Telomeres, Atherosclerosis, and Human Longevity A Causal Hypothesis
Telomeres, Atherosclerosis, and Human Longevity A Causal Hypothesis
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DOI：
10.1097/ede.0000000000000280
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发表时间：
2015-05-01
期刊：
影响因子：
5.4
通讯作者：
Susser, Ezra
中科院分区：
文献类型：
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作者：
Aviv, Abraham;Kark, Jeremy D.;Susser, Ezra
Aviv et al Epidemiology· Volume 26，Number 3，May 2015 296| www.好吧© 2015 Wolters Kluwer Health，Inc. All rights reserved.应激增加了所有体细胞每次复制的端粒重复序列的丢失。然而，在造血干细胞（HsCs）中，不仅氧化应激而且炎症也会增加端粒缩短，因为HsCs进行更多的复制以取代炎症反应消耗的白细胞。因此，反映HsC端粒长度的较短的白细胞端粒长度28，29归因于由于氧化应激和炎症的较高累积负担（这两种生物学过程被认为是动脉粥样硬化和衰老的标志）而导致的HsC端粒长度损耗较快。白细胞端粒长度作为衰老生物标志物的概念需要这样一个前提，即在出生时，如果不是在受孕时，所有个体的生物年龄-端粒时钟时间-为零。然而，在新生儿中，我们看到白细胞端粒长度的变化很大，其值在8至11 kb或更大的范围内。30，31新生儿中的这种变化超过了整个成人生命过程（20-90年）中估计为<2.0kb的总平均白细胞端粒长度缩短，假设平均白细胞端粒长度损耗率为25-30 bp/年。因此，使用白细胞端粒长度作为体内衰老的生物标志物不仅应考虑白细胞端粒长度损耗，而且还应考虑每个个体出生时的白细胞端粒长度，这是一个经常被忽视的重要问题。
Aviv et al Epidemiology• Volume 26, Number 3, May 2015296| www. epidem. com© 2015 Wolters Kluwer Health, Inc. All rights reserved. stress augments the loss of telomere repeats per replication of all somatic cells. However, in hematopoietic stem cells (HsCs) not only oxidative stress but also inflammation increases telomere shortening, because HsCs undergo more replication to replace leukocytes consumed by the inflammatory response. shorter leukocyte telomere length, which reflects HsC telomere length, 28, 29 has therefore been attributed to a faster HsC telomere-length attrition due to a higher cumulative burden of oxidative stress and inflammation—two biological processes that are considered the hallmarks of atherosclerosis and aging. 22 the concept of leukocyte telomere length as a biomarker of aging entails the premise that at birth, if not at conception, all individuals have a biological age—a telomeric clock time—of zero. in newborns, however, we see great variation in leukocyte telomere length, with values ranging from 8 to 11 kb or more. 30, 31 this variation among newborns exceeds the total average leukocyte telomere length shortening throughout the adult life course (20–90 years) estimated at< 2.0 kb, assuming an average leukocyte telomere length attrition rate of 25–30 bp/year. 32 thus, the use of leukocyte telomere length as a biomarker of aging in vivo should account for not only leukocyte telomere length attrition but also leukocyte telomere length at birth for each individual, an important point often overlooked.