I’ve spent enough time working in A&E to know that living longer and living well are two very different things.
Take two recent patients of mine. One died at 96 after a wonderfully healthy life and only a very short final illness. The other died at 73, having suffered from diabetes and dementia since they were in their 60s.
The 23-year difference in their ages tells only part of the story. The other difference is between lifespan (how long we live) and healthspan (how long we remain well).
Of course, how we age depends on our lifestyle, our socio-economic circumstances, the genes we inherit and plain luck. But while we can’t change the genes we have, there is increasing evidence to show that the way we live can affect the way those genes behave.
That is why a study published in the journal Nature just two weeks ago is so exciting. It went under the radar, even though its findings are remarkable.
It found that semaglutide, the active drug in the weight-loss jab Wegovy, significantly extended the lives of old female mice.
It also improved their memory and physical performance and – crucially – changed the activity of genes involved in ageing – turning down some processes that damage cells and turning up others that help to keep them healthy.
The researchers at the University of California, Berkeley, started treating the mice when they were 20 months old, an advanced age for these animals, which normally live for around two to two and a half years.
A study published in Nature two weeks ago showed that semaglutide, the active drug in weight-loss jab Wegovy, significantly extended the lives of old female mice
For the experiment, 40 mice received daily semaglutide injections and 39 received salt-water injections for the rest of their lives. The results showed that semaglutide increased typical lifespan by 92 days on average.
For a mouse, that’s a significant amount of extra time – about 12 per cent longer – even though treatment only began when they were already old.
While the dose was broadly equivalent to that given to people having weekly Wegovy jabs, mice and humans process medicines differently, so we do not know whether the same dose would have the same effects on people.
But there’s an even more important point. Longevity medicine isn’t simply about keeping us alive for longer if it means those extra years are spent frail and ill.
Yet when the researchers tested a separate group of old mice after three months of semaglutide treatment, they performed better in tests of memory, co-ordination and endurance.
For instance, in one memory test, they found an escape hole in less than half the time of a placebo group, and they could run for almost three times as long before becoming exhausted.
But what really caught my attention was the effect of semaglutide on genes in the mice’s liver cells – making those linked to inflammation less active, while others involved in repairing DNA and clearing away damaged proteins became more active. That matters, because long-term inflammation and the build-up of damage inside our cells are two of the reasons our bodies deteriorate as we grow older.
The drug also raised levels of NAD – nicotinamide adenine dinucleotide. This compound helps our cells produce energy and repair damage, but levels fall as we get older.
Plus, it made sirtuin genes more active. Sometimes called ‘anti-ageing genes’, these help our cells use NAD to cope with stress and repair damage.
Forty mice had daily semaglutide injections as part of the study, while 39 had salt-water injections – those on semaglutide lived an average of 92 days longer than the typical lifespan
Put all this together and semaglutide appeared to turn down processes that damage cells and turn up those that help maintain them. This might explain why the treated mice not only lived longer but remained healthier.
There is another crucial question: Could the effect be down to the mice on semaglutide simply eating less and losing weight?
In fact, in a separate experiment by the same researchers, comparing semaglutide with a diet containing 24 per cent fewer calories, both approaches led to mice losing similar amounts of weight and fat.
However, semaglutide produced better results in measures such as memory and blood-sugar control. That suggests the drug may be doing more than simply causing weight loss.
Studies in humans point to something similar.
A landmark trial in the New England Journal of Medicine in 2023, which looked at 17,600 people who were overweight or obese with cardiovascular disease, found that those given weekly semaglutide reduced their risk of a heart attack or stroke, or dying from cardiovascular disease by 20 per cent over the following three to four years.
A later analysis found that much of this benefit could not be explained simply by weight loss. It could be because semaglutide reduces inflammation, blood pressure, blood sugar and blood fats. But the truth is, researchers still do not know exactly why it protected the heart.
Another major trial found that semaglutide slowed kidney damage and reduced deaths among people with type 2 diabetes and kidney disease.
So we have strong evidence in humans that, beyond weight loss, this drug might help us remain healthier as we grow older.
It may even delay ageing. Another study, published in May in the journal Nature Communications, involving patients with HIV and excess abdominal fat, looked at DNA methylation – chemical marks on our DNA that can give an indication of how quickly the body is ageing.
And guess what – semaglutide slowed this process (even when HIV is well controlled, sufferers can have ongoing inflammation and signs their bodies are ageing more quickly, which is why these patients were studied).
So could semaglutide be used one day to extend both our healthspan and our lifespan? Potentially. But it’s not the first treatment to raise that hope.
Metformin, the common diabetes drug, is one of the best-known examples, with some animal studies suggesting it led to a small increase in lifespan, although this has not been shown in humans.
Then there’s NMN (nicotinamide mononucleotide), a substance our bodies make naturally and which is found in tiny amounts in some foods.
Early studies in 2024 found it delayed frailty in mice and kept some muscle genes behaving more like those of younger animals. Females also lived 8.5 per cent longer (although male mice did not).
So where does all this leave us? Well, if you’re otherwise healthy and normal weight I don’t think you should immediately start taking Wegovy in the hope of living longer – we’ve not yet had any human trials showing it can extend life or keep us healthier for longer, and these drugs can have side-effects.
But we do now have animal data on semaglutide’s benefit for ageing – and strong evidence of wider health benefits in humans. And this is a drug we already use safely in obesity. So it does feel like we could be at the start of something very special.
And if semaglutide could help more people live like my 96-year-old patient, enjoying their families and the things they love and remaining well until very near the end, then its potential as an anti-ageing drug needs serious investigation.
And yes, even healthy, slim people may end up taking it.
@drrobgalloway
