Suppressing a hormone that governs metabolism boosts your chances of living to a grand old age, but there’s a downside
Would you be prepared to sacrifice your fertility in order to live longer? It’s an almost inconceivable dilemma, but one day we could be offered a choice between having children and enhancing our chances of reaching a grand old age.
The idea that fertility and longevity may be intertwined was first mooted in the 1970s when gerontologist Tom Kirkwood, now at the University of Newcastle, proposed his “disposable soma” hypothesis. Over time, our bodies age as a result of natural degeneration or “wear and tear”, and Kirkwood suggested that they have a limited energy budget that can either be used to repair damaged cells and halt this decline, or saved to allow us to reproduce.
Thirty years on and advances in genomic techniques have enabled scientists to pinpoint one of the key molecular pathways involved in the ageing process, controlled by a hormone known as IGF-1 (insulin-like growth factor 1).
The link between this particular hormone and longevity was uncovered almost by chance, while biologists were studying the behaviour of a species of worm known as Caenorhabditis elegans. Worms have a special mechanism that kicks in when they’re exposed to severe environmental stress: their levels of IGF-1 drop, putting them into a state of hibernation during which they’re unable to procreate. But, crucially, they stay alive.
In all mammals, including humans, IGF-1 is believed to initiate a chain of events that controls the way energy is used. There are genes involved that stimulate proteins to begin vital processes such as the repair of damaged cells, which can have a big impact when it comes to postponing the onset of cancer, for example.
However, the type of processes that are initiated depends on the levels of IGF-1, with low levels sending the body into a self-preservation mode, switching energy allocation away from the reproductive organs and devoting resources to maintenance and DNA repair.
Having low levels of IGF-1 can make a big difference when it comes to avoiding some of the most common degenerative illnesses in later life, and we’re now getting some fresh insights into how this might work for Alzheimer’s disease. This month, psychiatrists from the VU University of Amsterdam report their investigation into the link between IGF-1 and this form of dementia. They found that high levels of IGF-1 in the blood of middle-aged people was associated with a high genetic risk of getting Alzheimer’s – the first time such a link has been found in humans. They believe that reduced activity of the hormone prevents the disease from developing.
“Alzheimer’s disease in late life is probably driven strongly by spontaneous low-grade inflammation in the brain,” explains longevity researcher Maarten Rozing from Leiden University in the Netherlands, who wasn’t involved in the research. “So low IGF-1 activity would mean far more molecular activity being devoted to repairing damaged tissue, which can halt the inflammation and prevent it from spreading.”
There is more evidence linking low IGF-1 activity and healthy ageing. A recent study looking at centenarians in the Ashkenazi Jewish population of New England found an intriguing genetic link: they were more likely than the general population to carry mutations that reduced the activity of IGF-1.
However, far from being a matter of genetic fate, it may actually be possible to proactively influence the level of IGF-1 in our bodies, since it is related at least partly to diet. Some researchers believe that low-calorie or even low-protein diets can be beneficial, and calorie restriction experiments with mice, starting from birth, have yielded positive results in terms of survival benefits.
“You see the mice living up to 40% longer and [they] are much healthier,” Rozing said. “However, it’s a little more difficult to examine this in humans, simply because they live so long! But some experiments have shown that calorie restriction can lead to metabolic benefits – such as low chlolesterol and lower blood pressure.”
The downside is that while low IGF-1 appears to improve your chances of health ageing, it may also have a drastic effect on your ability to reproduce, especially for females. Genetic experiments in fruit flies in which IGF-1 production is knocked out altogether result in a big increase in lifespan, but also render the insects infertile.
This could prove to be a defining conundrum for future generations of humans. Our natural instinct is not only to reproduce but also prolong our survival for as long as possible, but can we have both?
Researchers from the Institute of Experimental Genetics in Germany and the National Research Centre for Growth and Development in New Zealand, have been looking at ways of manipulating the cascade of processes controlled by IGF-1 –without the need for extreme calorie restriction. One method involves a substance called resveratrol, which is found in red wine and affects energy metabolism. However, just as was predicted by Tom Kirkwood 40 years ago, the evidence suggests that such tinkering leads to a trade-off between longevity and reproduction, reducing fertility.
If it came to it, which would you choose?