Eat Less, Live Longer
An article in New Scientist shines light on research finding that radically reducing intake of food, especially protein, can lead to a longer, healthier life.
Calorie restriction dramatically extends not only the lifespan of laboratory animals, but also their “healthspan” – how long they live free of disease. On the assumption that it has the same effect in people, some individuals have already adopted a restricted diet. The latest evidence suggests that while calorie restriction is indeed beneficial for humans, when it comes to lifespan extension, it may not be the whole story.
Calorie restriction has since been shown to extend the lives of other organisms including yeast, nematode worms, fruit flies and mice. Mice, for example, live up to 50 per cent longer if their calorie intake is cut by 30 to 50 per cent. What’s more, mammals are protected from a number of age-associated maladies such as cancer, heart disease, type 2 diabetes and Alzheimer’s disease.
It is unclear why eating less should make animals live longer. While a restricted diet triggers numerous changes at the molecular and genetic levels, only some of these are common across all the species tested. However, there does seem to be a general principle that a dearth of nutrients causes organisms to divert resources away from growth and reproduction and towards basic survival functions. From an evolutionary perspective, these adaptations could help an organism survive famine.
Needless to say, this lifestyle is not for everyone. Some people report struggling with hunger pangs, and the society warns on its website that side effects can include feeling cold, poor wound-healing and temporary infertility.
But Fontana has found a notable difference in the way people and animals respond to calorie restriction, and it is not great news. It involves a hormone made by the liver called insulin-like growth factor 1.
IGF-1 has emerged as an important promoter of ageing. IGF-1 levels are lower than normal in worms, flies and mice on a restricted diet, and this is thought to be at least partly responsible for their longer lifespan. When it comes to people, however, CRONies have the same IGF-1 levels as the rest of us.
If the new theory is right, then the whole concept of calorie restriction needs to be rethought. The very term would be misleading; Fontana and others have started referring to dietary restriction instead. As news of the study has spread, some CRONies have already reduced their protein intake.
The protein theory is bad news for people on low-carbohydrate weight-loss plans like the Atkins diet. “I’d be wary of diets that put a heavy emphasis on protein,” says Piper. “It’s hard to see how that could be healthy.” Fontana goes one step further, saying that high-protein diets could risk accelerated ageing and cancer.
It’s good news, however, for people already on low-protein diets, like vegans, who avoid eating meat, eggs and dairy products.
My initial thoughts on this is that, if this is what it takes to live a longer life, I don’t want it. That is, while health and longevity have utility in and of themselves, so does pleasure. Who wants to live a long life of deprivation and hunger?
Further, healthy people can get hit by a bus. So even living a miserable existence doesn’t guarantee that you’ll live a long time even if you decide the trade-off is worth it.
Thankfully, scientists have realized that most people aren’t going to live this extreme lifestyle.
For those who don’t fancy changing their diet, a more tempting prospect is a pill that replicates the effects without the hard work. Drug firms have taken a keen interest in trying to find such calorie-restriction mimetics, as they are sometimes called.
A decade ago the main focus was on signalling molecules called sirtuins that reduce the expression of several ageing-related genes. Reports that resveratrol, a compound found in red wine, extended lifespan in some species by activating sirtuins boosted sales of red wine and resveratrol supplements. Resveratrol still has supporters, but inconsistent animal data have since dampened much of the enthusiasm.
The focus has lately switched to finding compounds that block TOR. One such agent is a drug called rapamycin, an immunosuppressant given to recipients of organ transplants. Last year rapamycin was found to extend the lifespan of mice, even in those started on the drug in later life, equivalent to 60-year-old humans (Nature, vol 460, p 392). However, because people don’t live in a sanitised lab environment, rapamycin’s strong immunosuppressive effects make it an unlikely candidate for a practical anti-ageing drug. Similar compounds that are less toxic would be more promising.
Another candidate is a drug called metformin, already used to treat type 2 diabetes. Metformin also blocks TOR, and lengthens lifespan in worms and mice (Cell Metabolism, vol 11, p 390). Does metformin slow ageing in people too? Studies published earlier this year suggest that diabetics taking metformin do get less cancer (Diabetes Care, vol 33, p 322). “The major risk factor for cancer, above all others, is ageing,” says David Gems at University College London. He calls the studies a “smoking gun of a more generalised effect of metformin on ageing, rather than just strictly diabetes”.
While metformin is less toxic than rapamycin, it, too, can have side effects, such as nausea and diarrhoea. So researchers may have a way to go before they find the perfect longevity pill.
Now that’s more like it! Americans love pharmaceutical solutions.