When we hear of scientists researching drugs that ‘reverse ageing’ it can conjure up two very different images. One is a barely credible cosmetic advert, showing the stunning wrinkle-reducing power of the newest face cream, and the other is of mad professors seeking the key to eternal life. In reality, although eternal life is a bit far-fetched (no drug can make us indestructible), a drug that increases the health-span – that is the amount of time we stay fit and healthy – would be an important step forward for improving quality of life and public health. Recent work from Dr Peter de Keizer’s lab in the Netherlands, widely reported in mainstream media, may have brought us one step closer to this goal. But how excited should we really be that perpetual youth is within grasp?
To counter ageing we must first ask, what is its root cause? During normal function, the cells that comprise organs die, and are replenished with fresh cells from precursor cell sources. One theory of ageing is that over time, non-functioning cells – that should have died – stick around and release signals that harm neighbouring cells. This is known as ‘senescence’. The accumulation of these senescent, non-functioning cells in our tissues manifests itself as old age. To reverse this process, then, a logical approach would be to target senescent cells for destruction, allowing fresh new tissue to grow.
To design a drug to kill senescent cells, we need to first identify some key features unique to them. The Keizer lab looked at differences in gene activity between normal and senescent cells, and identified a gene called FOXO4. Further studies established that FOXO4 was keeping senescent cells alive by blocking a process called ‘apoptosis’ – the cellular equivalent of suicide. The researchers designed a drug that mimicked FOXO4 but lacked its function. When administered, the drug replaced FOXO4 which allowed apoptosis to happen and killed the cells. They tested the drug both in old mice, and in mice that age quickly due to genetic abnormalities, and found some striking differences. These differences included improvements in the quality of their fur, their physical activity in a running wheel, and their kidney function.
So what does this mean for perpetual youth? Well, if the development of anti-ageing treatments like this one continues, we could be boxing and mountain biking well into our 90s. However the effects of the drug on the function of other organs, such the brain or the heart, are still unknown, and it could possibly have a negative impact. Also some effects, such as improvements in physical activity, were only observed in fast-ageing mice and not naturally aged ones. As always, the raw data is perhaps less exciting than the headlines suggest. Nevertheless, there are real signs of improvement in aged mice, and no indications of adverse side effects. Even if this drug doesn’t make us forever young, it may make us forever slightly less old. But as is always the case with age, only time will tell.
This article was written by Isaac Shaw and edited by Bonnie Nicholson.