Sci. Aging Knowl. Environ., 17 December 2003
Vol. 2003, Issue 50, p. nw171
[DOI: 10.1126/sageke.2003.50.nw171]


Fear Factor

Timid mice die sooner than more adventurous siblings

R. John Davenport

Key Words: neophobic • neophilic • adrenal • amygdala

Shrinking violets, beware: An aversion to novelty presages an early death, according to new work. The research reveals that fearless rodents outlive their nervous brothers, perhaps because trepidation triggers the release of stress molecules.

New situations can enrich a person's life, but novelty causes some individuals stress. Brain activity associated with anxiety ignites a hormone cascade that provokes the production of glucocorticoids, molecules that spur the body to mobilize fuel reserves for "fight or flight." Small amounts of stress can bolster the body (see "Stress for Success"), but long-term disquiet can wear it down, depleting energy, dampening immunity, and killing neurons. Researchers have connected an ability to withstand stress with extended life span; for instance, most long-lived fly and worm mutants tolerate chemical or other insults unusually well. But no one had connected the tension induced by fearfulness with changes in life span.

To address that issue, Cavigelli and McClintock assessed rat behavior by placing young animals in a box filled with unfamiliar objects and measured how much each animal explored the items; more movement indicates less fearfulness. Based on this test, they gathered pairs of male rats--a fearful rodent and a fearless one--from 14 different litters. Animals behaved consistently at several points in their lives, suggesting that rats don't experience dramatic changes in courage over time. Reticent animals generated more glucocorticoids after being exposed to new objects than did those that sought out the novel objects, a result that agrees with previous studies.

Next, the team waited for the animals to keel over. At any age, skittish animals were 60% more likely to die than the more adventurous animals were. And the oldest of the daring critters lived about 20% longer than did their most ancient lily-livered counterparts. Individuals in each group developed tumors at the same rate, and none of the rodents showed signs of infection, suggesting that all of the animals died of similar causes. Further work is needed to determine whether glucocorticoids or some other factor is responsible for the risk-avoiding animals' untimely demise.

If experiments that use different rat strains and different behavioral tests verify the result, it's "extremely significant," says Jerome Kagan of Harvard University. He adds that this is the first study to connect fearfulness at a young age with a shortened life span. Neuroendocrinologist Bruce McEwen of the Rockefeller University in New York City, who edited the paper for the Proceedings of the National Academy of Sciences, says that the work shows that "we have to take seriously the impact of individual behavioral and related physiological differences early in life in determining trajectories of health and disease." Similar behavioral differences could influence life span in humans, says Kagan, but timid individuals lead more cautious lives, and their decreased likelihood of accidental death could outweigh any intrinsic shortening of life. One conundrum, says physiologist Mary Dallman of the University of California, San Francisco, is that calorie restriction--which extends life in rodents and other organisms--elevates, rather than lowers, glucocorticoid amounts. Understanding more about why adventurous rats live long could help resolve that discrepancy--and clarify whether reducing fear could help wallflowers enjoy an extended bloom.

--R. John Davenport

December 17, 2003
  1. S. A. Cavigelli and M. K. McClintock, Fear of novelty in infant rats predicts adult corticosterone dynamics and an early death. Proc. Natl. Acad. Sci. U.S.A., 12 December 2003 [e-pub ahead of print]. [Abstract] [Full Text]
  2. R. S. Wilson et al., Proneness to psychological distress is associated with risk of Alzheimer's disease. Neurology 61, 1479-1485 (2003). [Abstract/Free Full Text]
Citation: R. J. Davenport, Fear Factor. Sci. Aging Knowl. Environ. 2003 (50), nw171 (2003).

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