Why do some animals live longer than others?

Andrew - It's a really great question. Actually, I think we can tie this into the bats that we were just talking about because the reason fundamentally for anything that happens in biology is evolution. And so if you look at an animal like a bat. Bats are sort of the same kind of size as a rat or a mouse, they're in the same sort of family, they're all very closely related species. But what you find is that the longest lived bats can live maybe 30-40 years in the wild. Whereas if you look at a mouse in the lab, they can live two, three years, maybe some of them, four years at the absolute outside. So what is it that the bats have learned to do in order to live that much longer period of time and crucially from an evolutionary point of view, what's driven that change. And actually I think in the case of bats is because they can fly and it's not just because flying is brilliant fun, or they want to press on and enjoy carrying on that lifestyle. It's because it makes them a lot, lot safer than mice. So imagine you're a mouse and you're going about your day. There are loads of dangers all in the world around you. There's there's cats that can kill you. There's infectious disease. You're a tiny little animal, so you can just die of exposure. You can just die of being too cold. And what that means is that when evolution is trying to set up your biology, it's not going to put a huge amount of energy into giving you elaborate anticancer defenses, because frankly, by the time you come down with cancer age, maybe two or three years as a mouse, you've probably already been eaten. Whereas if you're a bat, your flying up in the sky, you've got far fewer natural predators. You can fly to a nice warm caves, keep yourself cozy if the weather gets a bit cold. And what that means is evolution has had a lot more chance to evolve these anti-cancer defenses, defenses against heart disease, defenses against things like inflammation, which is one of the sort of molecular biological causes of the aging process. And that means that you can find animals that are surprisingly closely related, but nonetheless have these wildly divergent lifespans. So actually the irony is that the reason that you die of aging is because you can die of other things and the less you die of other things, the more evolution is incentivized to slow down your aging as a species.

Harry - That was a really nice definition there at the end of what that accumulates to. And my thought is, is in the lab, do we know Andrew of any species where we've been able to slow down this aging in the common mouse or rat? Have we been able to extend that lifespan

Andrew - Loads of different species. Yes. There are all kinds of what are called model organisms that we use in the lab. Obviously aren't humans, but have their various advantages to try and understand the fundamental biology. And we've slowed down aging in nematode worms, these tiny little millimeter-long worms that are often used in aging experiments, in flies, and obviously in mice, because they're the ones that are closest to human beings before you start getting into really big, difficult animals to work with like monkeys. And what you can do with mice as well, let's give an example. You can give mice drugs that are called senolytic drugs. And the reason they're so named is that they kill aged senescent cells, which are one of the fundamental underlying causes of aging that I talk about in the book. And as you accumulate these cells, as you get older, they basically accelerate the aging process. So the idea is that by taking one of these drugs, you can kill the senescent cells, but leave the rest of the cells in the mouses body, or hopefully in the future in humans bodies intact. And what that means is you basically make those mice biologically younger. So we gave these drugs to mice that were aged about 24 months, and obviously we just mentioned, mice are much shorter life span than we do, so that is sort of 70 ish in human years. And even though these mice are very old and they received the treatment, they basically got biologically younger. They lived a bit longer, but they didn't just live longer in ill health sort of stumbling along, unable to summon up the energy to die. They've got fewer diseases, they've got less cancer, they've got less heart disease, they got fewer cataracts and it wasn't just the diseases. They were less frail. They could run further and faster on the little mousy treadmills they used in these experiments. They always send the mice down the gym to sort of test their frailty. They were more curious. If you've got an old mouse in a maze and its anxious, maybe just a bit lazy, doesn't want to explore. And by removing these senescent cells, you could rejuvenate some of that youthful curiosity. And honestly, these mice just look great. I'm a computational biologist by training so I have never dealt with any actual animals in the lab. But even to my untrained eye, these mice look fantastic. They've got better fur, they've got better skin. They just look amazing.