Association of Leukocyte Telomere Length and Mitochondrial DNA Copy Number in Children from Salamanca, Mexico

Alegría-Torres, Jorge Alejandro; Velazquez-Villafaña, Marion; López-Gutiérrez, Juan Manuel; Chagoyán-Martínez, Marcela M; Rocha-Amador, Diana Olivia; Costilla-Salazar, Rogelio; García-Torres, Lizeth

doi:10.1089/gtmb.2016.0176

Cited by 17 publications

(11 citation statements)

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“…Moreover, it has been demonstrated that LTL and mtDNA copy number are correlated in intestinal gastric cancer [ 32 ]. Recently, an association between mitochondrial dysfunction and telomere length attrition has been suggested, and a correlation between LTL and mtDNA has been observed by several authors [ 24 , 31 , 60 ]. Both telomere length and mitochondrial function have been proposed as markers of aging (although the evidence is much stronger for telomeres).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA copy number variation, leukocyte telomere length, and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

et al. 2018

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BackgroundLeukocyte telomere length (LTL) and mitochondrial genome (mtDNA) copy number and deletions have been proposed as risk markers for various cancer types, including breast cancer (BC).MethodsTo gain a more comprehensive picture on how these markers can modulate BC risk, alone or in conjunction, we performed simultaneous measurements of LTL and mtDNA copy number in up to 570 BC cases and 538 controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. As a first step, we measured LTL and mtDNA copy number in 96 individuals for which a blood sample had been collected twice with an interval of 15 years.ResultsAccording to the intraclass correlation (ICC), we found very good stability over the time period for both measurements, with ICCs of 0.63 for LTL and 0.60 for mtDNA copy number. In the analysis of the entire study sample, we observed that longer LTL was strongly associated with increased risk of BC (OR 2.71, 95% CI 1.58–4.65, p = 3.07 × 10− 4 for highest vs. lowest quartile; OR 3.20, 95% CI 1.57–6.55, p = 1.41 × 10− 3 as a continuous variable). We did not find any association between mtDNA copy number and BC risk; however, when considering only the functional copies, we observed an increased risk of developing estrogen receptor-positive BC (OR 2.47, 95% CI 1.05–5.80, p = 0.04 for highest vs. lowest quartile).ConclusionsWe observed a very good correlation between the markers over a period of 15 years. We confirm a role of LTL in BC carcinogenesis and suggest an effect of mtDNA copy number on BC risk.Electronic supplementary materialThe online version of this article (10.1186/s13058-018-0955-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA copy number variation, leukocyte telomere length, and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

et al. 2018

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“…Moreover, they seem to (at least indirectly) interact with each other, although supposedly representing distinct biological mechanisms of aging. In fact, previous studies have reported mostly negative correlations between telomere length and epigenetic aging acceleration in different populations, as well as significant positive correlations between telomere length and mtDNA copy number . The study of these markers and how they associate with each other in postmortem brain samples may provide insights into biological aging mechanisms directly relevant for the cognitive and neuroanatomical alterations seen in BD patients, and may also contribute to a better understanding of the complex cross‐talk between blood and brain.…”

