Two 27-year-old male rhesus monkeys, one on a calorie-restricted diet (left) and the other untreated. Photo: National
The science of calorie restriction just got a lot more complicated.
Rhesus monkeys fed experimental low-calorie diets didn’t live any longer than their high-calorie brethren, a result that conflicts with a 2009 report of long-lived, extra-low-calorie monkeys.
That had been the first demonstration of extended lifespans in primates, not just lab rodents, and raised hopes of the diet being a dinner-plate fountain of youth. The new findings seem to challenge that notion, though they’re far from conclusive.
More fundamentally, the findings pop the lid on a roiling scientific back-and-forth over calorie restriction’s effects and mechanisms, a matter of vigorous contention that’s belied by popular notions of the diet as a simple, straightforward longevity hack.
“From the beginning, there have been people who were true believers in the effects of calorie restriction in every single species,” said Rafa de Cabo, a National Institute on Aging gerontologist and co-author of the new study, published Aug. 29 in Nature. “Often attention wasn’t paid to data showing that in some cases calorie restriction wasn’t good, or didn’t produce the effects it should have.”
De Cabo’s experiment started in 1987, right around the time as another, similar experiment at the University of Wisconsin. Both groups wanted to know whether calorie restriction — cutting intake by up to 40 percent below what’s typically considered healthy — would have the same health-protecting, life-prolonging effects in primates that it seemed to have in lab animals.
In 2009, the Wisconsin group reported that CR, as the diet is known, indeed extended their monkeys’ lifespans. But in the new study, researchers led by de Cabo and fellow NIA gerontologist Julie Mattison report no extension, at least in monkeys who started CR in middle age or late in their lives. (Monkeys who started during infancy aren’t yet old, so their longevity results won’t be known for another decade or so.)
De Cabo and Mattison’s CR monkeys, 57 in total, have shown signs of better health, though they’re mixed. For example, males have low cholesterol and blood sugar, but not females. And even across-the-board health improvements would be underwhelming in comparison to calorie restriction’s sometimes overwhelming expectations.
“What some people were hoping is that CR would extend longevity beyond the normal, that with a good CR diet you would live for 120 years,” said gerontologist Steven Austad of the University of Texas, who was not involved in the study. “I think these studies show together that diet is not, no matter how you do it, going to get people living to 120.”
Austad’s own work found that CR didn’t work on descendants of mice recently caught in the wild, rather than bred from lab-adapted mice that may be so unnatural and intrinsically unhealthy as to give misleading results.
Those findings fit with anecdotal stories Austad heard from researchers who, having found no positive effects of CR in their experiments, didn’t report the results because they assumed they’d made mistakes. Other accounts described calorie restrictionhaving very different effects in different strains of mice.
Depending on their genetic makeup, some mice lived longer, but some died sooner. In others there was no change. And there were also reports that feeding strategies, diet composition and even housing affected CR’s outcomes. All those nuances are recapitulated in the monkey studies.
In the Wisconsin experiment, for example, control-group monkeys were allowed to eat whenever they wanted, with food dishes kept perpetually full, and their diet was high in sugar. Compared to them, calorie-restricted monkeys seemed longer-lived, but even a moderate diet might have achieved similar results.
In the NIA experiment, the control monkeys ate a fairly healthy, low-sugar diet. Perhaps calorie restriction just couldn’t improve it much — but it could also be argued, said Austad, that the controls were still overweight compared to wild monkeys. In that case, what the researchers called calorie restriction wasn’ttrue restriction, which would need to be even more extreme.
The Wisconsin results might also have been skewed by the researchers eliminating from their statistical analyses monkeys who died from non-disease-related causes, such as complications during anesthesia. With those monkeys included, apparent longevity increases would dwindle.
Even though some health improvements, such as lower rates of cancer and metabolic diseases, were seen in the NIA monkeys, this might just validate common sense, said Austad. “Even in the best CR scenario, you may not get any health benefits you wouldn’t get from maintaining what everyone knows is a healthy body weight,” he said. “If I told you that if you’re overweight and you lose weight, you’ll get health benefits, you’ll say, ‘Tell me something I don’t know.’”
According to Luigi Fontana, a gerontologist at Washington University, who studies CR in people who are experimenting with the diet, neither of the monkey studies is entirely reliable.
One potentially confounding effect is stress. To ensure regular, closely monitored feeding, monkeys in both studies were kept in isolated cages. (The photograph above was taken for illustrative purposes, and doesn’t represent day-to-day conditions.) For monkeys, that’s hardly a salutary environment.
“If you’re in a single cage for your whole life, and are a highly intelligent animal like a primate, deprived of contact with other peers, and on top of that you’re calorically restricted — can you imagine the psychological depression issues that will ensue?” said Fontana. “And we know the hypothalamus in the brain is a major regulator of many downstream metabolic factors.”
Fontana pointed out that key hormonal changes found in both calorie-restricted mice and humans were not detected in either group of monkeys, an absence that he blames on their relatively high-protein diets.
In humans, those hormones decrease only when protein intake is dramatically reduced. It’s not enough to cut calories alone. “It’s possible that we don’t see some of the beneficial effects of longevity in these monkeys because they were on a high-protein diet,” Fontana said.
“The old idea is that a calorie is a calorie. When you restrict it, you have a beneficial effect. Our data and other data suggests this isn’t the case. The quality of the diet matters,” Fontana continued.
The NIA and Wisconsin teams are currently studying the differences between their results. “Any interpretation of the data is feasible. Any hypothesis that emerges from these observations should be tested. This is not the final word,” said de Cabo. “There are a lot of things we need to understand.”
“It’s not that one group did right and the other group wrong. They all did a fine job with the experiments. This just shows that fine details matter,” said Austad. “People shouldn’t say, ‘Let’s drop CR.’ They should say, ‘Let’s figure it out.’”
“There’s no doubt that calorie restriction has a tremendous impact on the onset and progression of diseases. That’s a consistent observation, regardless of animal species. The effect on survival is a completely different story. We’re now trying to tease out the difference between healthspan and lifespan,” said de Cabo.
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volcabularies:
1. brethren n. pl. (複數 plural) 1. 同胞,同黨,同業 有時也用 brothers
2. vigorous adj. 1. 精力旺盛的,充滿生氣的,有活力的,活潑的
3. belie vt. 1. 顯示…是假的,與…抵觸 2. 掩飾,使人對…誤解 3. 違背(諾言),辜負(期望),使…失望 4. 就…扯謊;中傷
4. anecdotal adj. 1. 軼聞(風格)的;軼事多的
5. recapitulate vt. vi. 1. 扼要重述,概述
6. anesthesia n. 1. 感覺缺失
7. salutary adj. 1. 有益的,有利的
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Q1: Do you agree that low calorie diet acturally help long lifespan? what's your argument?
Q2: Are u a fan of food? what kinds of food do you like mostly?
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