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Caloric Restriction, Red Wine, and Aging

First, a summary:

  • The physiological stress resulting from caloric restriction may extend your life. It could accomplish this by switching resources from reproduction to self-preservation. Alternatively (or additionally), it might accomplish this by helping downregulate insulin, thereby reducing the diseases associated with metabolic syndrome.
  • Resveratrol (Via red wine, for now) might also slow aging via some SIRT-1 mechanism or by somehow signaling to the body that stressful times lay ahead.
  • The stress from exercise3 might slow aging by activating physiological mechanisms of tissue self-preservation, as well.
  • And finally, I can chalk another one up for intermittent fasting, which personal experience says is the easiest way to practice caloric restriction.

The Details

My brother sent me a NYTimes article that talks about resveratrol, a molecule found in red wine, and its possible link to slowing aging. Resveratrol may thwart aging by spurring the production of sirtuins a.k.a. SIRT1 in humans. Per the Times:

[T]he door has now been opened to drugs that exploit an ancient biological survival mechanism, that of switching the body’s resources from fertility to tissue maintenance. The improved tissue maintenance seems to extend life by cutting down on the degenerative diseases of aging.

The reflex can be prompted by a faminelike diet, known as caloric restriction, which extends the life of laboratory rodents by up to 30 percent but is far too hard for most people to keep to and in any case has not been proven to work in humans [See Footnote 1 for discussion on this last sentence].

Whereas the Times article focuses on resveratrol, summarily dismissing caloric restriction, a 2006 article from The Economist does the opposite, going into more detail on the impact of caloric restriction on human aging and a recent study on the matter:

[E]vidence has been accumulating since the 1930s that calorie restriction … extends lifespan and delays the onset of age-related diseases in rats, dogs, fish and monkeys. …

Amid the hype, it is easy to forget that no one has until now shown that calorie restriction works in humans. That omission, however, changed this month, with the publication of the initial results of the first systematic investigation into the matter. This study, known as CALERIE2 (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), was sponsored by America’s National Institutes of Health. …

CALERIE suggests the [advantages of caloric restriction] are real. For example, those on restricted diets had lower insulin resistance … and lower levels of low-density lipoprotein [LDL] cholesterol. They showed drops in body temperature and blood-insulin levels?both phenomena that have been seen in long-lived, calorie-restricted animals. They also suffered less oxidative damage to their DNA.

The Economist article goes on to talk about resveratrol and even exercise:

Resveratrol is produced when a vine is under stress?for example, due to dehydration or over-exposure to sunshine. According to Dr Sinclair’s theory, which he calls xenohormesis, animals rely on such botanical stress signals to give them extra information about their own environments, in the same way that the alarm calls of one species warn others of danger. If bad things are happening to plants, he surmises, that is a reason for pre-emptive animal action. Animal bodies thus react to molecules such as resveratrol by activating their own defence mechanisms. These, in turn, protect their cells from stress-related damage.

Xenohormesis is a variation of a more general theory, hormesis … A good example of hormesis is exercise. In theory, this should damage cells because it increases oxygen uptake, and oxidative stress is bad for things like DNA. Of course, exercise is not actually bad for cells?and the reason is that the body activates defence mechanisms which overcompensate for the stress the exercise creates, producing beneficial effects. So, while chronic stress is always bad for you[3], a short period of mild stress followed by a period of recovery can be good.

More on hormesis here.

So what’s the common denominator between exercise, resveratrol, and caloric restriction? Stress. The introduction of acute stress may switch the body’s resources from reproduction to self-preservation4. From an evolutionary perspective, this makes sense. If a band of human beings were facing environmental hardship, such as a famine, their bodies would need to self-preserve until times more suitable for the ultimate biological imperative, reproduction.

Beyond acute stress causing self-preservation and thereby slowing aging, there may be another angle here: insulin. Caloric restriction will reduce insulin loads on the body as entering a fasted state will require the body to switch from glucose-burning (Insulin upregulated) to fat-burning (Insulin downregulated). As I’ve blogged before, chronically high insulin (via diets high in carbohydrates) in the blood is positively correlated to metabolic syndrome or Syndrome X. The connection to slowed aging and lower insulin levels could just be the other side of the same coin, but if nothing else, it’s more support for incorporating some amount of caloric restriction in your life.

Footnotes:

1 I’ve got a question out to the author, Nicholas Wade, as to his last claim regarding caloric restriction and its impact (or lack thereof) on humans. I’m fairly certain that Wade means that the life-extending impact of caloric restriction has yet to be proven for humans, even though the CALERIE study mentioned above would contradict such a claim.

I take serious issue with Wade’s ambiguity here. Most of his article is about resveratrol and sirtuins and their potential link to slowing aging in humans. He goes into detail about a pharmaceutical company that is working on producing a drug that might induce the same effects. That’s fine, but why slam the door on an alternative (caloric restriction) that might slow aging for free? Is it because it’s “far too hard for most people”? How did he determine that?

Update 2008-06-13: Received a response to my email to Nicholas Wade. From part of my email:

Or do you mean that sufficient testing on caloric restriction’s impact on human aging has not occurred, thereby the theory remains unproven?

He indicated that the above interpretation was the one he intended. I will let him know about the CALERIE study.

2 Here is the official CALERIE website.

3 Perhaps therein lies some support for the claim that endurance training is unhealthy as it puts a chronic load of stress on the body.

4 Not surprisingly, Art De Vany mentions as much in passing here:

I practice intermittent caloric deprivation. This is a known enhancer of the immune system. This is pure evolutionary reasoning. During deprivation, the system reallocates resources from reproduction to repair and maintenance. The immune system is part of that adaptation.