Sci. Aging Knowl. Environ., 7 July 2004
Spiraling Toward Death
Swirly mitochondria are associated with flies' demise
Cinnamon rolls are bad for dieters, and mitochondria that resemble cinnamon rolls don't do fruit flies any favors, either. Insects that accumulate these abnormal structures die early, new research shows. The swirls arise in response to oxidative stress and as flies age, offering researchers a visible marker for both processes.
One popular theory of aging holds that waste products of metabolism beat up cells (see "The Two Faces of Oxygen"). Most of the destruction occurs in mitochondria, which extract energy from food. To understand the connection among mitochondria, oxidative stress, and aging, researchers have exacerbated damage by housing flies in 100% oxygen. This treatment cuts life span from 2 months to about a week. Walker and Benzer wanted to identify the first faults to appear under such conditions.
The researchers pumped 100% oxygen into the flies' abodes and scrutinized cross sections of their flight muscles under an electron microscope. After 4 days at full oxygen, one-third of the mitochondria contained swirls of crimped membranes; after a week, 62% of them did. Flies of the same age that breathed normal air harbored swirls in only about 2% of their mitochondria. In another experiment, the researchers showed that insects younger than 12 days old carried few swirls, but the whorls were widespread in those older than 56 days. To gauge the power-producing capacity of the mitochondria, the researchers bathed muscle in chemicals that darken when energy-making proteins are active. Mitochondrial regions lacking swirls functioned normally, whereas the swirls remained light. Flies at high oxygen carried a particular mitochondrial protein that unravels just before cells commit suicide, but control insects didn't, suggesting that the swirly cells were doomed.
To uncover genes that help maintain mitochondria, the researchers wanted to pinpoint mutations that affect swirl accumulation. So they grew flies with random mutations in high oxygen and collected the bugs that died quickly. The fastest dying strain, called hyperswirl, keeled over after a day of breathing 100% oxygen. Even in normal air, hyperswirl flies accrued a mass of mitochondrial whorls by the age of 1 week and lived only about 25% as long as normal. The researchers are trying to identify the gene that's altered in this strain. In addition, they are studying other mutants that live longer than normal in concentrated oxygen to determine whether fewer swirls gather.
The work supports the idea that oxidative damage contributes to aging by eroding mitochondria, says molecular biologist Arlan Richardson of the University of Texas Health Science Center in San Antonio. He adds that because the swirls are obvious and easy to generate, flight-muscle mitochondria might be a tool for studying how the organelles' decay affects aging. Molecular biologist John Tower of the University of Southern California in Los Angeles predicts that swirls "will allow researchers to get a handle on molecular events in mitochondrial damage" by helping reveal mutations that speed up or slow down their formation. In any event, cellular cinnamon rolls could be the food of champions for researchers who study aging.
July 7, 2004
Suggested by Nick Bishop.
Science of Aging Knowledge Environment. ISSN 1539-6150