Douglas C. Wallace
We believe that mitochondrial DNA damage is a major factor in aging, and that the cause of damage is the mitochondria generating oxygen radicals, which then attack their mitochondrial DNA
Mitochondria and Aging
Although it was a research subject sorely neglected for decades, the intriguing interplay of nuclear DNA, mitochondrial DNA and the flow of energy is now getting intense study worldwide, and the results may soon be stunning.
Importantly, such studies seem to offer key insights into the problems associated with aging, including rapid-aging disorders such as Werner syndrome, plus the aging-associated diseases that include cancer and diabetes.
From the perspective of aging, DNA damage more and more seems to reflect the accumulating harm being done to the enzymes and enzyme systems involved in sensing and regulating the energy supply. Because of oxidative damage done by reactive oxygen species, and by sloppy DNA repair, the evidence suggests the slow-down known as aging results from individual cells losing the ability to do their assigned jobs. Heart muscle cells pump less vigorously, communication among brain cells falters, and other organs show the signs of deterioration.
New Scholar Vera Gorbunova, at the University of Rochester, for example, is pursing the evidence that point mutations and erroneous chromosomal rearrangements that accumulate with age take a toll as error-correcting mechanisms become less effective with age.
She suspects that “in aging cells, the machinery for double-strand break repair becomes error-prone.” So research in this area may increasingly inform science about fundamental aspects of the aging process, and maybe even suggest corrective measures.
In contrast, Marion Schmidt is researching the other end of the equation, looking at the increase in mitochondrial dysfunction that goes along with aging. In work at the Albert Einstein College of Medicine of Yeshiva University, Schmidt and colleagues are focusing on a universally-conserved proteasome activator, Blm10, which appears to be essential for normal mitochondrial homeostasis.
In another approach, Kevin D. Mills, at The Jackson Laboratory, has focused his Ellison-supported research on the natural world, setting up to study several strains of well-characterized mice that are essentially normal. “I propose to investigate the connection between DNA damage and ‘natural’ variations in aging,” Mills said. To do that, he and his colleagues are studying 32 lines of genetically-defined young, middle-aged and old mice. It’s a rich resource that should allow them to follow any genetic factors involved in natural DNA repair, and try to learn how the errors may impact the aging process, as well as the diseases related to aging.
Also, because declining energy seems to be deeply involved in the aging process, Tina M. Iverson – at Vanderbilt University – is examining the delicate balance that exists between getting enough energy and avoiding the damage done by energy production in the mitochondria.
Thus Iverson’s team is looking into the molecular basis for the formation of ROS (reactive oxygen species) that are known to damage the DNA, proteins and membranes inside living cells. The goal, of course, is to identify novel treatments that will improve the aging process, helping people live longer and healthier lives.
These multiple avenues of research are all pulling in the same direction to help eliminate the debilitating chronic diseases that can often accompany old age.
See also: DNA Damage and Repair