Lamin A-dependent nuclear defects in human aging

被引：882

作者：

Scaffidi, P ^{[1
]}

Misteli, T ^{[1
]}

机构：

[1] NCI, NIH, Bethesda, MD 20892 USA

来源：

SCIENCE | 2006年 / 312卷 / 5776期

关键词：

D O I：

10.1126/science.1127168

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Mutations in the nuclear structural protein lamin A cause the premature aging syndrome Hutchinson-Gilford progeria (HGPS). Whether lamin A plays any role in normal aging is unknown. We show that the same molecular mechanism responsible for HGPS is active in healthy cells. Cell nuclei from old individuals acquire defects similar to those of HGPS patient cells, including changes in histone modifications and increased DNA damage. Age-related nuclear defects are caused by sporadic use, in healthy individuals, of the same cryptic splice site in lamin A whose constitutive activation causes HGPS. Inhibition of this splice site reverses the nuclear defects associated with aging. These observations implicate lamin A in physiological aging.

引用

页码：1059 / 1063

页数：5

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