Strong Spirit, Weak Flesh
Authors: Beckman Mary 
Published: August 2003

Like some politicians, nematode nerves seem to be above the law, new research shows. Muscle appears to follow the rules of aging, falling apart with time. Neurons, however, have written their own legislation and remain pristine and youthful, even as the worm withers. The results suggest that a regulatory system ages some worm cells but not others and that researchers might be able to use nematodes to understand muscle aging in humans.

Until this summer, scientists who study aging in
Caenorhabditis elegans
could rely only on endpoints--prolonged life or premature death--to assess what makes animals grow old. Such studies might uncover long-lived worms, but they don't reveal whether the animals are living productively or merely gripping the deathbed with white knuckles. Several months ago, researchers reported what normally aging worms look like under the microscope (see
"Gauging Aging"
) and showed that a well-known longevity factor delays tissue degeneration. Now, a different team has turned up the magnification on nematodes and found that different physiological systems do not age at the same rate.

To examine aging in specific tissues, Herndon and colleagues marked either muscle cells or neurons in different worms with fluorescent molecules. Then they zoomed in on the tissues under a light microscope and with the higher magnification of an electron microscope. The worm's nervous system appeared intact throughout life, even in the most decrepit animals. Turning to the muscles, the team saw signs of deterioration starting in middle age, around day 7. The degeneration progressed steadily into old age, much like sarcopenia, the progressive decline of human muscle mass. Long, thin structures that allow muscle cells to push and pull, called sarcomeres, were neatly stacked in young adult animals but had chipped and frayed in elderly nematodes. Long-lived mutants remained strong, however: Muscle cells from 11-day-old

age-1

mutants looked as healthy as did those from 7-day-old normal worms. The differences lasted until day 14, at which point the mutant cells looked like normal cells of the same age, indicating that the mutation delays the onset of muscle aging but that mutant worms eventually catch up to their frail cronies.

The fact that neurons don't seem to age is "the main cool thing," says molecular biologist Cynthia Kenyon of the University of California, San Francisco. "The normal animal has the ability to prevent aging in some cells and not others. What might regulate that?" The
age-1
mutation disrupts an insulin-like signaling pathway that promotes aging (see
Bartke Viewpoint
); the neurons could be resistant to the pathway's effects, she suggests, although that's just a guess. The similarity of worm muscle degeneration to sarcopenia raises the possibility that we can use worms to understand muscle aging in humans, says muscle biologist Thomas Rando of Stanford University. "One of the problems with the study of aging is that we don't know why [organisms] die," he says. "We need to connect life-span to cell and tissue biology." Knowing the rules of bodily degeneration might help researchers raise humans above the law.

--Mary Beckman

L. A. Herndon, P. J. Schmeissner, J. M. Dudaronek, P. A. Brown, K. M. Listner, Y. Sakano, M. C. Paupard, D. H. Hall, M. Driscoll, Stochastic and genetic factors influence tissue-specific decline in ageing
C. elegans
.
Nature
419
, 808-814 (2002).
[Abstract]
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