Association of Shorter Leukocyte Telomere Repeat Length With Dementia and Mortality

Honig, Lawrence S.; Kang, Min Suk; Schupf, Nicole; Lee, Joseph H.; Mayeux, Richard

doi:10.1001/archneurol.2012.1541

Cited by 157 publications

(137 citation statements)

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“…Telomere measurements were performed as previously described (Honig et al 2012). Coded DNA samples were processed by laboratory personnel, masked to participant characteristics including dietary information.…”

Section: Telomere Measurementmentioning

confidence: 99%

“…Some cells, such as germline cells, have greater ability to preserve telomere length through the enzymatic activity known as telomerase. Leukocyte telomere length (LTL) has been proposed to be a marker for biological aging, and shortened LTL has been related with higher allcause mortality (Honig et al 2012) as well as a variety of age-related conditions such as cardiovascular disease (Estruch et al 2013;Mainous et al 2010;Perez-Rivera et al 2014), diabetes (Zhao et al 2013), and dementia (Honig et al 2012).…”

Section: Introductionmentioning

confidence: 99%

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Mediterranean diet and leukocyte telomere length in a multi-ethnic elderly population

Honig

Schupf

et al. 2015

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Leukocyte telomere length (LTL) is considered as the marker of biological aging and may be related to environmental factors. The current study aimed to examine the relation between Mediterranean-type diet and LTL. We used a cross-sectional study of 1743 multi-ethnic community residents of New York aged 65 years or older. Mediterranean-type diet (MeDi) was calculated from dietary information collected using a food frequency questionnaire. LTL was measured from leukocyte DNA using a real-time PCR method to measure T/S ratio, the ratio of telomere (T) to single-copy gene (S) sequence. Regression analysis showed that the MeDi score was not associated with LTL in the overall study population (β=12.5; p=0.32) after adjusting for age, sex, education, ethnicity, caloric intake, smoking, and physical and leisure activities. However, we found a significant association between MeDi and LTL among non-Hispanic whites (β=48.3; p=0.05), and the results held after excluding dementia subjects (β= 49.6; p = 0.05). We further found that, in the whole population, vegetable and cereal consumption above the sex-specific population median was associated with longer LTL (β=89.1, p=0.04) and shorter LTL (β = −93.5; p = 0.03), respectively. Among non-Hispanic whites, intake of meat or dairy below sex-specific population medians was associated with longer LTL (β=154.7, p=0.05; β= 240.5, p < 0.001, respectively). We found that higher adherence to a MeDi was associated with longer LTL among whites but not among African Americans and Hispanics. Additionally, a diet high in vegetables but low in cereal, meat, and dairy might be associated with longer LTL among healthy elderly.

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Section: Telomere Measurementmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mediterranean diet and leukocyte telomere length in a multi-ethnic elderly population

Honig

Schupf

et al. 2015

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“…Mutations that decrease telomerase and cause short telomeres in humans lead to a spectrum of premature-onset diseases and conditions collectively termed "telomere syndromes," which share many features of the common diseases of aging in the human population (Armanios and Blackburn 2012). Multiple independent studies have found impaired human telomeric DNA length maintenance to be associated with a wide range of diseases and for several age-related diseases to predict future risks and outcomes including mortality (Von Zglinicki et al 2000;Samani et al 2001;Cawthon et al 2003;Panossian et al 2003;Valdes et al 2005;Bischoff et al 2006;Harris et al 2006;MartinRuiz et al 2006;Bakaysa et al 2007;Brouilette et al 2007;Fitzpatrick et al 2007Fitzpatrick et al , 2011Aubert and Lansdorp 2008;Farzaneh-Far et al 2008;Kimura et al 2008;Epel et al 2009;Njajou et al 2009;Astrup et al 2010;Codd et al 2010Codd et al , 2013Salpea et al 2010;Willeit et al 2010a,b;Zee et al 2010;Strandberg et al 2011;Wentzensen et al 2011;Yaffe et al 2011;Honig et al 2012;Lee et al 2012;Weischer et al 2012;Bojesen 2013;Muezzinler et al 2013;Gardner et al 2014;Haycock et al 2014;Walsh et al 2014).…”

