While reviewing past articles from the Digital Edition archive at Scientific American Magazine, I came across a 2002 article from my old lab at the Gerentology Research Center at the National Institute of Aging. The article describes a summary of what is known about the effects of caloric restriction on aging, lifespan, and disease.

In short, caloric restriction (CR) is simply the consumption of fewer calories, typically about 30% less, which has been demonstrated to decrease age-related disease, increase average lifespan, and increase maximum lifespan. While this has been well characterized in rodents, roundworms, and fruit flies, the most intriguing studies are being performed on populations of monkeys at NIH and the University of Wisconsin, which must go on for decades before confirming the effects of CR conclusively. In lieu of waiting some 20 or 30 odd years for those projects to complete, scientists can and do look at biologicial indicators that measure the aging process at various ongoing intervals.

As anyone on a typical diet can attest, eating less has the unwanted effects of making one grumpier and less able to focus or concentrate, and it's not very likely that people will really be able to stay on a calorically reduced diet for any significant amount of time, although Dr. Roy Walford is giving it his best try. Scientists hope to develop drugs to mimic the effects of caloric restriction, without actually requirnig humans to eat less. Although I'm personally still hoping that they will come up with one to help me drop the 30+ pounds I've put on since working in the software industry!!

Caloric restriction is believed to be tied to reducing oxidative stress. Oxidative stress is generally described as the deteriorating effects of the chemicals produced (hydroxyal radicals and super oxide) as a side effect of generating energy in the form of ATP while we burn the food we eat. As we get old the oxidative damage slowly accumulates. We naturally have physiological protectants and mechanisms for cellular repair, but as those mechanisms get damaged they in turn repair other cellular components less well.

Richard Cutler once explained to me that oxidative stress is analogous to a new car where at first we take care to polish and clean it, get the oil changed, and put in some effort to maintain it. But after a couple years the dings set in, the tire pressure drags, and maybe a gasket or two leaks. We become complacent and gradually pay less attention to the car until after quite a few years it becomes the old clunker that sits in the backyard. Our cells are kinda like that car, except its our own bodies and cells that take care of itself.

The Scientific American article I first referenced describes 2DG (2-deoxy-D-glucose) as being a leading candidate to mimic the effects of caloric restriction by preventing cells from metabolizing the glucose derived from all the calories we consume, therefore reducing the amount of oxidative by-products by simply metabolizing fewer calories. Although, as reported in the article, the CR mimetic 2DG has a very narrow theraputic range, bordering on toxicity and thus eliminating it as a drug candidate for humans, but the 2002 article did report that the authors were hopeful that a CR mimetic without serious side affects or possible toxicity would be found soon. A quick PubMed search just now didn't turn up any significant new information in this area.

Another approach to combat oxidative stress and age related declines is to increase the amount of antioxidants in the diet, including Vitamin E (alpha-tocopheral) and anthocynanins from blueberries, strawberries, and other red, blue or dark green fruits and vegetables, as well as (dark) red wine. It's those food pigments, the anthocyanins, that are the actual antioxidants. Those antioxidants enter our cells and buffer the oxidative damage, by definition of course. We can all take advantage of antioxidants in our current diet through changes to our daily regimen that don't necessarily mean eating less, but just eating better. Ever since I first saw the positive effects of antioxidant diets on rodents that I worked with (as well as antioxidant studies on brain tissue in vitro), I've added high amounts Vitamin E, blueberries, and spinach to my diet on a daily basis, including a glass of cabernet in the evening. While its too early to tell for me, be sure to check back say in 30 years.

The ultimate goal of this research is to help humans live longer lives, perhaps up to 100, 120, or more based on what's observed in other animal types, while living those years healthier and more productive along the way. This could mean that humans would be regularly living to well over 100 years old while still having the body and mind of someone in 60's or 70's today. By the way, since aggression and tendency towards war has been highly correlated with the percentage of young men in a population, this makes me wonder if a significant increase in the aged would stabilze our society and world overall, but that's for another blog.

To learn more on this topic see the following articles, including research from Dr. Roy Walford, a former scientist and physician in BioSphere 2 which unexpectedly put its inhabitants on a calorically restricted diet for 2 years when the BioSphere failed to produce the anticipated level of food. Richard Weindruch, frequent author and contributor to CR research, was Roy Walford's graduate student, and went on to lead the primate project in Wisconsin.