p21 both attenuates and drives senescence and aging in BubR1 progeroid mice.
Publication year
2013Source
Cell Reports, 3, 4, (2013), pp. 1164-1174ISSN
Publication type
Article / Letter to editor

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Organization
Cell Biology (UMC)
Journal title
Cell Reports
Volume
vol. 3
Issue
iss. 4
Page start
p. 1164
Page end
p. 1174
Subject
NCMLS 4: Energy and redox metabolism IGMD 8: Mitochondrial medicineAbstract
BubR1 insufficiency occurs with natural aging and induces progeroid phenotypes in both mice and children with mosaic variegated aneuploidy syndrome. In response to BubR1 insufficiency, skeletal muscle, fat, and lens tissue engage p19(Arf) to attenuate senescence and age-related deterioration. Here, we address how p19(Arf) exerts this caretaker role using BubR1 progeroid mice lacking p53 or its transcriptional target p21. We show that p53 delays functional decline of skeletal muscle and fat in a p21-dependent fashion by inhibiting p16(Ink4a)-mediated senescence of progenitor cells. Strikingly, p53 also attenuates the formation of cataractous lenses, but here its antiaging effect is p21 independent, as we found p21 to promote senescence of lens epithelial cells and cataract formation. Together, these results demonstrate that p53 counteracts tissue destruction in response to BubR1 insufficiency through diverse mechanisms and uncover a causal link between senescence of the progenitor cell compartment and age-related dysfunction.
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- Academic publications [204996]
- Electronic publications [103294]
- Faculty of Medical Sciences [81051]
- Open Access publications [71819]
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