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标题：Prelamin A accumulation and stress conditions induce impaired Oct-1 activity and autophagy in prematurely aged human mesenchymal stem cell
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作者：Arantza Infante ; Andrea Gago ; Garbiñe Ruiz de Eguino 等
期刊名称：Aging
出版年度：2014
卷号：6
期号：4
页码：264-280
出版社：U.S.Department of Health & Human Service
摘要：Aging, a time-dependent functional decline of biological processes, is the primary risk factor in developing diseases such as cancer, cardiovascular or degenerative diseases. There is a real need to understand the human aging process in order to increase the length of disease-free life, also known as "health span". Accumulation of progerin and prelamin A are the hallmark of a group of premature aging diseases but have also been found during normal cellular aging strongly suggesting similar mechanisms between healthy aging andLMNA-linked progeroid syndromes. How this toxic accumulation contributes to aging (physiological or pathological) remains unclear. Since affected tissues in age-associated disorders and in pathological aging are mainly of mesenchymal origin we propose a model of human aging based on mesenchymal stem cells (hMSCs) which accumulate prelamin A. We demonstrate that prelamin A-accumulating hMSCs have a premature aging phenotype which affects their functional competence in vivo. The combination of prelamin A accumulation and stress conditions enhance the aging phenotype by dysregulating the activity of the octamer binding protein Oct-1This experimental model has been fundamental to identify a new role for Oct-1 in hMSCs aging.
关键词：human mesenchymal stem cells; aging; prelamin A; human aging models; Oct-1; autophagy