Is there an anti-aging gene?


A mouse unconcerned with living longer
A mouse unconcerned with living longer
© iStockphoto/rdegrie

If you were a child or had a child sometime after 1985, then you may be familiar with Laura Joffe Numeroff's book "If You Give a Mouse a Cookie." In the book, we learn that if you give a mouse the aforementioned cookie, he'll want a glass of milk, which will lead into a whole host of requests on the part of the mouse -- an entire laundry list of demands that might try the patience of even the most giving soul. The next time you're considering giving a rodent a treat, though, consider this: If you don't give that mouse the cookie, he could live forever.

That's not just the premise for another adorable children's book; scientists have known since the 1930s that restricting the caloric intake of mice causes them to live much longer than they might otherwise. Same goes for other creatures, like worms and fruit flies. Now, you might be thinking that you don't really care if mice live longer, particularly if they're greedy creatures in constant need of milk and cookies, but what researchers are learning from these mice could have very important implications for us.

We need only glimpse at the number of fast food restaurants and the statistics of increasing childhood obesity to know that many of us would have a tough time with a calorie-restricted diet, and besides, this is no easy diet, no matter how strong your willpower. To increase their life spans by about 40 percent, the mice had to consume at least 30 percent fewer calories while still maintaining a diet that included all necessary vitamins and minerals [source: Mason].

That's a difficult diet, though there have been times when such a regimen would have served our ancestors. Evolutionary biologists believe that we may have developed the ability to use caloric restriction to prolong life in times of great famine. By eating less, we lived longer, but we were less likely to reproduce; this would have ensured that we weren't bringing forth young that would only starve. During times of plenty, we eat, we breed and then, having done our evolutionary duty, we die.

While researchers have figured out why such a diet would be useful and how to replicate the results in lab animals, it wasn't known until recently how the process of extending life through caloric restriction worked. As it turns out, the success of calorie restriction could be due to a single gene, and understanding this gene could have huge consequences for our own aging process.

SIRT1: The Human Anti-aging Gene

Scientists want to trigger the effects of caloric restriction without the hassle of restricting calories.
Scientists want to trigger the effects of caloric restriction without the hassle of restricting calories.
© iStockphoto/Kangah

"No pain, no gain" is the mantra of most diet and exercise programs. However, since a severely restricted diet isn't a good long-term solution for most people, scientists have been trying to find a way to create those same results without actually cutting the calories. What could trigger the body into thinking that it's consuming fewer calories?

Dr. Leonard P. Guarente, a biology professor at M.I.T., hit upon a potential answer when he was studying yeast cells in the mid 1990s. As expected, the cells lived longer when they were given very small amounts of food, and Dr. Guarente began manipulating the cells' genes to determine what part they played in the extended life span. When yeast cells undergoing caloric restriction were endowed with one certain gene, they lived even longer, and when that gene was eliminated by Dr. Guarente, the caloric restriction was for naught, and the yeast cells died. That gene was silent information regulator No. 2, or SIR2.

SIR2 appeared to stop the aging process by stopping the production of waste material in the cell, which allowed the cell to work better for longer. Dr. Guarente was able to duplicate his results with another small organism, the roundworm, which demonstrated that this gene played a role in extending longevity during periods of caloric restriction in several different species. But what of humans?

It turns out humans don't have SIR2, but we have a gene that appears to do the same thing: SIRT1. Both SIR2 and SIRT1 seem to work the same way in the body; they're charged with repairing DNA within the body and suppressing certain genes. Gene silencing, as this suppression is called, is important because if the wrong genes become activated, then the cell's function could be destroyed. It may be that cases of Alzheimer's and diabetes occur because of this type of genetic malfunction.

Dr. Guarente believes that as we age, it's harder for SIR2 and SIRT1 (collectively known as sirtuins) to multitask, so that this gene silencing falls by the wayside. As a result, we end up with the conditions we associate with old age, like cancer, heart disease and the aforementioned Alzheimer's and diabetes. It seems that caloric restriction is so effective because it helps sirtuins work better within the body.

Still, if a calorie restricted diet is unrealistic, then how does knowing this help us live longer?

Resveratrol and Longevity

Resveratrol, an ingredient in red wine, may be the key to living longer.
Resveratrol, an ingredient in red wine, may be the key to living longer.
© iStockphoto/anzeletti

If caloric restriction, shown to increase life spans in lab animals, is effective due to an increase in SIRT1 and SIR 2 genes, how do we get those genes to kick in more often? It turns out there's an intermediary: Caloric restriction increases the amount of nictotinamide adenine dinucleotide, or NAD, in each cell. That's because NAD is normally converting all that glucose in your food into energy. With fewer calories, there's more NAD available, looking for something to do, and what they end up doing is spurring activity of SIR2 and SIRT1. Thus, the current task for researchers is to find something that acts like NAD in terms of activating these anti-aging genes. If they can find this magic bullet and put it into pill form, then humans could take this pill, maintain their current diets and live longer.

One potential sirtuin regulator receiving a good deal of attention is resveratrol. You may be familiar with resveratrol as an ingredient in grape skins; it's present in greater amounts in red wine as opposed to white. In the lab, our old friends the yeast cells lived 70 percent longer when given resveratrol [source: Wade]. Mice benefit as well: Lab mice who were fed a high-fat diet lived about as long as you'd expect them to, while mice on the high-fat diet in combination with resveratrol lived longer, seeming to indicate that resveratrol can simulate caloric restriction and activate those anti-aging genes [source: Wade].

Scientists still have work to do in terms of applying these results to humans, simply because humans already live so much longer than mice and yeast cells -- imagine how many years we'll have to sit around to see if increased resveratrol had any difference in the case of a 50-year-old man. However, we do know that the answer isn't just a glass of red wine a day to stimulate SIRT1. To consume as much resveratrol as those mice were getting, a 150-pound (68-kilogram) person would need to drink 750 to 1,500 bottles of red wine each day [source: Wade].

In addition to the time needed to study this subject, researchers interested in life extension have an uphill battle to climb in terms of perception. It's very easy for people to dismiss the idea of taking a pill to live longer as wishful hocus-pocus, and it may not seem like a very pressing need when there are so many diseases that need treatments. However, as we mentioned previously, a good deal of disease comes upon us as we age. It's possible that slowing down the process of aging in the cells would eliminate these conditions.

For more on aging and how we might live longer, see the stories on the next page.


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Are you age smart?

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