Why A Low-Calorie Diet Extends Lifespans: Critical Enzyme Pair Identified

[steven johnson]

Extrapolating the data mice to humans of the effects of caloric restriction on lifespan, would predict that our lifespan could go from 75 to 90 years 120 to 150 years with caloric restriction. Okinawans have many more centarians than on mainland Japan were the caloric intake is at least 20% lower as children and the death rates from vascular disease, malignancies, and heart disease were 59%, 69%, and 59%, respectively, of those of the rest of Japan.

In the US since 1981, life expectancy at 65 years has remained constant at 19 years, after a steep rise in the 1930s. The epidemic of obesity may have negated advances in other areas to prevent further increases in lifespan in this country.

Experimental metabolic manipulations may be the last frontier for increasing lifespan.

Caloric Restriction and Life Expectancy

ScienceDaily (June 28, 2009)

Experiment after experiment confirms that a diet on the brink of starvation expands lifespan in mice and many other species. But the molecular mechanism that links nutrition and survival is still poorly understood. Now, researchers at the Salk Institute for Biological Studies have identified a pivotal role for two enzymes that work together to determine the health benefits of diet restriction.
When lacking one enzyme or the other, roundworms kept on a severely calorie-restricted diet no longer live past their normal lifespan, they report in the June 24, 2009, advance online edition of the journal Nature.

Although lifestyle factors such as obesity clearly influence life expectancy, genetic factors are considered central to the process of aging. To date, there are only three known genetic networks that ensure youthfulness when manipulated. One centers on the insulin/insulin growth factor-1, which regulates metabolism and growth; the second is driven by mitochondria, the cell's power plants; and the third is linked to diet restriction.

When she genetically engineered worms to overexpress WWP-1, well-fed worms lived on average 20 percent longer. Deleting PHA-4, which was discovered in Dillin's lab and so far is the only gene known to be essential for lifespan extension in response to diet restriction, abolished the life-extending effects of additional WWP-1 placing the ubiquitin ligase as a central rung on the same genetic ladder as PHA-4. Without WWP-1, cutting down on calories no longer staved off death.

When a study by others found that UBC-18 interacts with WWP-1, Carrano wondered whether it could play a role in diet-restriction-induced longevity as well. She first confirmed that the UBC-18 functions as an ubiquitin-conjugating enzyme and gives WWP-1 a hand. She then tested whether it played a role in lifespan regulation. "Overexpression of UBC-18 was not enough to extend the lifespan of worms but depleting it negated the effects of caloric restriction," says Carrano, who is busy looking for potential substrates of the UBC-18-WWP-1 ubiquitination complex.



Why A Low-Calorie Diet Extends Lifespans: Critical Enzyme Pair Identified

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[cliffordu]

1. Or maybe it just FEELS like you're living longer....

[SmileyRose]

2. I doubt it's the calories.

In order to satisfy hunger and have energy at 20% lower calories would require a diet very heavy in fruit veggies and whole grains - meaning those kids got better nutrition early on. I'm just guessing that would set someone up to live longer - and of course - once the genetics of previous Okinawans gets spread around the gene pool that could create a society of longer livers too.

[Aragorn]

5. it's the calories

although that past research was not emphasized in this post - this study does probably explain HOW the calories make a difference, enzymatically.

[nightrain]

3. yeah, but what other effects? quality of life matters more to me than

quantity.

[fasttense]

4. It's probably more complicated in humans.

If caloric restriction alone were enough to extend life, then anorexic people and those in severe poverty would be living much longer. I really believe that in humans it is a much more delicate balance.

It has been shown statistically that elderly people who are about 10 lbs overweight live the longest in the US. Being too thin, especially in women, can lead to calcium deficiencies and the inability to fight off illness. In the 1930s many people were restricted in their caloric intake and they certainly didn't live longer. It seems that humans are designed to be at their best when they are in the middle of the bell curve.

Okinawans probably are eating the right foods besides reducing their caloric intake. Though on average, it wouldn't hurt US citizens to reduce their intake.