For centuries, humans have searched for ways to extend life. Alchemists never found the philosopher’s stone, but scientists have consistently shown that a longer life can be attained by eating less – at least in certain lab animals. But can we find a way to live longer while still enjoying our food?
Compounds that mimic the biological effects of dieting could be the answer, and the two most popular diet-mimicking drugs are rapamycin and metformin. In a new study, my colleagues and I found that rapamycin prolongs life almost as consistently as eating less, whereas metformin does not.
Mimicking calorie restrictions
Eating less, or dietary restriction, has been the gold standard for achieving a longer life ever since a study nearly a century ago in which laboratory rats that ate less surprised scientists by outliving their well-fed lab mates.
But for many people, sticking to a permanent diet is hard and far from enjoyable. Also, if taken to extremes, it can even be bad for health. That is why we wanted to know whether drugs that are dieting mimics could bring the same benefit of eating less without the unwanted side-effects.
Rapamycin was first discovered in bacteria living in Easter Island soil in the 1970s, and medical professionals now use it to prevent organ-transplant rejection, as it is a powerful immunosuppressant. It works by blocking a molecular switch that tells cells when nutrients are abundant.
Metformin, meanwhile, is a synthetic descendant of a compound found in French lilac (also known as goat’s rue) and is widely prescribed to control blood sugar in type 2 diabetes. Both drugs are involved in the body’s ability to sense nutrients and energy, so biologists like us hoped they might copy the mechanisms activated by eating less.
To find out, we pooled the results of many studies to see if there were any overall patterns. We carefully examined thousands of scientific papers to finally home in on 167 studies on eight vertebrate species, from fish to monkeys, that provided sufficient details on survival and how the study was done. Then we compared three longevity strategies: eating less, taking rapamycin and taking metformin.
We found that eating less still came out on top as the most consistent way to prolong life in all animals but rapamycin was close behind. Metformin, in contrast, showed no clear benefit. The life-extension effect of eating less was the same in both sexes, and it didn’t matter whether the diet plan involved eating smaller portions or intermittent fasting.
That makes rapamycin one of the most exciting leads for new anti-ageing therapies. Ageing might not be considered a disease, but it is a risk factor behind many diseases from cancer to dementia. If we slow that underlying process, the benefit will be extra years of quality life and lower healthcare bills as the world’s population grows older.
Encouraging early signs, but we’re not quite there yet
However, there are some important points to consider. First, we discovered considerable variation from experiment to experiment with some studies even showing that eating less or taking rapamycin reduced lifespan.
Also, most of the evidence originates from mice and rats that have many of our genes but are clearly not exactly like us.
Finally, rapamycin may have side-effects such as repressing immunity and reproduction. Researchers are now investigating milder doses of rapamycin to see if they provide the advantages without the side-effects.
The preliminary signs are encouraging. In an ongoing human rapamycin trial, volunteers given low, intermittent doses of rapamycin have experienced positive effects on indicators of healthspan. For metformin, the human trial is still in progress and the findings are expected to be out in a few years time.
For now, nobody should run to their doctor asking for prescriptions of rapamycin to live longer. But this drug, extracted from obscure soil bacteria, shows us that interfering with a single molecular pathway can be enough to mimic the benefits of eating less. The challenge is to use this discovery to produce therapies that make us healthier for longer without compromising our quality of life – or our taste for the occasional slice of chocolate cake.
Zahida Sultanova, Post Doctoral Research Fellow, School of Biological Sciences, University of East Anglia
This article is republished from The Conversation under a Creative Commons license. Read the original article.
