A time-honored and research-tested way to extend an animal’s lifespan is to restrict its caloric intake. Studies repeatedly confirm that if, say, a lab mouse normally gets two full bowls of lab chow a day, limiting that mouse to one and a half bowls of lab chow a day will make that mouse live longer than the mouse eating the full two bowls. Cool, cool, a longer life is great and all, but what about the downsides of straight calorie restriction, aside from willfully restricting your food intake, ignoring hunger pangs, relegating yourself to feeling discontent with meals, and counting calories and macronutrients obsessively? Are there any others? Sure:
Loss of muscle mass. Humans undergoing calorie restriction often suffer loss of lean muscle mass and strength , all pretty objectively negative effects (unless you really go for the gaunt “Christian Bale in The Machinist ” look and use a super-strong bionic exoskeleton for all your physical tasks).
Loss of bone mineral density. Humans who calorie restrict in studies also show signs of lower bone mineral density when compared to humans who lose weight from exercise, particularly in the hip and spine  – the two areas most susceptible to fall-related bone breaks. I wrote about this study some time ago here .
Oh, and there’s the fact that the act of restricting one’s calories can be mind-numbing, miserable, and difficult for a great many people, especially if it’s a lifelong pursuit. (Unless, of course, you eat according to the Primal Blueprint  and are fat-adapted . It can make CR not only tolerable, but a cinch because we become so good at living off stored body fat. We don’t suffer from sugar lows when we skip meals  the way most people who fast do, but I digress.) That’s kind of a biggie.
What about fasting? In previous installments  of this series, I’ve explained how fasting can sometimes be described as a “short cut” to the benefits of calorie restriction , an easier (and even more effective) path to the same destination. Studies on fasting/calorie restriction and cancer  find that fasting is more effective in a shorter amount of time (weeks or months versus mere days). Does the same hold true for longevity? Can fasting also extend lifespan without making us look like a calorie-restricted monkey ?
1945 marks the first real study (PDF ) of the effects of intermittent fasting  on lifespan in animals. Beginning at day 42 of their lives, rats were either fasted one day in four, one day in three, or every other day. All fasted rats, save for the females who were fasted one day in four, lived longer than control rats on a normal schedule. Although females outlived males in general (like always), fasting had the greatest effect in males. Male rats did best on every other day fasting; female rats did best on one day in three fasting. Fasted rats weighed less than control rats, so they likely also ate less, even though feeding days were ad libitum.
In a 1982 study, mice fed every other day lived 82% longer than mice fed ad libitum every day . No word on calorie intake.
Another study  from 1983 showed that rats fed every other day lived longer and had lower body weights than rats fed daily and ad libitum. Fasted rats were less active in their youth, but more active than control rats when adults. The lower body weights in the fasted rats indicate a reduced calorie intake.
In 2000, female mice who fasted for four consecutive days every two weeks lived for 64 weeks on average , while normal fed mice lived just 47 weeks. Interestingly, the fasted mice were heavier than the fed mice throughout the experiment, which indicates that calories weren’t significantly restricted.
Okay, so it looks like fasting promotes longevity, which may be mediated by a reduction in calories. Provided the faster doesn’t gorge him or herself on the feeding days so much that they make up for all the missing calories, it should be effective. In other words, fasting promotes longevity in all but the most ardent of big eaters. I don’t see this as a “gotcha” or a problem, because fasting almost invariably produces calorie restriction. (I might eat a fairly big meal after a long fast, but I definitely have never doubled my intake to make up for the fasted day.) In fact, that fasting makes calorie reduction painless and inadvertent is a highly-touted feature of the practice, and a big part as to why it’s so effective for people who have failed with traditional calorie restriction.
So, how’s it all work? Is it just the calorie restriction?
Perhaps. One potential pathway by which both fasting and CR increase lifespan is via inhibition of mammalian target of rapamycin, or mTOR. The mTOR pathway can be said to drive the aging process . It is necessary for cell growth, like muscle cells  (in stable mTOR states) or certain cancer cells  (in overactive mTOR states), and it is highly sensitive to nutrient availability and hormonal signaling. In mice, feeding rapamycin – a potent inhibitor of mTOR – increases lifespan . Both not eating (fasting) and lowering potential hormonal messengers (like insulin ) also inhibit mTOR activity  by spiking AMPK . Indeed, in the presence of insulin, mTOR is upregulated. We know from previous posts that fasting reduces fasting insulin. In insulin resistant people, insulin is chronically elevated and mTOR is overactive. We also know that fasting reduces insulin resistance  and increases insulin sensitivity, thus normalizing or inhibiting excessive mTOR activity. This kind of mTOR inhibition also works with CR, but if adherence is easier, side effects are lessened, and AMPK spiking is greater with total caloric restriction (fasting) than with partial CR, which is the more effective method?
So, it’s starting to look like the longevity benefits of fasting can be attributed to the degree of caloric restriction. That is, fasting is total caloric restriction, while CR is partial. When you fast, you’re going whole hog. You’re subjecting yourself to an acute stressor, getting the hormetic benefits, and then recovering from that stressor  by eating normally thereafter (until you do it again). When you calorie restrict, you’re undergoing a chronic stressor. Day in, day out, you’re worrying about food, restricting energy and nutrient intake, and there’s really no period of recovery. You’re always residing in a partially restricted state, drifting from paltry meal to paltry meal. There is no feast . It’s like lifting heavy and sprinting a few times a week versus jogging a 10k every day. Chronic cardio  versus acute, high intensity exercise.
What about “healthspan”? Can fasting compress morbidity  – can it help us in our quest to live long and drop dead ? I mean, let’s face it: who wants to be a frail, skinny-fat centenarian relegated to the bed or the walker or the wheelchair?
Well, we know that intermittent fasting appears to conserve more lean mass than CR. In a recent meta-analysis , one group of researchers directly compared studies on calorie restriction to studies on intermittent fasting and found that while both were good for losing weight, “intermittent CR may be more effective for the retention of lean mass.” And at the very least, I’d suggest to you that having better insulin sensitivity, less fat mass, more lean mass , a better-regulated mTOR pathway, improved blood lipids , better glucose control, and a less restricted diet makes for a better healthspan, a more enjoyable life, and a reduced risk of dying from the diseases of civilization.
Bottom line: fasting may not work by some magical pathway separate from caloric restriction. It may, but it hasn’t been established. What we do know is that fasting (whether by inadvertent, enhanced calorie restriction or whatever else) improves lifespan in lab mammals and improves various health markers associated with aging and longevity in both humans and animals. Fasting may not give you an immediate “Life + 25″ boost, and there haven’t been any real lifespan and fasting studies done on humans (if only we had mice-like lifespans!), but if it makes you less likely to get obese, diabetes, heart disease, or cancer, you’re less likely to die from those things. The fewer things you have trying to kill you, the longer you generally live.
That’s it for today, folks. Thanks for reading. Any questions? Comments?
Here’s the entire series for easy reference: