This popular science piece covers some of the high points of recent years in the field of calorie restriction research. It is above average for the type, though it has to be said that the bar has been set low by the media in recent years. This long-standing area of research involves quantifying the benefits to health and longevity produced by consuming fewer calories while still obtaining an optimal level of micronutrients, mapping the cellular mechanisms involved, and a search for ways to recreate some of these effects via calorie restriction mimetic drugs rather than diet.
Thanks to advances in medicine and improvements in healthy living, we benefiting from longer lifespans and also experiencing longer “healthspans”. So, what do we need to do to enhance the length and quality of our lives even more? Researchers worldwide are pursuing various ideas, but for some researchers, the answer is a simple change in diet. They believe that the key to a better old age may be to reduce the amount of food on our plates, via an approach called “calorie restriction”. This diet goes further than cutting back on fatty foods from time-to-time; it’s about making gradual and careful reductions in portion size permanently.
Since a foundational study in 1935 in white rats, a dietary restriction of between 30-50% has been shown to extend lifespan, delaying death from age-related disorders and disease. Of course, what works for a rat or any other laboratory organism might not work for a human. Long-term trials, following humans from early adulthood to death, are a rarity. “I don’t see a human study of longevity as something that would be a fundable research programme. Even if you start humans at 40 or 50 years old, you’re still looking at potentially 40 or 50 more years of study.” That’s why, in the late 1980s, two independent long-term trials – one at NIA and the other at the University of Wisconsin – were set up to study calorie restriction and ageing in Rhesus monkeys. Not only do we share 93% of our DNA with these primates, we age in the same way too.
They are far from malnourished or starving. Take Sherman, a 43-year-old monkey from NIA. Since being placed on the CR diet in 1987, aged 16, Sherman hasn’t shown any overt signs of hunger that are well characterised in his species. Sherman is the oldest Rhesus monkey ever recorded, nearly 20 years older than the average lifespan for his species in captivity. Even into his 30s he would have been considered an old monkey, but he didn’t look or act like one. The same is true, to varying extents, for the rest of his experimental troop at NIA. “We have demonstrated that ageing can be manipulated in primates. It kind of gets glossed over because it’s obvious, but conceptually that’s hugely important; it means that ageing itself is a reasonable target for clinical intervention and medical treatment.”
If ageing can be delayed, in other words, all of the diseases associated with it will follow suit. “Going after each disease one at a time isn’t going to significantly extend lifespan for people because they’ll die of something else. If you cured all cancers, you wouldn’t offset death due to cardiovascular disease, or dementia, or diabetes-associated disorders. Whereas if you go after ageing you can offset the lot in one go.”
In the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy trial, also known as Calerie, over two years, 218 healthy men and women aged between 21 and 50 years were split into two groups. In one, people were allowed to eat as they normally would (ad libitum), while the other ate 25% less (CR). Both had health checks every six months. Unlike in the Rhesus monkey trials, tests over two years can’t determine whether CR reduces or delays age-related diseases. There simply isn’t enough time for their development. But the Calerie trials tested for the next best thing: the early biological signs of heart disease, cancer, and diabetes. The results after two years were very positive. In the blood of calorie-restricted people, the ratio of “good” cholesterol to “bad” cholesterol had increased, molecules associated with tumour formation – called tumour necrosis factors (TNFs) – were reduced by around 25%, and levels of insulin resistance, a sure sign of diabetes, fell by nearly 40% compared to people who ate their normal diets. Overall, blood pressure was lower.
With less food, is the metabolism forced to be more efficient with what it has? Is there a common molecular switch regulating ageing that is turned on (or off) with fewer calories? Or is there an as of yet unknown mechanism underpinning our lives and deaths? Answers to such questions might be long in coming. “If I cloned 10 of myself and we all worked furiously, I don’t think we’d have it solved. The biology is inordinately complicated.” It’s a worthwhile undertaking – understand how CR works and other treatments could then be used to target that specific part of our biology. Ageing could be treated directly, that is, without the need of calorie restriction.