期刊
CANADIAN JOURNAL OF CARDIOLOGY
卷 32, 期 5, 页码 650-658出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cjca.2015.12.003
关键词
-
资金
- Grants-in-Aid for Scientific Research [15H04806] Funding Source: KAKEN
Early human mummies examined recently by computed tomography demonstrated a high prevalence of vascular calcification, a pathognomonic sign of atherosclerosis, which was correlated with estimated age at death. Early populations had little exposure to modern-day metabolic risk factors: these observations thus suggest that humans have an inherent age-dependent predisposition to atherosclerosis. Premature aging syndromes are extremely rare genetic disorders that exhibit clinical phenotypes resembling accelerated aging, including severe atherosclerosis, but those phenotypes are usually segmental. Controversy persists, therefore, regarding the extent to which the molecular mechanisms underlying premature aging syndromes overlap with those of physiological aging. Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome are well-characterized premature aging syndromes. HGPS is caused by gain-of-function mutations in the LMNA gene, which result in the accumulation of a mutant nuclear protein, called progerin, at the nuclear rim. In contrast, loss-of-function mutations in Werner syndrome ATP-dependent helicase (WRN) lead to Werner syndrome. Mesenchymal stem cells (MSCs), which can differentiate into vascular cells to maintain vascular homeostasis in response to injury, are severely affected in these syndromes. Mechanistically, either aberrant expression of progerin or loss of WRN protein in MSCs alters heterochromatin structure, resulting in premature senescence and exhaustion of functional MSCs in premature aging syndromes. Surprisingly, vascular cells and MSCs in elderly healthy individuals have shown progerin expression and decreased expression levels of WRN, respectively. Studying these rare genetic disorders could thus provide valuable insights into age-related vascular diseases that occur in the general population.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据