4 Apr 2024

Venki Ramakrishnan on the science of ageing

From Nine To Noon, 10:05 am on 4 April 2024
Venki Ramakrishnan's new book looks at the growing anti-ageing industry and whether we should be trying to live much longer lives.

Photo: Supplied / Hachette

Frustrated by the excessive hype around anti-ageing, molecular biologist Venki Ramakrishnan presents the facts in his new book Why We Die: The New Science of Ageing and the Quest for Immortality.

With our fear of death fuelling a sense of urgency, "solid science" can often get lost in the hype, the Nobel Prize winner says.

"The impression is the stuff is all going to happen tomorrow. It's just around the corner. And I'm very sceptical that that's true. I think it'll take a lot of effort and quite a bit of time," he tells Kathryn Ryan.

Sir Venki Ramakrishnan won the Nobel Prize in Chemistry in 2009. He was president of the Royal Society - the oldest scientific academy in the world - from 2015 to 2020.

Ever since humans became aware of mortality, we've wondered why it is that we have to die, Ramakrishnan says.

The recent explosion of research and money being spent on anti-ageing is partly due to the interest of tech billionaires, he says, but also because governments and societies are struggling with the idea of how to keep a booming older population independent and preferably productive.

The ageing process is effectively "an accumulation of damage" on a cellular and eventually a tissue level, Ramakrishnan says.

While our bodies have extensive mechanisms to both repair this damage and get rid of damaged components, over time those repair systems themselves break down and when they do the damage starts accelerating.

"When the DNA in a cell gets damaged, the mechanism in the cell senses the damage and if the damage is moderate, it tries to repair it.

"If the damage is considered to be too much, then what the cell does is it chooses one of two pathways.

"One [pathway] is to force the cell to commit suicide. You might think that's a bad thing but actually we have trillions of cells and we can afford to lose plenty of them. What we can't afford is to have a cell become cancerous because that can kill the whole organism. So nature has evolved this method of sending cells off to commit suicide."

The other pathway cells take is towards 'senescence', aka deterioration.

"Senescent cells are cells that have stopped dividing, but they don't just stop dividing, they also send out signals, they send out inflammatory molecules which attract cells of the immune system to the site of damage ... What serves a purpose early on also results in ageing later because as we accumulate senescent cells, we then suffer from inflammation as a result of the accumulation of senescent cells. And the accumulation itself is a problem."

When it comes to regenerating cells that are on this path, an anti-fungal agent called rapamycin is currently "something of a darling" amongst anti-ageing researchers, Ramakrishnan says, although it does have serious side effects.

"Because [rapamycin] suppresses your immune system, you're more prone to infections, you won't heal wounds as well.

"So the question is, could you find a dose where it's beneficial but without having the side effects? Or could we find a molecule similar to rapamycin which might work better? A lot of focus of some parts of the ageing community is on [finding] that molecule."

Determining the difference between young blood and old blood is another big field of research, Ramakrishnan says, with some US companies taking the plasma from the blood of young donors and selling it to rich people for transfusions.

Research into stem cells - the foundational cells which create and regenerate different parts of our bodies - is another promising area, he says, although it presents "real risks".

"As we get older, these stem cells are depleted from our body … they're not as diverse and they're not as functional as they were when we were young.

"The question is could you take a fully developed cell and turn it back into a stem cell to help tissue regeneration and improve many of these symptoms? If you don't do it just right, you have a serious risk of developing cancer.

"The other issue is that the different parts of our bodies don't age at the same rate. One organ might be biologically older than other organs, and so on. How would you apply this treatment without incurring risk? It's a challenging problem."

The jury is still out on whether or not humans can live with a degree of health beyond the age of 120, Ramakrishnan says, "but there's no law against it".

He's concerned about the societal impact of such a development.

"I personally think it would result in a somewhat stagnant society where older people had even more power than they do now. And it would also create enormous social disparities. Already the richest 10 percent live a decade or sometimes almost two decades more than the poorest 10 percent. They also live a higher fraction of that life healthy compared to the poor.

"I'm not saying all of this has to happen. But I do think that people are not talking about it. They're simply acting as if [living as long as possible] is a universal good.

"We have a world where people are still dying of malnutrition, infectious diseases, all kinds of things, childhood diseases. So where do we best allocate resources? That's also a very legitimate question."