Telomere G-tail Length is a Promising Biomarker Related to White Matter Lesions and Endothelial Dysfunction in Patients With Cardiovascular Risk: A Cross-sectional Study

Nezu, Tomohisa; Hosomi, Naohisa; Anno, Kumiko; Aoki, Shiro; Shimamoto, Akira; Makino, Hírofumi; Hayashi, Tomonori; Matsumoto, Masayasu; Tahara, Hidetoshi

doi:10.1016/j.ebiom.2015.05.025

Cited by 15 publications

(21 citation statements)

References 30 publications

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“…Additional protein-protein interactions mediate the communication of telomeres with structural components of the cell nucleus (16). Because of its crucial role in chromosome protection, it has been recently suggested that shorter G-tail length is more directly associated with age and higher disease risk factors than total telomere length (TL) (17), suggesting G-tail as a new potential biomarker, alternative to TL per se (18). Besides shelterin, G-quadruplexes are other higher-order structures, protecting the 3' overhang of telomeres from being accessed by the enzyme telomerase (19).…”

Section: Telomere-binding Proteinsmentioning

confidence: 99%

“…A lot of effort has been done to evaluate whether clinical practice could benefit from TL measurement; © 1996-2018 Recent discoveries showed that DNA can be damaged also with normal TL, if G-tail structure is disrupted, suggesting, that G-tail length contributes more to pathologies than TL itself (18). It has been associated with age and vascular risk factors (17) and methods for the examination of G-tail length with a high-throughput platform using genomic DNA or cell lysate are faster than classical methods for TL determination, giving G-tail priority as a biomarker choice in the future studies (127).…”

Section: Telomeres As a Biomarkermentioning

confidence: 99%

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The future of telomere length in personalized medicine

Visvikis‐Siest¹

2018

Front Biosci

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Telomere length has been subject of studies for many decades, aiming to elucidate its role in physiological processes, in process of aging and in diverse pathologies. Yet today, there is still no "big title" discovery that would lead to a practical use of telomeres as a reliable biomarker or target for a new drug. However, therapies for chronic disease patients are being tested and companies are already offering commercial tests for telomere length measurement. The strong genetic heritability of telomeres is opening the place for pharmacogenomics researches that could promote the personalized treatment of diverse diseases. In this article, we present the recent knowledge of telomeres genetic determination obtained by genome-wide association studies (GWAS), important biomarkers related to telomere length and review the possibilities of telomere's practical implementation in the medical treatment of diverse diseases and as a potential biomarker in personalized medicine. Furthermore, we summarise commercial offers of telomere length measurements available and we discuss the actions that should be taken to make steps forward into final application of the accumulated knowledge into practical use.

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Section: Telomere-binding Proteinsmentioning

confidence: 99%

Section: Telomeres As a Biomarkermentioning

confidence: 99%

The future of telomere length in personalized medicine

Visvikis‐Siest¹

2018

Front Biosci

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“…According to the general theory, telomere length is inversely correlated with age. In addition, it has been reported that the telomeric 3’-overhang (G-tail) length is associated with a risk of cardiovascular events [5, 6]. However, the significance of telomere/G-tail length in LT has not been well studied.…”

Section: Introductionmentioning

confidence: 99%

Influence of donor liver telomere and G-tail on clinical outcome after living donor liver transplantation

et al. 2019

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It has been reported that donor age affects patient outcomes after liver transplantation, and that telomere length is associated with age. However, to our knowledge, the impact of donor age and donor liver telomere length in liver transplantation has not been well investigated. This study aimed to clarify the influence of the length of telomere and G-tail from donor livers on the outcomes of living donors and recipients after living donor liver transplantation. The length of telomere and G-tail derived from blood samples and liver tissues of 55 living donors, measured using the hybridization protection assay. The length of telomeres from blood samples was inversely correlated with ages, whereas G-tail length from blood samples and telomere and G-tail lengths from liver tissues were not correlated with ages. Age, telomere, and G-tail length from blood did not affect postoperative liver failure and early liver regeneration of donors. On the other hand, the longer the liver telomere, the poorer the liver regeneration tended to be, especially with significant difference in donor who underwent right hemihepatectomy. We found that the survival rate of recipients who received liver graft with longer telomeres was inferior to that of those who received liver graft with shorter ones. An elderly donor, longer liver telomere, and higher Model for End-Stage Liver Disease score were identified as independent risk factors for recipient survival after transplantation. In conclusion, telomere shortening in healthy liver does not correlate with age, whereas longer liver telomeres negatively influence donor liver regeneration and recipient survival after living donor liver transplantation. These results can direct future studies and investigations on telomere shortening in the clinical and experimental transplant setting.

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“…According to their observations, G-tail length decreases with age ( Nezu et al, 2015 ). This would be in agreement with previous observations that telomere shortening is accompanied by G-tail shortening.…”

mentioning

confidence: 99%

“…But until recently, whether or not this is the case in the clinical settings has remained elusive. In this issue of EBioMedicine , using a highly sensitive and quantitative method, Nezu, Tahara and colleagues quantitated both G-tail and total telomere length of leukocytes in patients with a history of cerebrovascular disease or atypical neurological problems ( Nezu et al, 2015 ). Cross-sectional analyses revealed that G-tail length, rather than total telomere length, is associated with endothelial function and severity of age-related white matter changes.…”

mentioning

confidence: 99%