Published 13 February 2006. doi:10.1083/jcb1724iti1
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 172, Number 4, 481-481
Aneuploidy does not equal aging
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The muscles of a 19-month-old mutant look like those of a 35-month-old wild-type animal.
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Scientists have hypothesized that aneuploidy could be a driving factor in aging. On page 529, Baker et al. report evidence to the contrary.
Using a mutation series in the BubR1 mitotic checkpoint protein, the researchers previously showed that as the amount of functional protein decreased, aneuploidy increased, as did the rate of aging. To determine whether the correlation was causal, Baker et al. now compared the BubR1 mutants to mice carrying mutations in two other mitotic checkpoint genes, Bub3 and Rae1. The double mutant animals had significantly more aneuploidy than did the BubR1 mice. However, the double mutants reached old age at 18 to 24 months, which is about four months earlier than wild-type controls, whereas the BubR1 animals were completely aged at just five months.
There was a correlation in all strains tested between the rate of aging, cell senescence, and expression of the Rb and p53 stress response proteins. Both mutant strains, though, had nearly the same DNA repair capacity as did the wild-type animals, which leaves open the question as to what triggers the p53 pathway.
The severity of the mitotic checkpoint defect did not correlate with the rate of aging, and not all checkpoint genes accelerated aging when mutated. That may mean that the checkpoint proteins BubR1, Bub3, and Rae1 are working through a nonmitotic pathway to trigger p53 and senescence, and ultimately to control aging.
Rabiya S. Tuma
rabiya{at}nasw.org
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