Age dependent aneuploidy and telomere length of the human vascular endothelium

Aviv, Hana; Khan, M Yusuf; Skurnick, Joan; Okuda, Koji; Kimura, Masayuki; Gardner, Jeff; Priolo, Lisa; Aviv, Abraham

doi:10.1016/s0021-9150(01)00506-8

Cited by 130 publications

(74 citation statements)

References 24 publications

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“…This could be the consequence of endothelial vascular senescence due to telomere shortening, previously proposed as a mechanism of age‐associated endothelial dysfunction (Erusalimsky, 2009). Indeed, aging has also been shown to result in telomere shortening in the endothelium (Aviv et al ., 2001). In general, brain aging and AD have been shown to be accompanied by a decrease in microvessel density and cerebral blood flow (Brown & Thore, 2011).…”

Section: Discussionmentioning

confidence: 99%

Enhanced microglial pro‐inflammatory response to lipopolysaccharide correlates with brain infiltration and blood–brain barrier dysregulation in a mouse model of telomere shortening

et al. 2015

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SummaryMicroglia are a proliferative population of resident brain macrophages that under physiological conditions self‐renew independent of hematopoiesis. Microglia are innate immune cells actively surveying the brain and are the earliest responders to injury. During aging, microglia elicit an enhanced innate immune response also referred to as ‘priming’. To date, it remains unknown whether telomere shortening affects the proliferative capacity and induces priming of microglia. We addressed this issue using early (first‐generation G1 mTerc−/−)‐ and late‐generation (third‐generation G3 and G4 mTerc−/−) telomerase‐deficient mice, which carry a homozygous deletion for the telomerase RNA component gene (mTerc). Late‐generation mTerc−/− microglia show telomere shortening and decreased proliferation efficiency. Under physiological conditions, gene expression and functionality of G3 mTerc−/− microglia are comparable with microglia derived from G1 mTerc−/− mice despite changes in morphology. However, after intraperitoneal injection of bacterial lipopolysaccharide (LPS), G3 mTerc−/− microglia mice show an enhanced pro‐inflammatory response. Nevertheless, this enhanced inflammatory response was not accompanied by an increased expression of genes known to be associated with age‐associated microglia priming. The increased inflammatory response in microglia correlates closely with increased peripheral inflammation, a loss of blood–brain barrier integrity, and infiltration of immune cells in the brain parenchyma in this mouse model of telomere shortening.

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Section: Discussionmentioning

confidence: 99%

Enhanced microglial pro‐inflammatory response to lipopolysaccharide correlates with brain infiltration and blood–brain barrier dysregulation in a mouse model of telomere shortening

et al. 2015

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“…Telomere length has been shown to be inversely associated with chronological age in endothelial cells from human abdominal aorta, iliac arteries, and iliac veins. 15,16 The impact of telomere-induced vascular senescence may be accentuated in older individuals, in whom recent studies indicate that the number 17 and activity 18 of endothelial progenitor cells is reduced, suggesting an age-associated diminution in regenerative capacity, which may contribute to the age-associated impairment in angiogenesis. 19 …”

Section: Arterial Aging In Apparently Healthy Humansmentioning

confidence: 99%

Arterial Aging

2005

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Abstract-Age is the dominant risk factor for cardiovascular diseases. However, until recently, convincing mechanistic or molecular explanations for the increased cardiovascular risks conferred by aging have been elusive. Aging is associated with alterations in a number of structural and functional properties of large arteries, including diameter, wall thickness, wall stiffness, and endothelial function. Emerging evidence indicates that these age-associated changes are also accelerated in the presence of cardiovascular diseases, and that these changes are themselves risk factors for the appearance or progression of these diseases. In this review, the evidence demonstrating that arterial aging is accelerated in cardiovascular diseases and that accelerated arterial aging is a risk factor for adverse cardiovascular outcomes is briefly reviewed, and selected advances in vascular biology that provide insights into the mechanisms that may underlie the increased risks conferred by arterial aging are summarized. Remarkably, a host of biochemical, enzymatic, and cellular alterations that are operative in accelerated arterial aging have also been implicated in the pathogenesis and progression of arterial diseases. These vascular alterations are thus putative candidates that could be targeted by interventions aimed at attenuating arterial aging, similar to the lifestyle and pharmacological interventions that have already been proven effective. Therefore, the notion that aging is a chronological process and that its risky components cannot be modulated is no longer tenable. It is our hope that a greater appreciation of the links between arterial aging and cardiovascular diseases will stimulate further investigation into strategies aimed at preventing or retarding arterial aging.

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“…43,44 ECs from human abdominal aorta display age-dependent telomere shortening and increased frequency of aneuploidy. 51 A greater rate of telomere attrition has been estimated in human ECs from iliac arteries compared with iliac veins (102 versus 47 bp per year, respectively), and age-dependent intimal telomere loss is greater in the iliac artery versus the internal thoracic artery (147 versus 87 bp per year, respectively), 52 a vessel subjected to less hemodynamic stress. Similarly, Okuda et al 53 reported a higher rate of age-dependent telomere attrition in both the intima and media of the distal versus proximal human abdominal aorta.…”

Section: Telomeres and Atherosclerosismentioning

confidence: 99%

Telomeres and Cardiovascular Disease

Serrano

Andrés

2004

Circulation Research

184

153

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Abstract-Telomeres-the specialized DNA-protein structures at the ends of eukaryotic chromosomes-are essential for maintaining genome stability and integrity and for extended proliferative life span in both cultured cells and in the whole organism. Telomerase and additional telomere-associated proteins are necessary for preserving telomeric DNA length. Age-dependent telomere shortening in most somatic cells, including vascular endothelial cells, smooth muscle cells, and cardiomyocytes, is thought to impair cellular function and viability of the aged organism. Telomere dysfunction is emerging as an important factor in the pathogenesis of hypertension, atherosclerosis, and heart failure. In this Review, we discuss present studies on telomeres and telomere-associated proteins in cardiovascular pathobiology and their implications for therapeutics.

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Age dependent aneuploidy and telomere length of the human vascular endothelium

Cited by 130 publications

References 24 publications

Enhanced microglial pro‐inflammatory response to lipopolysaccharide correlates with brain infiltration and blood–brain barrier dysregulation in a mouse model of telomere shortening

Enhanced microglial pro‐inflammatory response to lipopolysaccharide correlates with brain infiltration and blood–brain barrier dysregulation in a mouse model of telomere shortening

Arterial Aging

Telomeres and Cardiovascular Disease

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