By Prof. Daniel M. Davis | 2 May 2022
Is there any way to avoid the decay and frailty that come with age? Jeff Bezos thinks so. A biotech company that the founder of Amazon has helped fund, Altos Labs, is said to have $3bn at its disposal to research ways of holding back the clock. Closer to home, scientists at the Babraham Institute in Cambridge recently announced they had altered a 53-year-old woman’s skin cells so they behaved as though they were 30 years younger.
An expert on how and why we age.
"Our genetic material is modified over time – chemicals can be attached that change which genes are switched on or off." https://t.co/Jh52fnxIlT
— The Conversation (@ConversationUK) January 23, 2022
Promising as this may seem, it’s a long road from the lab to the clinic. But the difficulty of translating scientific breakthroughs into treatment hasn’t stopped an explosion in research. To understand why the once fantastical idea of preventing or reversing ageing is even considered a possibility these days, we need to appreciate exactly what happens as we get older.
The human body is made up of cells in a constant cycle of life and death. Different types of cells have their own inner clocks, determining how long they live. Sperm cells live about three days, while some brain cells last a lifetime. The upper layer of skin which you can see and touch is regenerated every 30 days or so. As time goes by, however, many types of cell in the human body become less good at reproducing themselves by dividing. Skin cells from a newborn baby can divide 80 or 90 times, but cells from an elderly person divide about 20 times before they stop. So one reason we age is that our cells age. But other things are happening too: we become wrinkly because elderly skin cells produce less collagen and elastin, and sebaceous glands produce less oil. Surface bruises happen more easily because blood vessels become fragile. Ageing is multifaceted.
One thing we do know is that there isn’t actually a hard biological limit to how long we can survive. Some animals live much longer than we do. Jonathan, for example, is a 190-year-old giant tortoise from the Seychelles. Other tortoises might be even older, but Jonathan is recognised by the Guinness World Records as the oldest living land animal because there’s a photo of him in his heyday aged 50, munching on grass. Bowhead whales can live for more than 200 years and some sponges are thought to survive for more than 2,000. The oldest human whose age has been verified was Jeanne Calment, who died in 1997 at the age of 122, outliving her grandson.
190-year-old Jonathan becomes world's oldest tortoise everhttps://t.co/QHmgEaSEk3
— Travis Akers (@travisakers) January 17, 2022
Although Calment’s grandson wasn’t as lucky as her, long lifespans like this do tend to run in families. Twin studies appear to show that the genetic contribution to longevity is around 25%. Astonishingly, genetic mutations in nematode worms, which normally live for about three weeks, can increase their lifespan by up to 10 times. Needless to say, nothing like this is possible for humans. Instead, hundreds of human gene variants are linked to ageing, each having a small effect on their own, but combining in complex ways. Deciphering this picture will require the efforts of all kinds of scientists, including biologists, physicians, mathematicians and computer scientists. This is an area where having a big budget really does help.
There is a lot we still don’t know about genes and ageing but, as we’ve seen, it is possible to manipulate genes to make cells become young again in a lab dish. In the mid-2000s, Japanese scientist Shinya Yamanaka showed that the introduction of four genes – the Yamanaka factors – into adult cells caused them to revert to stem cells normally found in embryos (and capable of becoming all the different kinds of cells in the human body). Today, researchers are seeking ways to control this process more finely, to use Yamanaka factors to roll back the age of cells, or repair damaged tissues, without them going all the way back to an embryo-like state. This appears to be what the team at the Babraham achieved, by exposing aged skin cells to Yamanaka factors for a relatively short period. Important problems remain, however, because the very same factors which make cells young again can also make cancer more likely.
— Paul Brackley (@PaulBrackleyCI) April 14, 2022
There are other ideas on the table for combating ageing. We could, for example, directly clear away old cells that are causing problems. Cells that remain alive but have stopped dividing are deemed “senescent”. These senescent cells accumulate in the body over a lifetime – especially in the skin, liver, lungs and spleen – and have both beneficial and detrimental effects. They are beneficial because they secrete factors which help repair damaged tissue, but as senescent cells increase in number, they can disrupt the normal structure of organs and tissues. Mice in which senescent cells were cleared away took longer to show signs of ageing.
Nobody knows the extent to which Altos Labs, or any other organisation, is going to solve this puzzle. But what is clear is that there will be spin-offs from the effort, such as new ways of aiding tissue repair, fighting cancer, or boosting immunity. A crucial point here is that the mission to beat ageing has a vastness to it in the same way that landing on the moon wasn’t just about landing on the moon; it is a journey which will lead to all sorts of new technologies, scientific knowledge and medical outcomes.
The worms provide a note of caution too. Those long‑lived genetic mutants have a much extended period of frailty, which emphasises the importance of focusing on increasing not just lifespan, but healthspan. Beyond that, ageing isn’t just a personal issue: it is entwined with social, economic, psychological and other concerns. Should we, for example, work until our 70s or 80s? How will we ensure equality when the rich already live longer than the poor? Perhaps the most pertinent question of all, to which each of us must find our own answer: what will be our purpose? What would make us happy, in those extra years?
Reprinted with permission from the author.
My new book is out today! THE SECRET BODY. The cover has wonderful comments from Bill Bryson, @ProfBrianCox @theAliceRoberts @DoctorChrisVT and Venki Ramakrishnan. Please do check it out! pic.twitter.com/3fhne3kKK9
— Dan Davis (@dandavis101) July 1, 2021
Daniel Davis: A short history of scientific revolution in immunity
How The Ultra Rich Are Trying To Live Forever – CNBC News
Science rejuvenates woman’s skin cells to 30 years younger – BBC News
Decoding the secret of aging | DW Documentary