Sci. Aging Knowl. Environ., 7 August 2002
Die-hard worms might temporarily reverse aging
Key Words: aconitase reductive capacity lipofuscin catalase SOD
Abstract: A week of mud baths and spa pampering can make you feel years younger, but a bracing dose of adversity might turn back life's clock, according to a new study. As they emerge from a dormant state provoked by starvation, nematodes briefly reverse aging, restoring their metabolism to youthful fettle. If confirmed, this would be the first time animals have been caught performing the time-defying feat.
When the going gets tough, young nematodes get torpid. Starvation and crowding can prompt larvae to morph into a stress-resistant form called a dauer. An animal version of a spore, a dauer doesn't eat or grow and rarely moves. A nematode can while away more than 50 days in the dauer stage, four times its normal life-span. After abandoning its ascetic ways, the worm matures into an adult with normal longevity. Most scientists assumed that the dormant worms vacation from aging, possibly through reduced metabolism and increased activity of antioxidant enzymes. After awakening, the worms resume normal aging, the hypothesis went.
Koen Houthoofd, a biochemist at Ghent University in Belgium, and colleagues wanted to determine whether dauers do shrug off senescence. They measured the worms' metabolic prowess. In nondauers, oxygen consumption and heat production--both indicators of metabolic rate--decline with age. But neither measure slumped in dauers, even after 6 weeks, which suggests that the animals were frozen in time. However, other gauges of performance signaled deterioration. Adenosine triphosphate (ATP) concentrations in the worms gradually shrank, for example, and the creatures accumulated a skin pigment that colors old adults. Their mitochondria also started to run rough; the organelles' energy-generating capacity shrank 75% in 4 weeks, for example, and activity of a metabolic enzyme called aconitase dipped. Overall, the evidence suggests that dauers do age, although at a slower rate than adults do, says Houthoofd.
When the team roused some dauers with a buffet of bacteria, the indicators of aging flip-flopped. ATP concentrations soared to youthful values, mitochondrial capacity and aconitase activity boomed, and the worms lost their elderly tinge. This "metabolic explosion" occurred within a few hours, and afterward the worms developed and aged normally. "The aging clock can be reset," says Houthoofd. However, rejuvenation returns the worms only to their predauer condition. Once they start slithering and feeding again, they last no longer than nematodes that never entered dauerhood.
The researchers don't know what sparks the recovery, but they suspect that worms are refurbishing or replacing their battered mitochondria, says Houthoofd, a scenario that is consistent with the notion that mitochondrial damage drives aging. The study demonstrates that, contrary to popular wisdom, dauers decline, says Pam Larsen, a molecular geneticist at the University of California, Los Angeles. However, she says, whether we define their recovery as reversed aging or as rapid healing--a well-known power of young animals--is a matter of semantics. Harnessing the worms' ability to promptly refresh their mitochondria might someday help keep our own cells fit, she adds. Staying young might take only a jolt of dauer power.
K. Houthoofd, B. P. Braeckman. I. Lenaerts, K. Brys, A. DeVreese, S. Van Eygen, J. R. Vanfleteren, Ageing is reversed, and metabolism is reset to young levels in recovering dauer larvae of C. elegans. Exp. Gerontol., 16 July 2002 [e-pub ahead of print]. [Journal Home Page] [Until paper appears in print, see "Articles in Press."]
Citation: M. Leslie, Dauer Power. Science's SAGE KE (7 August 2002), http://sageke.sciencemag.org/cgi/content/abstract/sageke;2002/31/nw110
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