Leukocyte telomere length and epigenetic-based mortality risk score: associations with all-cause mortality among older adults

Telomere length (TL) has been established as a biomarker of aging and aging-related health outcomes, but showed only a weak or inconsistent association with all-cause mortality in previous epidemiological studies. Recently, an epigenetic 'mortality risk score' (MS) based on whole blood DNA...

Celý popis

Uložené v:
Podrobná bibliografia
Vydané v:Epigenetics Ročník 13; číslo 8; s. 846 - 857
Hlavní autori: Gao, Xu, Zhang, Yan, Mons, Ute, Brenner, Hermann
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States Taylor & Francis 03.08.2018
Taylor & Francis Group
Predmet:
Aged
aging
DNA Methylation
Epigenesis, Genetic
epigenetic epidemiology
Female
Humans
Leukocytes - metabolism
Longevity - genetics
Male
Middle Aged
Mortality
mortality risk score
Research Paper
Telomere
Telomere Homeostasis
mortality
epigenetic epidemiology
DNA Methylation
mortality risk score
aging
Telomere
ISSN:1559-2294, 1559-2308, 1559-2308
On-line prístup:Získať plný text
Tagy: Pridať tag
Žiadne tagy, Buďte prvý, kto otaguje tento záznam!
Popis
Shrnutí:Telomere length (TL) has been established as a biomarker of aging and aging-related health outcomes, but showed only a weak or inconsistent association with all-cause mortality in previous epidemiological studies. Recently, an epigenetic 'mortality risk score' (MS) based on whole blood DNA methylation at 10 mortality-related CpG sites has been demonstrated to be strongly related to all-cause mortality at the population level. This study aimed to address the association between TL and this MS, and to assess and compare their associations with all-cause mortality. The MS was derived from the DNA methylation profiles measured by Illumina Human Methylation450K Beadchip and TL was measured by quantitative PCR at baseline among 1517 participants aged 50-75 of the German ESTHER cohort study. In cross-sectional bi- and multivariable analyses, the MS was strongly associated and showed monotonic dose-response relationships with TL (p-values <0.05). However, only the MS but not TL was associated with all-cause mortality during a median follow-up of 12.5 years. After controlling for potential covariates and TL, hazard ratios (95% CI) for all-cause mortality for low, moderate and high levels of the MS defined by 1, 2-5 and >5 CpG sites with aberrant methylation were 2.24 (1.13-4.41), 3.31 (1.76-6.22) and 6.33 (3.22-12.41) compared to a MS of 0, respectively. Our investigation shows that the epigenetic-based MS is strongly associated with TL, a broadly accepted aging biomarker, and at the same time shows much stronger associations with all-cause mortality than the latter.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
This article has been republished with minor changes. These changes do not impact the academic content of the article.
Current address: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA
ISSN:1559-2294
1559-2308
1559-2308
DOI:10.1080/15592294.2018.1514853