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For Scientific American Science Quickly, I'm Rachel Feldman.
In the animal kingdom, lifespans can stretch from mere hours to entire centuries.
But that's just the start.
Some creatures deteriorate so slowly that we've never actually caught them dying of old age.
Others don't seem to age at all.
And some can apparently reset their biological clocks and bounce back to infancy to start all over again.
Plenty of humans would like to figure out how that works—and potentially harness the ability for our own use, but science has a long way to go.
The truth is that we barely understand why or how we age in the first place, let alone how we might stop it.
My guest today is Jean -Petro Magalhães.
He's the chair of molecular bio -gerontology at the University of Birmingham in England, and he's here to tell us all about the nascent science of aging.
Thank you so much for coming out to chat today.
My pleasure. Thank you for the invitation.
So, I'm sure that all of our listeners know that different species have different lifespans.
But could you start by giving us a sense of some of the extremes that are out there?
It's been a mystery of biology for a very long time, ever since Aristotle noticed there's differences in lifespan across species.
And we know that some animals have very short lifespans, others have very long lifespan.
And this happens even amongst closely related species like mammals.
For example, hamsters live about two years, mice and rats can live up to three or four years and, of course, humans, we can live over 100 years.
And then at the end of the spectrum, we have certain species of whales that have been estimated to live over 200 years.
So it is quite remarkable how much of a variation in longevity there is.
And then besides the mammals, I would assume that things get even more extreme when you're talking about less closely related species.
Well, there's some very unusual animals.
There's this type of jellyfish which appears to be immortal or appears to have the ability to rejuvenate, to go back in biological time.
So adults can go back to earlier stages of development and start again their own lives.
So it's not that they're immortal that you can't kill them, but they are biologically immortal in the sense that biological time for them doesn't row in one direction like it happens for us.
So there's very unusual animals – again, we're talking invertebrates like rotifers or very simple animals – whose adults don't have mouths.
They don't have a way of feeding.
So there are very clear examples of mechanical limitations that will result in the demise of organisms. So you have a very big variety in terms of not just longevity and paces of aging, but even in aging phenotypes and how species degenerate and die.
And fundamentally what is aging?
So aging, we're all familiar with it.
I tend to have a very broad definition of aging as a progressive and inevitable physiological degeneration and increase in vulnerability and decrease in viability.
Now of course there's many facets to aging.
I mean it involves physiological degeneration.
I mean our bodies get weaker.
We become thriller with age.
But there's also of course many cellular molecular changes that occur as well.
And then of course, there's increased incidence of diseases, cancer, cardiovascular diseases, neurological diseases, and so on.
So one of the hallmarks of aging is that once you reach about age 30, your chance of dying double roughly after eight years, and that's very consistent across populations.
And that happens as well in animals only, in animals like mice.
It varies a bit between strains, but it really is something like every few months, the chance of dying doubles.
And what do we know about what causes aging?
Why is it inevitable for most species but then for some, like those jellyfish, doesn't seem to be?
Well, that's the big question and we don't have a good answer yet.
We don't have a good understanding of why some species age very fast. So, for example, mice and rats, as I mentioned, they only live up to three or four years, But they also age much faster than human beings, no matter how you take care of them, the mouse will age about 20, 25, 30 times faster than a human being.
So we know there's a very big diversity also in rates of aging.
But what's behind it is not well understood.
We know there must be genetic differences, again, because no matter how well you take care of your mouse or hamster or rat, it will age a lot faster than a human being.
So, you can let it watch Netflix all it wants, it will still age much faster than human beings.
So, there have to be genetic differences.
It's not the environment, it's not the diet, it has to be genetically determined, it has to be encoded in our genomes how fast we age.
But then, of course, the question is, okay, what is the biochemical molecular cellar determinants?
That's something we don't understand well yet.
Having said that, there are some hypotheses.
For example, one idea that's been around for decades is the idea that damage to the DNA And mutations in the DNA accumulate gradually with age and then cause aging.
And the hypothesis being that in mice, for example, this accumulation of mutations occurs much faster, for which there is some experimental evidence.
So that is one hypothesis.
And at the moment, however, it's still unproven and known really why human beings age.
Hmm. And are there any factors that long - living organisms have in common?
And there are multiple factors associated with long lifespans.
I mean, the important point is that we are a product of our evolutionary history.
Of course, we now have technology and we have medicine, but we didn't evolve in these conditions.
We evolved as cavemen hundreds of thousands or millions of years ago.
And the same for all of the other species.
And so the main determinant of whether a species evolves in short lifespan or a long lifespan is extrinsic mortality.
So how much they die of.
In particular, predation.
So if you have animals like short -lived animals like mice, I mean, mice in the wild very rarely live more than one year not just because of diseases but primarily because of predators.
And because they have very short lifespans, even in the wild, then they have to grow very quickly.
