Telomere Diseases

Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
New England Journal of Medicine (Impact Factor: 54.42). 12/2009; 361(24):2353-65. DOI: 10.1056/NEJMra0903373
Source: PubMed
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Available from: Rodrigo T Calado, Jun 30, 2015
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    ABSTRACT: Telomeres are DNA-protein complexes that cap linear DNA strands, protecting DNA from damage. Recently, shorten telomeres length has been reported in bipolar disorder (BD) and depression. The enzyme telomerase regulates telomeres length, which has been associated with cellular viability; however it is not clear how telomerase may be involved in the pathophysiology and therapeutics of BD. In the present study, leukocyte telomerase activity was assessed in 28 medication-free BD depressed individuals (DSM-IV-TR criteria) at baseline and after 6 weeks of lithium therapy (n=21) also matched with 23 healthy controls. There was no difference between telomerase activity in subjects with BD depression (before or after lithium) and controls. Improvement of depressive symptoms was negatively associated with telomerase activity after 6 weeks of lithium therapy. This is the first study describing telomerase activity in BD research. Overall, telomerase activity seems not directly involved in the pathophysiology of short-term BD. Lithium's antidepressant effects may involve regulation at telomerase activity. Further studies with larger samples and long-term illness are also warranted.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 04/2014; DOI:10.1016/j.euroneuro.2014.03.005 · 5.40 Impact Factor
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    ABSTRACT: What are the relationships between telomere lengths in leukocytes and sperm, sperm count and parents' age at conception in a group of apparently healthy subjects of the same age? Sperm telomere length (STL) is related to sperm count, it is lower in oligozoospermic than in normozoospermic men and it is directly related to parents' age at conception. Leukocyte telomere length (LTL) decreases with age but STL increases and offspring of older fathers tend to have longer leukocyte telomeres. Only one study analyzed STL in relation to male fertility, and reported shorter telomeres in infertile versus fertile men. No data have been reported on STL in relation to parents' age at conception. Prospective study conducted from January to December 2012 of 18-19-year-old high school students. The volunteers were 81 apparently healthy subjects, including 61 with normozoospermia and 20 with idiopathic oligozoospermia. Leukocyte and sperm telomere length were measured by real-time PCR. Data were analyzed for determining the relationships between LTL, STL, sperm count and parents' age at conception. Sperm and leukocyte telomere length were strongly correlated, but STL was significantly longer. A significant positive correlation between STL and total sperm number was found. STL was significantly lower in oligozoospermic than in normozoospermic men. Finally, we found a significant positive relationship between maternal age and both leukocyte and sperm telomere length and a significant positive relation between paternal age and STL in the offspring. The relative contributions of mothers' and fathers' ages to their offspring's telomere length could not be determined because of the high correlation between paternal and maternal ages. Although consistent with previous findings, this is the first study on telomere length in oligo- and normozoospermic men and included a relatively low number of subjects. Our study was also restricted to young (18-19 year old) men, so future studies should determine whether our findings can be generalized to men at ages typically encountered at fertility centers. Future studies should also try to determine the possible effect of abstinence time and frequency of ejaculation with STL. Our study sheds new light on the association between STL and sperm count and on the inheritance of telomere length (in leukocytes and sperm) in relation to the parents' age at conception. Additional studies are needed to confirm these observations, to clarify if the association between shorter STL and damaged spermatogenesis represents a pathophysiological link, and to determine the effect on offspring telomere length of assisted reproduction techniques performed on couples of advanced age or where the man is oligozoospermic. This work was supported by the Italian Ministry of University and Research (grant no. 2009AMPA9C to C.F.) and Padova University (grant 2010 to A.D.R.). The authors have no competing interests to declare.
    Human Reproduction 10/2013; DOI:10.1093/humrep/det392 · 4.59 Impact Factor
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    ABSTRACT: SHORT LEUKOCYTE TELOMERE LENGTH (LTL) IS ASSOCIATED WITH ATHEROSCLEROSIS IN ADULTS AND: diminished survival in the elderly. LTL dynamics are defined by LTL at birth, which is highly variable, and its age dependent attrition thereafter, which is rapid during the first 20 years of life. We examined whether age-dependent LTL attrition during adulthood can substantially affect individuals' LTL ranking (e.g., longer or shorter LTL) in relation to their peers. We measured LTL in samples donated 12 years apart on average by 1156 participants in four longitudinal studies. We observed correlations of 0.91-0.96 between baseline and follow-up LTLs. Ranking individuals by deciles revealed that 94.1% (95%, confidence intervals of 92.6-95.4%) showed no rank change or a 1 decile change over time. We conclude that in adults LTL is virtually anchored to a given rank with the passage of time. Accordingly, the links of LTL with atherosclerosis and longevity appear to be established early in life. It is unlikely that lifestyle and its modification during adulthood exert a major impact on LTL ranking. This article is protected by copyright. All rights reserved.
    Aging cell 04/2013; DOI:10.1111/acel.12086 · 5.94 Impact Factor