mentioning

confidence: 99%

“…A recent study incorporating data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002, a large, nationally representative, ethnically and socioeconomically diverse sample, reported that sex, race-ethnicity, and socioeconomic status (SES) moderated the associations between TL and mortality in older individuals (Needham et al 2012). However, while some human cohort studies have found shorter PBMC TL or LTL is associated with increased mortality (Cawthon et al 2003;Martin-Ruiz et al 2006;Bakaysa et al 2007;Farzaneh-Far et al 2008;Kimura et al 2008;Epel et al 2009;Astrup et al 2010;Willeit et al 2010b;Fitzpatrick et al 2011;Honig et al 2012;Lee et al 2012;Weischer et al 2012), others have not (Bischoff et al 2006;Harris et al 2006;Njajou et al 2009;Strandberg et al 2011). These inconsistencies in the literature may be due to differences in study cohorts, sample sizes, assay methods, and other methodological differences (Bojesen 2013).…”

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confidence: 99%

Automated Assay of Telomere Length Measurement and Informatics for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort

et al. 2015

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The Kaiser Permanente Research Program on Genes, Environment, and Health (RPGEH) Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort includes DNA specimens extracted from saliva samples of 110,266 individuals. Because of its relationship to aging, telomere length measurement was considered an important biomarker to develop on these subjects. To assay relative telomere length (TL) on this large cohort over a short time period, we created a novel high throughput robotic system for TL analysis and informatics. Samples were run in triplicate, along with control samples, in a randomized design. As part of quality control, we determined the within-sample variability and employed thresholds for the elimination of outlying measurements. Of 106,902 samples assayed, 105,539 (98.7%) passed all quality control (QC) measures. As expected, TL in general showed a decline with age and a sex difference. While telomeres showed a negative correlation with age up to 75 years, in those older than 75 years, age positively correlated with longer telomeres, indicative of an association of longer telomeres with more years of survival in those older than 75. Furthermore, while females in general had longer telomeres than males, this difference was significant only for those older than age 50. An additional novel finding was that the variance of TL between individuals increased with age. This study establishes reliable assay and analysis methodologies for measurement of TL in large, population-based human studies. The GERA cohort represents the largest currently available such resource, linked to comprehensive electronic health and genotype data for analysis.KEYWORDS relative telomere length; GERA cohort; saliva DNA; robotic assay; quantitative PCR T ELOMERES are the protective DNA-protein complexes that cap the ends of eukaryotic chromosomes and are required for genome stability. The essential telomeric DNA consists of a tract of a tandemly repeated short sequence specified and maintained by the highly regulated reverse transcriptase action of the cellular enzyme telomerase. Telomeric DNA is susceptible to natural terminal erosion through a variety of processes including the end replication problem of linear chromosomal DNA, which causes telomeres to get shorter each time a somatic cell divides (Olovnikov 1973;

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“…Hayflick (HAYFLICK, 1965) (HONIG et al, 2006(HONIG et al, , 2012KOTA et al, 2015), incluindo a doença de Alzheimer (DA) (LIU et al, 2016). …”

Section: Encurtamento Teloméricounclassified

Comprimento telomérico no sistema nervoso central de um modelo de doença de Alzheimer tratado com lítio

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Association of Shorter Leukocyte Telomere Repeat Length With Dementia and Mortality

Cited by 157 publications

References 40 publications

Mediterranean diet and leukocyte telomere length in a multi-ethnic elderly population

Mediterranean diet and leukocyte telomere length in a multi-ethnic elderly population

Automated Assay of Telomere Length Measurement and Informatics for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort

Comprimento telomérico no sistema nervoso central de um modelo de doença de Alzheimer tratado com lítio

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Association of Shorter Leukocyte Telomere Repeat Length With Dementia and Mortality

Cited by 157 publications

References 40 publications

Mediterranean diet and leukocyte telomere length in a multi-ethnic elderly population

Mediterranean diet and leukocyte telomere length in a multi-ethnic elderly population

Automated Assay of Telomere Length Measurement and Informatics for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort

Comprimento telomérico no sistema nervoso central de um modelo de doença de Alzheimer tratado com lí­tio

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Comprimento telomérico no sistema nervoso central de um modelo de doença de Alzheimer tratado com lítio