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Sci. Aging Knowl. Environ., 5 April 2006
Vol. 2006, Issue 7, p. pe9
[DOI: 10.1126/sageke.2006.7.pe9]

PERSPECTIVES

Aging in Check

Wei Dai, and Xiaoxing Wang

The authors are in the Division of Molecular Carcinogenesis of the Department of Medicine, New York Medical College, Valhalla, NY 10595, USA. E-mail: wei_dai{at}nymc.edu (W.D.)

http://sageke.sciencemag.org/cgi/content/full/2006/7/pe9

Key Words: spindle checkpoint • aneuploidy • chromosome instability • senescence • p53 • mosaic variegated aneuploidy syndrome

Abstract: The spindle checkpoint monitors the interaction between spindle microtubules and kinetochores to prevent precocious entry into anaphase, delaying this stage of mitosis until all condensed chromosomes have been attached to the mitotic spindle in a bi-oriented manner (so that the two kinetochores associated with a pair of sister chromatids are oriented toward opposite poles of the spindle). In addition to conserved Bub and Mad family members, which are known to function in the spindle checkpoint pathway in organisms ranging from yeast to mammals, two mRNA transport genes, Rae1 and Nup9, are also involved in the spindle checkpoint function in mammals. Biochemically, activated spindle checkpoint components have been shown to suppress the activity of the anaphase promoting complex/cyclosome. It is generally thought that decreased activity of the checkpoint components predisposes cells to chromosomal instability, aneuploidy, and malignant transformation. Interestingly, a recent study has shed light on a new function of the spindle checkpoint components Bub3 and Rae1 in the regulation of aging. Mice with haploinsufficiency of Bub3 and Rae1 have a short life span that is associated with the early onset of aging-related features. The progeroid phenotypes caused by deficiency of Bub3 and Rae1 are tightly linked to precocious activation of cellular senescence, but not apoptotic, programs. Therefore, premature aging, rather than neoplastic transformation, may be the major manifestation of a compromised spindle checkpoint in vivo.

Citation: W. Dai, X. Wang, Aging in Check. Sci. Aging Knowl. Environ. 2006 (7), pe9 (2006).

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Science of Aging Knowledge Environment. ISSN 1539-6150