Telomere Length and the Clinical Phenotype of Frailty in Older Adults Undergoing Cardiac Surgery

Brault, Marie Eve; Ohayon, Samuel M.; Kwan, Ricky; Bergman, Howard; Eisenberg, Mark J.; Boivin, Jean‐François; Morin, Jean‐François; Langlois, Yves; Autexier, Chantal; Afilalo, Jonathan

doi:10.1111/jgs.13076

Cited by 13 publications

(7 citation statements)

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“…Recently Werner and colleagues found that specific exercise modalities were associated with increased telomere length and telomerase activity [33].This raises the interesting possibility that the benefits of exercise in reducing and preventing frailty in the older population may act through regulating cellular senescence. The current study found no association between telomere length and frailty, which is consistent with the results demonstrated by Brault et al in older adults with cardiac disease [34]. These results suggest that frailty may be the consequence of repeated physiological stress induced premature cellular senescence in addition to progressive telomere shortening.…”

Section: Telomere Length Telomerase Activity and Adverse Outcomessupporting

confidence: 92%

The association of telomere length and telomerase activity with adverse outcomes in older patients with non-ST-elevation acute coronary syndrome

et al. 2020

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Background Non-ST elevation acute coronary syndrome (NSTEACS) occurs more frequently in older patients with an increased occurrence of recurrent cardiac events following the index presentation. Telomeres are structures consisting of repeated DNA sequences as associated shelterin proteins at the ends of chromosomes. We aim to determine whether telomere length (TL) and telomerase activity (TA) predicted poor outcomes in older patients presenting with NSTEACS undergoing invasive care. Method Older patients undergoing invasive management for NSTEACS were recruited to the ICON-1 biomarker study (NCT01933581). Peripheral blood mononuclear cells (PBMC) were recovered on 153 patients. DNA was isolated and mean TL was measured by quantitative PCR expressed as relative T (telomere repeat copy number) to S (single copy gene number) ratio (T/S ratio), and a telomere repeat amplification assay was used to assess TA during index presentation with NSTEACS. Primary clinical outcomes consisted of death, myocardial infarction (MI), unplanned revascularisation, stroke and significant bleeding recorded at 1 year. TL and TA were divided into tertile groups for analysis. Cox proportional hazards regression was performed. Ordinal regression was performed to evaluate the relationship between TL and TA and traditional cardiovascular risk factors at baseline. Results 298 patients were recruited in the ICON-1 study of which 153 had PBMC recovered. The mean age was 81.0 ± 4.0 years (64% male). Mean telomere length T/S ratio was 0.47 ±

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Section: Telomere Length Telomerase Activity and Adverse Outcomessupporting

confidence: 92%

The association of telomere length and telomerase activity with adverse outcomes in older patients with non-ST-elevation acute coronary syndrome

et al. 2020

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“…Human studies identify several potential mechanisms for frailty including immune dysfunction, oxidative stress in metabolism, and shortening of telomeres (Clegg et al, 2013 ;Zaslavsky et al, 2013 ). Although human telomere length on its own does not correlate well with frailty (Brault et al, 2014 ;Collerton et al, 2012 ;Saum et al, 2014 ); Woo et al, 2008 ), telomere length combined with other biomarkers complements the clinical FI in predicting risk of death (Mitnitski et al, 2015 ).…”

