Sci. Aging Knowl. Environ., 6 April 2005
Older mitochondria lose their oomph
Like California air conditioners in the summer of 2000, an elderly person's muscles run low on power. The brownouts stem not from the shenanigans of unscrupulous energy brokers but from faltering mitochondria, a new study shows. The work suggests that DNA damage in the cellular power plants unleashes changes that sabotage energy production.
Mitochondria use food energy to fashion adenosine triphosphate, which fuels cell activities (see Nicholls Perspective). But the tiny powerhouses also emit noxious byproducts called reactive oxygen species (see "The Two Faces of Oxygen"). The organelles accumulate damage, which many researchers suspect spurs some of the problems that plague the elderly, such as muscle weakness. Studies have found that glitches in mitochondrial DNA amass over time, and last year, researchers showed that mice with a faulty DNA proofreading protein in their mitochondria aged faster than normal (see "Symphony of Errors"). However, results conflict about whether mitochondrial energy output falls with age in people. Some studies focused on mitochondria isolated from patients with metabolic disorders, and others didn't account for variation in physical fitness among subjects or neglected to use a range of age groups, says endocrinologist K. Sreekumaran Nair of the Mayo Clinic College of Medicine in Rochester, Minnesota. He says that these and other differences in methods may account for the discrepancy in results. Nair and colleagues set up a study to overcome these problems.
The team rounded up 146 healthy patients between 19 and 89 years old who exercised about the same amount. The researchers measured the subjects' aerobic capacity, an indicator of maximum metabolic production. They also gauged the ability to absorb blood glucose after a meal, deficits in which ability can presage diabetes. Both measures declined with age. When the team analyzed mitochondria from the patients' thigh muscles, they found that the power plants' energy production also plunged over time, shrinking by about 8% per decade of life. Moreover, falling mitochondrial output correlated with declining aerobic capacity and reduced ability to handle blood glucose. That result suggests that deteriorating mitochondria might undermine the muscles' response to sugar. The researchers also determined that the amount of DNA packed into each organelle dwindled. This reduction may account for the finding that elderly patients made less of several key mitochondrial proteins than did youngsters. The amount of DNA with oxidative damage rose with age, the team showed. This type of injury to mitochondrial DNA may trigger a chain of events that culminates in falling energy output, says Nair. The question now, he says, is whether we can intervene to break the chain.
"This paper nicely supports mitochondrial theories of aging and shows possible mechanisms for how energy deficits could result," says molecular biologist James Sligh of Vanderbilt University Medical Center in Nashville, Tennessee. What sets the study apart is that it shows that "physiological changes [such as aerobic capacity] correlate to molecular changes," says Bennett Van Houten, a molecular biologist at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina. Now researchers want to tinker with these cellular generators to keep the power flowing.
April 6, 2005
Science of Aging Knowledge Environment. ISSN 1539-6150