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Calorie Restriction for Life Extension: What Are the Alternatives?

Eating disorder

It’s been known for a while that 20-40% calorie restriction is a pretty great way to extend the lifespan of experimental animals. On the other hand, no studies have directly tested this in humans, and some studies like this one make the case that the animal results probably aren’t generalizable.

But more importantly, even if life-long calorie restriction did work in humans who in their right mind would want to do that? It might be tolerable during weight loss, but in people who don’t have any weight to lose, that level of calorie restriction is miserable. You’d have to be hungry all the time for the rest of your life. And at the level required to extend lifespan, calorie restriction causes a major drop in body temperature and metabolic rate. Physical performance and reproductive health also get compromised – it’s just very unpleasant, and most people won’t do it.

Enter calorie restriction mimetics. A calorie restriction mimetic is anything that imitates the effects of calorie restriction without requiring any reduction in calories. The idea is to figure out how calorie restriction works (which genes it turns on or off, which hormones it influences, which cellular processes it speeds up or slows down, etc.) and then find another way to do that.

Is Calorie Restriction Necessary?

As this review explains, one prominent theory is that calorie restriction works by turning on the stress response. The stress of chronic calorie restriction provokes a resource shift from performance to maintenance. Basically, your body recognizes a physical challenge (not enough food coming in) and starts working harder to keep you alive. This turns up cellular repair and other processes that combat aging (If you’re familiar with the concept of hormetic stress, this is a great example).

In this model, a calorie deficit is the key. But there’s one big challenge to that view: creating a calorie deficit via exercise doesn’t work. If all you need is a calorie deficit, then exercise should work as well as restricting food. So clearly, there’s something more going on than just the pure calorie deficit.

Nobody can quite agree on what that is, and there’s almost certainly more than one thing going on here. But based on the different theories about how calorie restriction works, here are four diet-based strategies that might be good calorie restriction mimetics. All four are completely compatible with Paleo. In fact, if you’re eating Paleo, you might be doing some of them already!

Paleo-Friendly Calorie Restriction Mimetics

Resveratrol (for sirtuin gene activation)Red wine

Calorie restriction activates sirtuin genes, and some theories hold that the sirtuin gene activation is critical to the benefits of the restriction. As this review explains:

“Sirtuin proteins bolster stress resistance of mammalian cells by virtue of their ability to remodel metabolism, alter inflammatory responses, and enhance the ability to cope with oxidative species. Because many of these same pathways are pathologically altered in the aged, activation of sirtuins represents a feasible means for attenuating age-related decline in physiological function.

One alternative strategy for activating sirtuin genes might be resveratrol, the antioxidant found in red wine (and to a lesser extent, grapes and other grape products). This study found that 150 mg of resveratrol per day increased sirtuin gene expression and also had a bunch of other benefits associated with calorie restriction. In 11 obese men, resveratrol improved mitochondrial function, insulin sensitivity, blood lipids, blood pressure, and blood sugar regulation – not bad!

Unfortunately, it’s not possible to get this amount of resveratrol from diet. This study saw benefits from a lower dose, but in mice, so take it with a grain of salt. On the other hand, it’s hard to think of who would be hurt by eating some delicious grapes or raisins, or even a glass of red wine if that fits well with your body.

Occasional Fasting (to Reduce Stress from Digestive Processes)

One explanation for the benefits of food reduction over exercise is that digestion itself is difficult and stressful. Simply taking occasional breaks from digestion might be valuable – this would explain why restricting dietary calories works, but creating the same calorie deficit via exercise doesn’t.

Considering this, occasional fasting without chronic calorie restriction might be a good choice for some people. Fasting upregulates cellular repair and imitates several of the effects of calorie restriction. In fact, as this review puts it, “the life-extending benefits of ADF [alternate-day fasting] may rival those of CR [calorie restriction]”

Some different ways of fasting:

Ketogenic Diets (to inhibit mTOR signaling)

As this review explains:

“Following calorie restriction or consumption of a ketogenic diet, there is notable improvement in mitochondrial function, a decrease in the expression of apoptotic and inflammatory mediators and an increase in the activity of neurotrophic factors….Recent research aimed at identifying compounds that can reproduce, at least partially, the neuroprotective effects of [calorie-restricted] diets with less demanding changes to food intake suggests that ketone bodies might represent an appropriate candidate”

Ketogenic diets might work by inhibiting the mTOR signaling pathway, which regulates a bunch of different cellular processes. Calorie restriction also inhibits mTOR signaling, and this is another mechanism that’s been proposed to explain its benefits. Because ketogenic diets also inhibit mTOR signalling, they might be calorie restriction mimetics in that sense.

Ketosis might also be helpful because ketone bodies themselves mimic calorie restriction and cause specific anti-aging changes through a completely separate mechanism.

Keto isn’t for everyone, but if it works for you, there might be even more benefits than you knew about.

Low-Methionine Diets (Organ Meats!)

Methionine is an amino acid. Another theory about calorie restriction is that the benefits actually come from methionine restriction. Take this review:

Fresh liver

Eat more of the odd bits: they’re good for you!

“approximately half of the life extension effect of CR seems to be ascribable to protein restriction. A wealth of evidence indicates that methionine restriction might account for most or all of the life-extending benefits of protein restriction.”

The benefits of methionine restriction might also explain why a ketogenic diet can work as a calorie restriction mimetic: keto is low-protein, so it’s low-methionine by default.

Protein is generally good for you, so a low-protein diet probably won’t be optimal for most people. But one simple strategy to get the benefits of methionine reduction is to eat more organ meats. Organ meats are low in methionine and also provide more of the protein glycine, which can balance out methionine from other sources. There’s a reason why so many traditional food cultures include organ meats in their cuisine – they really do offer a lot of health benefits.

Summing it Up

The obligatory killjoy disclaimer here: there’s no such thing as a diet that guarantees immortality or even a longer life. None of the things listed above are magical silver bullets that prevent aging. On the other hand, looking at that list, it starts to look like Paleo is a pretty great anti-aging diet:

It’s true that none of these things have been directly tested for life extension in human subjects any more than calorie restriction has. But the mimetics are a lot less extreme than chronic calorie restriction, and they’re healthful for other reasons anyway. There’s a similar level of evidence for these calorie restriction mimetics, but there’s much less guaranteed pain and suffering – for most people who want to enjoy their potential life extension, the less extreme strategies seem like they’d be preferable.