How did the Mice Beat the Aging Process?

Dov Michaeli

First published 3/7/11 on The Doctor Weighs In

To Pat, on her birthday

At first it sounded like “so, this mouse walks into a bar and asks the bartender, guess how old I am” joke, but then on second thought…

But before we go on, remember the movie “The Curious Case of Benjamin button”? To refresh your memory, it’s about a person who was born 80 years old (yes, you read it right) and got progressively younger until he died as an infant some seventy years later. Before you laugh, let me remind you: that’s almost the reverse of Progeria, a rare condition that is remarkable because its symptoms strongly resemble normal human aging, but occur in young children (see picture above). Their head becomes shrunken, narrow and skin becomes wrinkled within a few years after birth. They are bald, lose their eyebrows, and they develop diabetes, hypertension, atherosclerosis, heart disease, and die mostly in their early teens of heart attacks or stroke. We also know that this disease is due to a single mutation in a gene called lamin A.

Those Pesky Mitochondria

Back to that mouse in the bar. A recent paper (Proceedings of the National academy of Sciences, Feb. 22, 2011) titled “Endurance exercise rescues progeroid (progeria-like; DM) and induces systemic mitochondrial rejuvenation in mtDNA (mitochondrial DNA; DM) mutator (mutation-bearing;DM) mice” is dead serious about the hard-to-guess age of the bar mouse.

Dr. Mark Tarnopolsky, a  professor of Pediatrics and a researcher of aging at McMaster university In Canada, and his group report on an intriguing experiment.  Epidemiologic studies in humans have demonstrated that endurance training reduces the risk of chronic diseases and extends life expectancy. But exactly how is this accomplished is unknown. Some clues are provided by recent studies demonstrating that the mtDNA mutator mouse, harboring a defect in an enzyme that is important in DNA repair, exhibits multisystem pathology, and reduced lifespan. So Tarnopolsky did a very simple, and ingenious experiment. They used the mice that had this mitochondrial mutation and divided them into two groups: group one led a sedentary life; group two exercised three times a week running on a wheel for 45minutes. They started their exercise at age 3 months, which is equivalent to 20 years in human age, and lasted until they were 8 months of age (equivalent to about age 65 in humans, ready for Medicare). The sedentary group, by the time they reached 8 months were frail, with spindly muscles, shrunken brains, enlarged hearts, shriveled gonads and bald and patchy graying fur. All were dead before reaching a year of age. And the exercising group? They had full pelts of dark fur. They also had maintained almost all of their muscle mass and brain volume. Their gonads were normal, as were their hearts. At 1 year, none of the exercising mice had died of natural causes (some were sacrificed for pathology studies).

Remarkable. Lest we forget –these mice overcame with exercise a genetic mutation they were harboring.

Does it have anything to do with real life?

Every 10 years we lose about 8% of the muscle mass. So by age 60 or 70 muscles shrink, brain volume drops, hair falls out or loses its pigmentation; in short –we are old, and we look it too. There is evidence that underlying this unfortunate process is an accumulation of mitochondrial mutations until they lose their function of providing energy to the cell, causing the cell’s death –and tissue loss. One more fact: endurance and resistance exercises not only stop this process, they cause and increase in the number of mitochondria per cell, preserving cellular health and increasing tissue volume. So in this respect the mouse experiment is almost a perfect mimic of the biological process of aging.

If you think that now we can devise a pill that will stop the mutagenesis of mitochondria –fuggedboutit! Not in our lifetime. We still know very little about mitochondrial DNA, and even less about the mitochondrial mutations that accumulate with aging.

There is only one way to counter the aging process: exercise; no shortcuts!

Dov Michaeli MD, PhD is, I guarantee, the fittest septegenarian you know. He writes at The Doctor Weighs In.

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