Section: Introductionmentioning

confidence: 97%

Accelerated hippocampal biological aging in bipolar disorder

et al. 2019

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Objectives Evidence suggests accelerated aging mechanisms in bipolar disorder (BD), including DNA methylation (DNAm) aging in blood. However, it is unknown whether such mechanisms are also evident in the brain, in particular in association with other biological clocks. To investigate this, we interrogated genome‐wide DNAm in postmortem hippocampus from 32 BD‐I patients and 32 non‐psychiatric controls group‐matched for age and sex from the NIMH Human Brain Collection Core. Methods DNAm age and epigenetic aging acceleration were estimated using the Horvath method. Telomere length (TL) and mitochondrial DNA (mtDNA) copy number were quantified by real‐time PCR. Between‐group differences were assessed by linear regression and univariate general linear models with age, sex, race, postmortem interval, tissue pH, smoking, and body mass index included as co‐variates. Results Groups did not differ for epigenetic aging acceleration when considering the entire sample. However, after splitting the sample by the median age, an epigenetic aging acceleration was detected in patients compared to controls among older subjects (P = .042). While TL did not differ between groups, a reduction in mtDNA copy number was observed in patients compared to controls (P = .047). In addition, significant correlations were observed between epigenetic aging acceleration and TL (r = −.337, P = .006), as well as between TL and mtDNA copy number (r = .274, P = .028). Conclusions Hippocampal aging may underlie neurocognitive dysfunctions observed in BD patients. Moreover, our results suggest a complex cross‐talk between biological clocks in hippocampus that may underlie clinical manifestations of premature aging in BD.

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“…Of the 15 cross-sectional estimates, 7 reported on neonatal adiposity: 4 used binary exposures of small- vs. appropriate-for-gestational age (or appropriate- and large-for-gestational age) 29 – 32 , and 3 studied birth weight continuously 33 – 35 . Eight papers studied childhood adiposity (age range 2–17 years), of which 5 estimates were from studies of overweight/obese vs. non-obese children 12 – 15 , 25 , and 3 were studies of body mass index as a continuous measure 16 – 18 . Longitudinal studies assessed neonatal adiposity, and telomere length after a follow-up (range: ~23–69 years) 21 , 36 – 38 : two studied small- versus appropriate-for-gestational age neonates 36 , 37 , and two studied birth weight as a continuous exposure 21 , 38 .…”

Section: Resultsmentioning

confidence: 99%

Early life adiposity and telomere length across the life course: a systematic review and meta-analysis

Guyatt

Rodriguez²,

Gaunt³

et al. 2018

Wellcome Open Res

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Background: The relationship between adiposity at birth and in childhood, and telomere length is yet to be determined. We aimed to systematically review and meta-analyse the results of studies assessing associations between neonatal and later childhood adiposity, and telomere length. Methods: We searched Medline, EMBASE and PubMed for studies reporting associations between adiposity measured in the neonatal period or later childhood/adolescence, and leucocyte telomere length, measured at any age via quantitative polymerase chain reaction, or terminal restriction fragment analysis, either cross-sectionally, or longitudinally. Papers published before April 2017 were included. Results: Out of 230 abstracts assessed, 23 papers (32 estimates) were retained, from which 19 estimates were meta-analysed (15 cross-sectional, four longitudinal). Of the 15 cross-sectional estimates, seven reported on neonates: four used binary exposures of small-for-gestational-age vs. appropriate-for-gestational age (or appropriate- and large-for-gestational age), and three studied birth weight continuously. Eight estimates reported on later childhood or adolescent measures; five estimates were from studies of binary exposures (overweight/obese vs. non-obese children), and three studies used continuous measures of body mass index. All four longitudinal estimates were of neonatal adiposity, with two estimates for small-for-gestational-age vs. appropriate-for-gestational age neonates, and two estimates of birth weight studied continuously, in relation to adult telomere (49-61 years). There was no strong evidence of an association between neonatal or later childhood/adolescent adiposity, and telomere length. However, between study heterogeneity was high, and there were few combinable studies. Conclusions: Our systematic review and meta-analysis found no strong evidence of an association between neonatal or later childhood or adolescent adiposity and telomere length.

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Association of Leukocyte Telomere Length and Mitochondrial DNA Copy Number in Children from Salamanca, Mexico

Abstract: A strong positive correlation between TL and mtDNAcn was found in the study population; age, sex, and BMI seemed to have no effect on this correlation.

Cited by 17 publications

References 46 publications

Mitochondrial DNA copy number variation, leukocyte telomere length, and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Mitochondrial DNA copy number variation, leukocyte telomere length, and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Accelerated hippocampal biological aging in bipolar disorder

Early life adiposity and telomere length across the life course: a systematic review and meta-analysis

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