Why do we die? A Nobel Prize-winning biologist explains

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Indian-born, American-British structural biologist Venki Ramakrishnan explains the ageing process and the new technologies that might help us slow it down. Photo / Getty Images
Venki Ramakrishnan explains the ageing process and the new technologies that might help us slow it down.

Ageing is a big existential question and, as far as we know, we’re the only species aware of our mortality. For most of our existence, there’s not been much we
could do about it. But biology has made tremendous steps forward in the past few decades in understanding the processes behind ageing and, ultimately, how we die.

We now know ageing is an accumulation of changes and damage to the molecules in our cells, and when that leads to a breakdown in critical systems – such as our brain, heart or lungs – the result is death.
Before we can think about how we can live longer, we first need to understand how we age, which is driven by many interlinking factors.
Firstly, DNA (our genetic material) accumulates chemical changes or damage that alter the way in which our genes are read. Then, the end of our chromosomes shrink, which can lead to a process called senescence which occurs as we age. This is when our cells no longer function normally and start secreting molecules that cause inflammation.
Senescence is a particular problem for stem cells, which are vital for regenerating and replacing cells in our tissues, including muscles, skin and connective tissue.
While this all sounds quite technical, if we understand these processes, the question becomes – can we slow any of them down? That’s what biologists are trying to do.
The wealth of investment into this space has led to much hype but we should be realistic. Immortality is impossible since, even if you slow down ageing, there are many other causes of death such as disease or accidents. And I don’t think we can extend life dramatically given current technology.
Instead, the goal of research in this space is to find out how we can live a larger fraction of our lives in better health. After all, age is the biggest factor in many diseases we acquire: Type 2 diabetes, cancer, heart disease and dementia. If we find out how to slow down the ageing process, we may postpone the onset of these diseases.
How it could be taken: A pill
Lots of research in animals shows that, if they can gorge on as much food as they like, they don’t live as long as those whose calories are restricted to only what they need to survive.
We think this is because calorie restriction affects our metabolism, in part by turning down the body’s protein production and turning up its protein recycling capabilities, both of which are beneficial for healthy ageing.
While few have the willpower to restrict their calories to achieve this, a drug known as rapamycin that is given to cancer and transplant patients mimics this effect.
However, it leaves users more prone to infections and causes other side effects. So, scientists would need to work out a way of administering this drug, or a similar one, so it doesn’t cause unwanted harm.
How it could be taken: An infusion
In a bizarre series of experiments, researchers found out that connecting the blood systems of an old and young mouse benefits the health of the older animal.
As a result, researchers are trying to find out what exactly could be in young people’s blood that could have an anti-ageing effect. Maybe young blood is less prone to inflammation or activates stem cells, which are involved in regeneration of tissues.
Some people are jumping the gun (notably Bryan Johnson who once had blood infusions donated by his 17-year-old son) and companies sprouted up offering to set up transfusions – taking blood from young donors and giving them to rich older people. Their argument is that customers are not willing to wait for clinical trials. While this is a promising area of research, this is a dangerous way of doing things.
How it could be taken: A pill or infusion
When our bodies sense that a cell has been damaged, it tries to repair it. If this doesn’t work, the cell is killed (a process called apoptosis) or “switched off” (referred to as senescence).
However, while the “switched off” cells can’t work as normal, they secrete inflammatory molecules in a bid to sound the alarm that it needs to be cleared away.
When we’re young, this is a vital process. However, as we age, more of our cells go into senescence, while our ability to clear them worsens. This accelerates ageing.
Experiments in mice show that killing senescent cells reverses some symptoms of ageing. This has led to a field called senolytics which is looking for drugs that can do this in humans. Again, while promising, this is in its early stages and will be a complicated thing to figure out – you don’t want a pill or infusion that also zaps healthy cells or has toxic side effects.
How it could be taken: Gene therapy
Normally, a fertilised egg develops into more specialised stem cells which then develop into all the cells in our body. In this challenging but exciting area of anti-ageing research, the idea is to trick cells in our body to go backwards in development and become stem cells, which can help with regenerating tissue as we age.
There are four proteins (called Yamanaka factors) which can cause those final cells to go backwards and become stem cells. If successful in humans, exposure to these proteins could help rejuvenate our tissues and reverse many of the effects of ageing.
While this has shown promising results in animals, research so far has also found that the process can also increase the risk of cancer. Scientists still need to figure out how to offer this safely and how to target specific organs. It is also difficult to carry out. Currently it is done by introducing the Yamanaka factors via special viruses, or by directly introducing them into the genome of animals.
Some supplements, such as chemicals that help the body to make nicotinamide adenine dinucleotide (NAD+) have shown promising results in animals. But we need large-scale trials in people to show it is safe and effective over the long term. Currently, there aren’t any pills for anti-ageing that meet the rigorous standard of most medicines.
Instead, there is a three-legged stool that is completely free and has no side effects, yet can prolong your health in old age.
The first is diet. Instead of the modern all-you-can-eat approach, your diet should be moderate with lots of plants and fibre – think vegetables, fruit, legumes, nuts and seeds. It’s also worth cutting back on ultra-processed food as much as you can (those that contain ingredients you wouldn’t find in your kitchen cupboard, such as emulsifiers and preservatives).
Some studies support leaving a 12-hour gap between your final meal of the day and your first meal of the next, though this may just be because it results in our eating too much overall, which is known to be bad for our health.
The second leg is exercise. We need cardiovascular exercise (150 minutes a week of activities such as running, cycling or swimming) to strengthen our heart, while resistance exercise that engages the upper and lower body increases our strength – vital as we get older and lose muscle, which leaves us more frail and prone to falls.
The third leg is sleep, as this is when a whole lot of maintenance and repair occurs.
This combination, though predictable, is better than any pills on the market, it doesn’t cost a thing and the only side effects are beneficial ones.
It’s also important to avoid stress, where possible, and that includes not obsessing about ageing, which can be a source of stress. Finally, getting yearly checkups for cholesterol, high blood pressure and diabetes will help because there are good treatments for these conditions.
Saying that, if somebody offered a perfectly safe pill that would give me an extra 10 years of healthy life, I would probably take it.
As told to Emily Craig
Venki Ramakrishnan’s book, Why We Die: The New Science of Ageing and the Quest for Immortality, was published in March.
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