They have to develop very quickly and they have to reproduce very quickly.
And so everything happens very quickly.
So it's a very fast life history and very fast lives that they live.
On the other hand, humans or the Galapagos Tortoise would be an example, or big whales, or underground subterranean animals like mole rats, they're protected from predators.
I mean, we are protected from predators, one, because we're relatively big for primates, and of course because of our intelligence.
Which allows us to escape predators when we were, of course, in the time of cavemen and when we were evolving.
And that means that because we have fewer predators, we're top of the food chain, that means that we have more time to grow, to develop, and then of course that leads to a longer lifespan as well.
So cross -species, there's this pattern, of course, of, you know, we are a product of our evolution, and we have the life history and the longevity that fits our evolutionary history.
What kinds of tools are researchers using to try to answer all of these questions we have about aging and lifespan?
So there's different types of tools we can use.
One big technological breakthrough was DNA sequencing.
We can sequence DNA relatively cheaply and relatively rapidly nowadays.
The human genome sequencing costs billions of dollars, but nowadays you can sequence your own genome.
Anyone can sequence their genomes for a few hundred dollars.
So it's relatively cheap to sequence genomes, which means we can also sequence the genomes of different species, species with different lifespans.
So for example, our lab, we sequenced the genome of the bowhead whale, which is the longest -lived mammal that's been estimated to live over 200 years.
As well as naked mole rats and other long -lived disease -resistant species.
And there's now hundreds of genomes sequenced from many different species with different lifespans.
And so what you can do with that trove of information is analyze it for patterns associated with the evolution of longevity.
You can ask questions, so for example, do species that live a longer lifespan, do they have more DNA repair genes?
So you can use that information on the DNA to study the evolution of longevity, then try to find specific genes and pathways associated with it.
Now, the other approach we use to study aging, of course, is in model systems. I mean, unfortunately, we cannot really study aging in human beings, or we can, but it's very difficult and time consuming.
And so we tend to use short -lived model systems like mice, or fruit flies, or worms. Worms live a few weeks.
We tend to use fruit flies.
Drosophila, they live a few months.
Mice can live up to three, four years.
So we can study these animals to try to gather insights into the mechanisms of aging, hoping that some of these will be applicable to humans.
I mean, there's some rationale for it because we know the basic biochemistry of life in a mouse is quite similar to humans.
We can also manipulate aging to some degree in animal models, particularly at the genetic level.
We can tweak genes in animals, including in mice, and extend their lifespan.
In mice, it's up to about 50%.
But for example, in worms, we can tweak a single gene in worms and extend by about 10 times, which is quite remarkable.
So we can do a lot of studies in animal models.
we can manipulate aging to some degree in animals, and then we can do mechanistic studies.
We can look at their molecules, we can look at their cells, we can look at their hormones, and try to test mechanistic hypothesis of aging.
What do you think are the biggest questions that we should be tackling about human aging and human life spans?
Well I suppose the big question is still why we age.
I mean, why do human beings age?
As I protein homeostasis?" There's different hypothesis, but we still don't know why we age and I think that remains the big question in the field.
There's other questions, of course.
Can we manipulate human aging?
Because although we can manipulate, to some degree, aging in animal models, we don't know if that's possible or not in human beings.
We can manipulate, to some degree, our longevity by exercise, eating healthy, not smoking, not drinking too much alcohol and so on, But whether, for example, can we develop a longevity drug?
There's a number of companies and labs trying to develop longevity pills.
But whether they're going to be effective in humans, that's still something that's up to discussion and will require, for example, clinical trials.
So one aspect that's quite fundamental and important in aging is that there are complex species, like some species of reptiles like the Galapagos tortoise, some species of fishes like rock fishes, some species like salamanders that appear not to age at all.
There's no mammals in this category.
There are complex vertebrates that, in studies spanning decades, do not exhibit increased mortality or increased physiological degeneration.
That is quite a fascinating observation that some species do age after a very long time, but at the very least, they age much, much slower than human beings, which I think is a great inspiration as well.
Because for example, just like the Wright brothers took inspiration from birds.
They saw birds. Well, birds are heavier than air and yet, they can fly.
So there's no reason to think we cannot build the machine that's heavier than air and can make us fly.
We can take inspiration for these animals.
There's no physical limit that imposes that every organism has to age.
And so we can take inspirations from the species that appear not to age and think well maybe with technology and therapeutics we can at the very least slow our aging process.
Thank you so much for coming on to talk today.
This has been great.
Well thank you. My pleasure.
That's all for today's episode.
We'll be back on Friday.
Science Quickly is produced by me, Rachel Feltman, along with Fonda Mwangi, Kelso Harper, Naima Marsi, and Jeff D 'Alessio.
This episode was edited by Alex Seguiara.
Shayna Posis and Erin Shattuck fact -check our show.
Our theme music was composed by Dominic Smith.
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