We can call it a vale of tears till the cows come home but the fact is, most of us aspire to die old, if at all. Vast effort is going into aging in hope of staving off the evil day. Therefore, studies suggesting a longer life in abstemious animals (albeit ones held in captivity who were simply fed less) were hailed. But why actually they lived longer remained unclear.
Now, a new study has delved deeper and found that we – the mice among us, at least – can’t just eat all day as long as the calorie count is less than usual, and live longer. No, we can’t.
The parameter crucial to longevity involved not calorie restriction per se – that on its own achieved nothing. The crucial parameter was prolonged fasting each and every day, according to new research published Monday in Nature by Heidi Pak of the University of Wisconsin-Madison and colleagues.
Put clearly: Fasting every day – from the one meal a day to the same the next day – was enough to achieve the geroprotective effect, co-author Dudley Lamming, also of University of Wisconsin-Madison, confirmed to Haaretz. In mice, we repeat, in mice.
This is good to know, if we want to stay in the vale, because free-range humans find it difficult to adhere to reduced-calorie regimes over time. We don’t just fall off the wagon, we roll off.
So, if fasting is the key and not the calorie restriction, could a mouse be fed with mouse candy once a day, fast the rest and still achieve the greater longevity? They didn’t test for that, Lamming explains: “We only tested ‘feasting’ with a normal diet, didn’t test what happens if the short ‘feasting’ period mice eat a very unhealthy/fattening/candy-like/American diet. Based on the literature about calorie restriction, I would guess that you would still have some positive effects, but probably not all of them.”
The mouse diet
No such calorie restriction/longevity research has been conducted on humans, for whom the parameters are more difficult to control. Also, we tend to lie. But one may surmise that if daily fasting promotes healthy aging in mice, rats, dogs, fish and non-human primates, it may well apply to humans too.
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Given how much work has been done, how had the role of fasting itself not been noticed during previous work on calorie restriction? Because until now, researchers studying calorie restriction in caged rodents routinely, unthinkingly fed the animals only once a day. The rodents eat the lot in a couple of hours and then get nothing for the rest of the day, i.e., around 22 hours a day, the team explains.
The experiments indeed indicated that calorie restriction was geroprotective (at least up to a point: there’s that revolting parable about a miser who fed his horse less and less every day until suddenly it died just at the point, the man groused, he had accustomed it to a grain of rice a day).
So having noticed that, de facto, lab rodents fast for most of the day, the researchers wondered if that, and not the diet per se, was the factor. The new study put the rodents though a series of feeding regimens, to test whether fasting is required at all and whether calorie restriction is required at all.
How was the murine longevity measured exactly? Did they impose the regimes, then sit and wait for the mice to die? That too. “We measured their lifespan and, as they aged, we examined metabolic health, frailty and memory, which are proxies of aging,” Lamming explains. We add that the lab mice live on average for about two years.
Since different strains of mice evince somewhat different responses to dieting, they used two specific inbred strains. “All the individuals of inbred mice are genetically identical – and thus there is some potential that results from looking at just one strain of mice might not apply as well to the human population,” Lamming says, explaining that choice.
“We show that fasting seems to be generally required for the benefits of calorie restriction in two different strains of mice, increasing confidence that these results might apply more broadly to the human population,” he adds.
Conclusion: Eating once a day and fasting for the rest of it is how a mouse may achieve the desired lifespan supposedly conferred by a calorie-restricted diet. They checked for differences between males and females, and didn’t find anything much.
And with that the team has debunked the long-held belief that if you half-starve your monkey and your mouse, you improve their chances of living longer. It isn’t just the reduced caloric intake; it’s the fasting between the once-a-day meal.
Why would it make evolutionary sense for protracted daily fasting to improve our physiological responses? Theories about calorie restriction per se abound, Lamming says.
“For example, if calories are low during a drought or something, you might not want to have babies since you might not be able to feed them – so instead it would make sense to invest in repairing your body so you can live to have babies when food returns,” he says. “As for fasting, it seems like our bodies and mice like to have a period of time during the day when it is not metabolizing food, possibly linked to circadian rhythm and the light/dark cycle.”
Imagine what we have saved you with this story – though again, we stress the effect has not been demonstrated to humans: In theory, you do not have to spend your days eating unpalatable low-calorie seaweed; you can eat normal food – but probably not absolute garbage – for a couple of hours a day and abstemiousness the rest of the day will do it. About candy, the jury’s still out.
Thinking about being able to eat for say two hours a day and not eating for the rest of it, one wonders if the calorie-restricted mice are crankier than normal mice. “Hangry” is a thing, in humanity at least.
“We didn’t really assess here, but it is well-known that calorie-restricted mice usually move more, particularly when they are expecting to be fed,” Lamming answers, adding that it’s hard to say if a mouse is cranky but they don’t seem particularly irritable. It may not work the same way with humans.