Sci. Aging Knowl. Environ., 13 August 2003
Vol. 2003, Issue 32, p. nw112
[DOI: 10.1126/sageke.2003.32.nw112]

NOTEWORTHY ARTICLES

Suffocating Aging

New model proposes that age-retarding mutations make worms go anaerobic

R. John Davenport

http://sageke.sciencemag.org/cgi/content/full/sageke;2003/32/nw112

Key Words: fumarate reductase • succinate dehydrogenase • electron transport chain • complex II

We all hope to age like a fine wine, and a new theory suggests that to do so, we should ferment too. Researchers now posit that long-lived Caenorhabditis elegans mutants endure because they shift to anaerobic respiration, an energy-production process that doesn't use oxygen. If experiments confirm the idea, they'll suggest that many life-extending mutations funnel into the same pathway.

Tweaks to genes that aid energy generation in mitochondria, the cell's power plants, can delay a worm's demise (see "Running Low But Long" and "Long Life Starts Early"). Such manipulations might limit production of reactive oxygen species, a possible cause of aging (see "The Two Faces of Oxygen"). But they should also impair energy production, leading researchers to wonder how such animals survive. Molecular geneticists Shane Rea and Thomas Johnson of the University of Colorado, Boulder, wondered whether these genetic changes extend life by prodding worms to pursue new metabolic strategies.

The researchers started their investigation with a mutation called clk-1, which disrupts production of ubiquinone, a molecule that shuttles electrons between proteins in mitochondria. This transfer helps generate the driving force that mitochondria use to produce ATP, the cell's energy currency. Rea and Johnson wondered if worms can bypass the need for ubiquinone. They searched the worm genome and found that the animals carry machinery that makes a related molecule called rhodoquinone. Rhodoquinone participates in an alternate energy-producing system that utilizes compounds produced during anaerobic respiration rather than ones manufactured during aerobic respiration. The clk-1 mutation might shift worm metabolism to a pathway that doesn't require oxygen, suggest Rea and Johnson.

Other seemingly dissimilar age-retarding mutations might work the same way, say the authors. For instance, some mutations in the insulin/insulin-like growth factor-1 (IGF-1) pathway prolong worm life. The pathway controls entry into the so-called dauer stage, which allows the creatures to survive harsh conditions such as drought, overcrowding, and food shortage. Dauers exploit anaerobic respiration, and life-extending insulin/IGF-1 mutations allow worms to survive oxygen starvation (see Longo Perspective). These results support the notion that such mutations prolong life by shifting worms into an oxygen-free mode. Mammals don't harbor the same anaerobic system that worms do, Rea notes, but they might possess other alternative methods for extracting energy from food. Altering metabolic strategy to prolong life might prove to be universal. Saccharomyces cerevisiae also make a shift but in the opposite direction: toward aerobic rather than anaerobic respiration (see "High-Octane Endurance").

"It's a great model," says molecular biologist Gordon Lithgow of the Buck Institute for Age Research in Novato, California. "It's provocative and easily testable." He says the researchers will need to track chemical intermediates in the metabolic processes and tinker with the enzymes involved to put the theory through its paces. Molecular biologist Laura Hoopes of Pomona College in Claremont, California, adds that the model might bring together disparate results in the field of worm aging. Further experiments should reveal whether the theory, like the bottle of Cabernet, is airtight.

--R. John Davenport; suggested by Arjumand Ghazi and Greg Liszt


August 13, 2003
  1. S. Rea and T. E. Johnson, A metabolic model for life span determination in Caenorhabditis elegans. Dev. Cell 5, 197-203 (2003). [Abstract] [Full Text] [CrossRef][Medline]
Citation: R. J. Davenport, Suffocating Aging. Sci. SAGE KE 2003 (32), nw112 (2003).








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