Telomeres and Cardiovascular Disease

Serrano, Antonio L.; Andrés, Vicente

doi:10.1161/01.res.0000122141.18795.9c

Cited by 185 publications

(160 citation statements)

References 98 publications

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“…Telomere maintenance has relevance for long-term health. Shortened telomere length and/or reduced telomerase activity have been consistently associated with health risk and diseases (12)(13)(14)(15). Declines in the telomere/telomerase maintenance system may play a causal role in aging, serve as a biomarker of aging, or both.…”

Section: Developmental Programming | Fetal Originmentioning

confidence: 99%

Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood

Entringer

Epel

Kumsta

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

353

244

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Leukocyte telomere length (LTL) is a predictor of age-related disease onset and mortality. The association in adults of psychosocial stress or stress biomarkers with LTL suggests telomere biology may represent a possible underlying mechanism linking stress and health outcomes. It is, however, unknown whether stress exposure in intrauterine life can produce variations in LTL, thereby potentially setting up a long-term trajectory for disease susceptibility. We, therefore, as a first step, tested the hypothesis that stress exposure during intrauterine life is associated with shorter telomeres in adult life after accounting for the effects of other factors on LTL. LTL was assessed in 94 healthy young adults. Forty-five subjects were offspring of mothers who had experienced a severe stressor in the index pregnancy (prenatal stress group; PSG), and 49 subjects were offspring of mothers who had a healthy, uneventful index pregnancy (comparison group; CG). Prenatal stress exposure was a significant predictor of subsequent adult telomere length in the offspring (178-bp difference between prenatal stress and CG; d = 0.41 SD units; P < 0.05). The effect was substantially unchanged after adjusting for potential confounders (subject characteristics, birth weight percentile, and early-life and concurrent stress level), and was more pronounced in women (295-bp difference; d = 0.68 SD units; P < 0.01). To the best of our knowledge, this study provides the first evidence in humans of an association between prenatal stress exposure and subsequent shorter telomere length. This observation may help shed light on an important biological pathway underlying the developmental origins of adult health and disease risk.developmental programming | fetal origin

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Section: Developmental Programming | Fetal Originmentioning

confidence: 99%

Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood

Entringer

Epel

Kumsta

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

353

244

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“…134,135 Inhibition of nuclear TERT activity shortens telomere length, leading to decrease in the endothelial cell's life span, alteration in gene expression and change from phenotype of young cells to phenotype of old cells. 136 In addition, telomere shortening stimulates activation of p53, p21 and p16 proteins, which are triggers of cell senescence. 137,138 The endogenous eNOS inhibitor asymmetrical dimethylarginine also accelerates endothelial cell senescence through increase in production of ROS and inhibition of NO production.…”

Section: Endothelial Cell Senescencementioning

confidence: 99%

Endothelial dysfunction and hypertension in aging

2012

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Hypertension is one of the common diseases in the elderly. The prevalence of hypertension markedly increases with advancing age. Both aging and hypertension have a critical role in cardiovascular and cerebrovascular complications. Although aging and hypertension, either independently or collectively, impair endothelial function, aging and hypertension may have similar cascades for the pathogenesis and development of endothelial dysfunction. Nitric oxide (NO) has an important role in regulation of vascular tone. Decrease in NO bioavailability by endothelial dysfunction would lead to elevation of blood pressure. An imbalance of reduced production of NO or increased production of reactive oxygen species, mainly superoxide, may promote endothelial dysfunction. One possible mechanism by which the prevalence of hypertension is increased in relation to aging may be advancing endothelial dysfunction associated with aging through an increase in oxidative stress. In addition, endothelial cell senescence is also involved in aging-related endothelial dysfunction. In this review, we focus on recent findings and interactions between endothelial function, oxidative stress and hypertension in aging.

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“…TERT-expressing cells show extensive changes in gene expression patterns; the ability of hTERT to exert a variety of effects that counteract cell death is striking (Sung et al, 2005) and these effects have been reported also in whole animals overexpressing TERT; in mice this protects against experimental heart failure ( Oh et al, 2001) and has many other effects in the cardiovascular system (Serrano and Andres, 2004). hTERT-expressing cells are more resistant to chromosome damage caused by ionizing radiation (Pirzio et al, 2004).…”

Section: The Potential Role Of Telomerase In Cell Therapy In Agingmentioning

confidence: 99%

Telomerase and the aging process

Hornsby¹

2007

Experimental Gerontology

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The level of telomerase activity is important in determining telomere length in aging cells and tissues. Here evidence on the importance of telomerase activity is reviewed with respect to aging rates of mammalian species and the health and life span of individuals within a species. The significance of telomerase reactivation for both cancer development and for immortalizing cells for therapeutic processes is assessed. KeywordsTelomerase; telomeres; senescence; cancer; immortalization Telomeres are the specialized repetitive DNA sequences at the ends of the linear chromosomes, and associated proteins, that serve to maintain the integrity of the chromosomes. Telomerase is a ribonucleoprotein DNA polymerase complex that maintains telomere length. The complex comprises the protein telomerase reverse transcriptase (TERT, or hTERT in humans) and a catalytic RNA (TERC) (Shay and Wright, 2007). In the absence of telomerase activity telomeres progressively shorten. Telomerase activity is absent in most normal human somatic cells because of the lack of expression of TERT; TERC is usually present. On the other hand most mouse cells have telomerase activity (Blasco, 2005). Without telomerase, telomere shortening eventually limits the growth of cells, either by senescence, in cells with intact cell cycle checkpoints (a G1 cell cycle block), or by crisis in cells with inactivated checkpoints (telomeric end-to-end fusions cause chromosome breakage and mitotic catastrophe) (Shay and Wright, 2007). Expression of TERT in cells that otherwise lack telomerase activity causes cells to bypass senescence and crisis, and such cells are usually termed "immortalized." The significance of senescence, crisis and immortalization is explored further in this revew (see Figure 1). Do telomere biology and telomerase activity determine aging?The first aspect to this question is whether differences in aging rates among mammalian species are caused in whole or in part by species-specific differences in telomerase/telomere biology. A very brief consideration of this question will show that this is unlikely. Mice are short-lived compared to humans, yet mice have long telomeres and adult mouse somatic cells often have telomerase activity (Blasco, 2005). On the other hand, humans have relatively short telomeres, even when compared to closely related primates (Kakuo et al., 1999), and telomerase activity

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Telomeres and Cardiovascular Disease

Cited by 185 publications

References 98 publications

Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood

Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood

Endothelial dysfunction and hypertension in aging

Telomerase and the aging process

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