Mitochondria are the structures in which the chemical reactions that power a cell occur, and they undergo age-related damage from metabolism

Mitochondria are the structures in which the chemical reactions that power a cell occur, and they undergo age-related damage from metabolism. 

When comparing a young rat's brain cell (above) with an old rat's brain cell (below), the deterioration of mitochondria—the large sausage-shaped objects—is visibly apparent. 

A human brain cell may house well over a thousand mitochondria. Each one reproduces independently and lives for about two weeks.

Free radicals are highly reactive molecules that ravage the innards of cells. Free refers to the fact that these compounds are misfits, with no proper place in cellular society. 

Radical is the name biochemists give to an atom or molecule with an unpaired electron. Unattached free radicals bond indiscriminately with other molecules, stripping them of electrons with disastrous results—broken chromosomes, crippled enzymes, and punctured membranes. 

The electron-stripping process is called oxidation, and in controlled circumstances it's a vital part of ordinary cellular metabolism.

But free radicals are more like toxic waste. They leak from energy-making organelles called mitochondria; they spew from disease-fighting blood cells. 

Although cells have built-in mechanisms for cleaning up free radicals, the oxidants ultimately get the upper hand. 

In the mid-1950s, Denham Harman, a physician and chemist in the Donner Laboratory of medical physics at Berkeley, proposed that the cumulative damage wreaked by free radicals was largely responsible for the aging process. 

Today his free-radical theory is the most widely accepted model of aging.

Ames's research on oxidation led him to look more closely at mitochondria because they are the mother lode of free radicals. 

In order to burn fats and carbohydrates to make metabolic fuel, mitochondria take electrons from oxygen and shuffle them among a suite of molecules in a complex chain reaction. Invariably, some of the electrons get misplaced, creating free radicals. 

"People have estimated that [the electron transport chain] is maybe 98 percent efficient, which is much better than a human engineer can do," says Ames. "But it still makes kilos of oxygen radicals per person per year."

Mitochondria produce more oxidants than any other single site in a cell, the main offenders being superoxide, hydrogen peroxide, and hydroxyl radicals. Ames thought mitochondria would therefore be hardest hit by free-radical damage, not only to mitochondrial DNA but also to enzymes in the electron transport chain and lipids in mitochondrial membranes.

It also occurred to him that mitochondria might be an ideal target for intervening in the aging process. Working with postdoctoral student Tory Hagen, Ames characterized the changes that occur in the mitochondria of aging rats. 

They have shown that old mitochondria consume less oxygen, have stiffer membranes, and shuffle electrons less efficiently than their younger counterparts. Old mitochondria also make a lot more oxidants.

Ames decided to add an agent to the rats' diet to neutralize the oxidants. He tried lipoic acid, a mitochondrial antioxidant. The results were profound. 

Oxidants and oxidative damage to mitochondrial components dropped dramatically. Both the structure and function of the mitochondria improved. The rats' activity levels doubled. They were, Ames says, "doing the Macarena." 

The combination of the nutrient and the antioxidant had a synergistic effect. "The two together are better than either one alone."


http://discovermagazine.com/2002/oct/featradical