Short Leukocyte Telomere Length Precedes Clinical Expression of Atherosclerosis

Bénétos, Athanase; Toupance, Simon; Gautier, Sylvie; Labat, Carlos; Kimura, Masayuki; Rossi, P.; Settembre, Nicla; Hubert, Jacques; Frimat, Luc; Bertrand, B.; Boufi, Mourad; Flecher, Xavier; Sadoul, Nicolas; Eschwège, P.; Kessler, Michèle; Tzanetakou, Irene P.; Doulamis, Ilias P.; Konstantopoulos, Panagiotis; Tzani, Aspasia; Korou, Marilina; Gkogkos, Anastasios; Perreas, Konstantinos; Menenakos, Evangelos; Samanidis, George; Vasiloglou‐Gkanis, Michail; Kark, Jeremy D.; Malikov, Sergueï; Verhulst, Simon; Aviv, Abraham

doi:10.1161/circresaha.117.311751

Cited by 76 publications

(68 citation statements)

References 24 publications

(25 reference statements)

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“…In some cases, this is supported by longitudinal evidence (e.g. [45,48,49]) and Mendelian randomization studies [50,51]. Reverse causality may be possible for psychological and behavioural variables too, because short telomere length can change patterns of gene expression [52], with possible consequences for brain function.…”

Section: Discussionmentioning

confidence: 99%

Telomeres as integrative markers of exposure to stress and adversity: a systematic review and meta-analysis

Pepper¹,

Bateson²,

Nettle³

2018

R. Soc. open sci.

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Telomeres have been proposed as a biomarker that integrates the impacts of different kinds of stress and adversity into a common currency. There has as yet been no overall comparison of how different classes of exposure associate with telomeres. We present a meta-analysis of the literature relating telomere measures to stresses and adversities in humans. The analysed dataset contained 543 associations from 138 studies involving 402 116 people. Overall, there was a weak association between telomere variables and exposures (greater adversity, shorter telomeres: r = −0.15, 95% CI −0.18 to −0.11). This was not driven by any one type of exposure, because significant associations were found separately for physical diseases, environmental hazards, nutrition, psychiatric illness, smoking, physical activity, psychosocial and socioeconomic exposures. Methodological features of the studies did not explain any substantial proportion of the heterogeneity in association strength. There was, however, evidence consistent with publication bias, with unexpectedly strong negative associations reported by studies with small samples. Restricting analysis to sample sizes greater than 100 attenuated the overall association substantially (r = −0.09, 95% CI −0.13 to −0.05). Most studies were underpowered to detect the typical association magnitude. The literature is dominated by cross-sectional and correlational studies which makes causal interpretation problematic.

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Section: Discussionmentioning

confidence: 99%

Telomeres as integrative markers of exposure to stress and adversity: a systematic review and meta-analysis

Pepper¹,

Bateson²,

Nettle³

2018

R. Soc. open sci.

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“…Telomere attrition was 9.8 bp day −1 (table 2, [37]; jackdaws Corvus monedula: 10.5 bp d −1 [9,22]). The rate of telomere loss appears to be higher at the higher percentiles (electronic supplementary material, table S1; figure 3a), also in accordance with findings in jackdaws [22] and common terns [38].…”

Section: Discussionmentioning

confidence: 97%

“…Also, on the level of the whole organism, there is an association between lifespan/annual survival and TL and its attrition [3][4][5][6][7][8]. There is accumulating evidence that telomere attrition during development is of particular importance for later health and survival [9,10]. Different external factors could affect telomere attrition, but it is generally assumed that most of these exert their effect through oxidative stress [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Antioxidant supplementation slows telomere shortening in free-living white stork chicks

et al. 2020

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Telomere length (TL) and shortening is increasingly shown to predict variation in survival and lifespan, raising the question of what causes variation in these traits. Oxidative stress is well known to accelerate telomere attrition in vitro, but its importance in vivo is largely hypothetical. We tested this hypothesis experimentally by supplementing white stork (Ciconia ciconia) chicks with antioxidants. Individuals received either a control treatment, or a supply of tocopherol (vitamin E) and selenium, which both have antioxidant properties. The antioxidant treatment increased the concentration of tocopherol for up to two weeks after treatment but did not affect growth. Using the telomere restriction fragment technique, we evaluated erythrocyte TL and its dynamics. Telomeres shortened significantly over the 21 days between the baseline and final sample, independent of sex, mass, size and hatching order. The antioxidant treatment significantly mitigated shortening rate of average TL (−31% in shorter telomeres; percentiles 10th, 20th and 30th). Thus, our results support the hypothesis that oxidative stress shortens telomeres in vivo.

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“…On the other hand, many findings support the idea that short LTL precedes by several decades the clinical manifestations of ASCVD and related metabolic risks (Codd et al 2013;Chen et al 2014;Zhao et al 2014;Scheller Madrid et al 2016;Verhulst et al 2016). Consequently, LTL, may be an active determinant in the development of the disease later in life, and hence plays a role in causal pathways rather than being exclusively a risk marker for ASCVD (Toupance et al 2017;Shabharwal et al 2018;Benetos et al 2018). Such outcomes raise the question of whether the associations of LTL D r a f t with the diseases cited above reflect: 1) an inter-individual LTL variation already apparent since development; 2) a variation in the rate of age-dependent LTL attrition afterward, or 3) both (Shabharwal et al 2018).…”

Section: Introductionmentioning

confidence: 88%

Telomere length and age-dependent telomere attrition: the blood-and-muscle model

Chahine

Toupance

El-Hakim

et al. 2019

Can. J. Physiol. Pharmacol.

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Short telomere length (TL) is associated with atherosclerotic cardiovascular disease (ACVD) and other age-related diseases. It is unclear whether these associations originate from having inherently short TL or a faster TL attrition before or during disease development. We proposed the blood-and-muscle model to assess TL dynamics throughout life course. Our objective was to measure TL in leukocytes (LTL) and in skeletal muscle (MTL), which served as a proxy of TL at birth. The delta (MTL–LTL) represented life-long telomere attrition. Blood draws and skeletal muscle biopsies were performed on 35 Lebanese individuals undergoing surgery. Following DNA extraction, LTL and MTL were measured by Southern blot. In every individual aged between 30 and 85 years, MTL was longer than LTL. With age, MTL and LTL decreased, but the delta (MTL–LTL) increased by 14 bp/year. We validated the blood-and-muscle model that allowed us to identify TL, TL at birth, and lifelong TL attrition in a cross-sectional study. This model can be used in larger cross-sectional studies to evaluate the association of telomere dynamics with age-related diseases onset and progression.

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Short Leukocyte Telomere Length Precedes Clinical Expression of Atherosclerosis

Abstract: Supplemental Digital Content is available in the text.

Cited by 76 publications

References 24 publications

Telomeres as integrative markers of exposure to stress and adversity: a systematic review and meta-analysis

Telomeres as integrative markers of exposure to stress and adversity: a systematic review and meta-analysis

Antioxidant supplementation slows telomere shortening in free-living white stork chicks

Telomere length and age-dependent telomere attrition: the blood-and-muscle model

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