期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 315, 期 1, 页码 H1-H5出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00008.2018
关键词
aging; senescence; telomere dysfunction; vascular function
资金
- National Institute on Aging [AG-040297, AG-043952, AG-046326, AG-044339, AG-050238]
- Department of Veterans Affairs [1I01BX002151]
- University of Utah Center on Aging pilot grant
Although most telomere biology research continues to focus on telomere shortening, there is increasing evidence that telomere deprotection, or uncapping, is more biologically and possibly clinically important. Telomeres form t-loops to prevent the chromosome ends from appearing as a double-stranded DNA break and initiating a DNA damage response. Breakdown of the t-loop structure, referred to as uncapping, can lead to cellular senescence, increased oxidative stress, and inflammation in tissues. In this review, we describe how telomere uncapping potentially leads to age-related vascular dysfunction and increased cellular senescence, oxidative stress, and inflammation. Importantly, we present evidence to argue that telomere uncapping is more biologically relevant than telomere shortening and a better marker of vascular aging and target for antiaging interventions.
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