With all the modern molecular tools we have, I think we're starting to hone in on precisely that difference. I don't think we're there yet. Certainly, there are intrinsic processes that affect aging.

Naked mole rats, for instance, repair DNA better than mice do, though not as well as humans do. And we understand more about their cancer prevention strategies. But I think we are not yet sure why they live ten times as long as a mouse. It is an intriguing model, and I think it's a model for what we need to do next.

We can't just focus on one long-life species, though, because that's liable to tell us something that's very idiosyncratic to that species. For instance, naked mole rats live underground. They live in a low oxygen, high carbon dioxide atmosphere. Whether that has anything to do with their adaptation or not, we don't know.

I think what we need to do is focus on a handful of really long-life species, to try to think of it as triangulating in on the best methods for working to extend human health.

By the way, I wanted to point out something that you mentioned earlier, and I think it is a source of confusion—something that I struggle with when I'm talking about aging with people. If you look at individual species, there's a general pattern for large species to live longer than small species. If you look within a species, there's a general pattern for smaller individuals to live longer than larger individuals. Smaller dog breeds live longer than larger dog breeds.

Smaller mice live longer than larger mice. Smaller horses live longer than larger horses. So the within-species pattern is the exact opposite of the between-species pattern.

Dr. Anton Titov, MD: So that's fascinating. What do you think can explain this sort of interspecies versus within-species differences in lifespan? Because the metabolic rates are supposed to be more similar within the same species, is it not?

Dr. Steven Austad, MD: Yeah, I've spent a lot of my career trying to kill this idea that metabolism is inevitably linked to longevity. But in thinking about it, it's not running the show. It doesn't determine longevity, but certainly metabolism is a player in longevity.

And so I think when we think about species that we can learn something from, we really need to think about species that have a high metabolic rate because they're suffering more intracellular damage potentially than species with a low metabolic rate. For instance, we know that giant tortoises live 175 to 180 years, much longer than people, but they have an incredibly slow metabolism.

And so my thought is, in slow cell turnover, I thought we're unlikely to learn something about extending human health from studying something like a giant tortoise. Whereas we are studying something like a naked mole rat because, for its metabolism, it lives longer than humans do. Whereas for its metabolism, giant tortoises are shorter-lived than humans.