Section: Biology Of Frailtymentioning

confidence: 99%

Screening for Frailty in Canada’s Health Care System: A Time for Action

et al. 2016

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RÉSUMÉAvec le vieillissement de la population canadienne, la fragilité -avec son risque accru du déclin fonctionnel, la détérioration de la santé, et le décès -devient de plus en plus répandue. La physiologie de la fragilité refl ète son origine parmi organes et systèmes multiples. Environ un quart des Canadiens qui sont âgés de plus de 65 sont fragiles, augmentant à plus de la moitié de ceux âgés de plus de 85. Notre système de soins de santé est organisé pour gérer les systèmes mono-organes, ce qui nuit à notre capacité à traiter effi cacement les personnes atteintes de troubles multiples et des limitations fonctionnelles. Pour faire face à la fragilité, il faut reconnaître quand elle se produit, accroître la sensibilisation à son importance, développer des modèles holistiques pour ses soins, et générer des meilleures preuves pour son traitement. La reconnaissance de la façon dont la fragilité impacte la durée de vie permettrait l'intégration des objectifs en matière de soins dans les options de traitement. Les différents organisations de soins responsables variées dans le système de soins de santé canadien nécessiteront des stratégies et outils différentes pour évaluer la fragilité. Les changements dans la politique sera essentiels, étant donné la portée et la complexité des défi s que pose la fragilité au système de soins de santé comme cela est organisé actuellement. ABSTRACTAs Canada's population ages, frailty -with its increased risk of functional decline, deterioration in health status, and death -will become increasingly common. The physiology of frailty refl ects its multisystem, multi-organ origins. About a quarter of Canadians over age 65 are frail, increasing to over half in those older than 85. Our health care system is organized around single-organ systems, impairing our ability to effectively treat people having multiple disorders and functional limitations. To address frailty, we must recognize when it occurs, increase awareness of its signifi cance, develop holistic models of care, and generate better evidence for its treatment. Recognizing how frailty impacts lifespan will allow for integration of care goals into treatment options. Different settings in the Canadian health care system will require different strategies and tools to assess frailty. Given the magnitude of challenges frailty poses for the health care system as currently organized, policy changes will be essential.

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“…Nevertheless, all the studies reviewed here failed in finding an association between frailty and TL shortening: Collerton et al (2012), using both Fried's criteria and FI (40 deficits; n = 552), Marzetti et al (2014) (n = 142) and Yu et al (2015Yu et al ( ) (n = 2006 employing the Fried's criteria, Saum et al (2014) (n = 3537) and Woo et al (2008Woo et al ( ) (n = 2006 using the FI (34 and 17 deficits, respectively). Lack of association between TL and frailty (Fried's criteria) was also obtained by Brault et al (2014) in older subjects with cardiovascular disease (n = 53); however, in this case, they found an unexpected association between longer leukocyte and aortic T/S ratio(mean telomere repeat copy to single gene copy number) and greater number of clinical frailty criteria. Together with these studies, Breitling et al (2016) evaluated the possible association between TL and DNA methylation age acceleration (methylation age minus chronological age) in a population of 851 older adults.…”

Section: Genomic Instabilitymentioning

confidence: 64%

Oxidative stress, genomic features and DNA repair in frail elderly: A systematic review

Sánchez-Flores

Marcos-Pérez

Costa

et al. 2017

Ageing Research Reviews

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Frailty is an emerging geriatric syndrome characterized by higher vulnerability to stressors, with an increased risk of adverse health outcomes such as mortality, morbidity, disability, hospitalization, and institutionalization. Although it is generally recognized to have a biological basis, no particular biological trait has been consistently associated to frailty status so far. In this work, epidemiological studies evaluating association of frailty status with alterations at cellular level - namely oxidative stress, genomic instability and DNA damage and repair biomarkers -were revised and compared. A total of 25 studies fulfilled inclusion/exclusion criteria and, consequently, were included in the review. Variations of oxidative stress biomarkers were often associated to frailty status in older people. On the contrary, genomic instability seems not to be linked to frailty. The only study which addressed the possible relationship between DNA repair modulations and frailty status also failed in finding association. Despite the large number of cellular alterations known to be associated with frailty, studies on this issue are still very scarce and limited to some of the possible cellular targets. The established link between DNA repair, genomic instability, and age and age-related disorders, encourage deeper investigations on this line.

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Telomere Length and the Clinical Phenotype of Frailty in Older Adults Undergoing Cardiac Surgery

Cited by 13 publications

References 10 publications

The association of telomere length and telomerase activity with adverse outcomes in older patients with non-ST-elevation acute coronary syndrome

The association of telomere length and telomerase activity with adverse outcomes in older patients with non-ST-elevation acute coronary syndrome

Screening for Frailty in Canada’s Health Care System: A Time for Action

Oxidative stress, genomic features and DNA repair in frail elderly: A systematic review

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