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Ageing affects subtelomeric DNA methylation in blood cells from a large European population enrolled in the MARK-AGE study

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2021

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Bacalini, Maria Giulia
Reale, Anna
Malavolta, Marco
Ciccarone, Fabio
Dollé, Martijn E T
Jansen, Eugène
Caiafa, Paola
Zampieri, Michele
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GeroScience. Springer. 2021, 43(3), pp. 1283-1302. ISSN 2509-2715. eISSN 2509-2723. Available under: doi: 10.1007/s11357-021-00347-9

Zusammenfassung

Ageing leaves characteristic traces in the DNA methylation make-up of the genome. However, the importance of DNA methylation in ageing remains unclear. The study of subtelomeric regions could give promising insights into this issue. Previously reported associations between susceptibility to age-related diseases and epigenetic instability at subtelomeres suggest that the DNA methylation profile of subtelomeres undergoes remodelling during ageing. In the present work, this hypothesis has been tested in the context of the European large-scale project MARK-AGE. In this cross-sectional study, we profiled the DNA methylation of chromosomes 5 and 21 subtelomeres, in more than 2000 age-stratified women and men recruited in eight European countries. The study included individuals from the general population as well as the offspring of nonagenarians and Down syndrome subjects, who served as putative models of delayed and accelerated ageing, respectively. Significant linear changes of subtelomeric DNA methylation with increasing age were detected in the general population, indicating that subtelomeric DNA methylation changes are typical signs of ageing. Data also show that, compared to the general population, the dynamics of age-related DNA methylation changes are attenuated in the offspring of centenarian, while they accelerate in Down syndrome individuals. This result suggests that subtelomeric DNA methylation changes reflect the rate of ageing progression. We next attempted to trace the age-related changes of subtelomeric methylation back to the influence of diverse variables associated with methylation variations in the population, including demographics, dietary/health habits and clinical parameters. Results indicate that the effects of age on subtelomeric DNA methylation are mostly independent of all other variables evaluated.

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570 Biowissenschaften, Biologie

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ISO 690BACALINI, Maria Giulia, Anna REALE, Marco MALAVOLTA, Fabio CICCARONE, Maria MORENO-VILLANUEVA, Martijn E T DOLLÉ, Eugène JANSEN, Alexander BÜRKLE, Paola CAIAFA, Michele ZAMPIERI, 2021. Ageing affects subtelomeric DNA methylation in blood cells from a large European population enrolled in the MARK-AGE study. In: GeroScience. Springer. 2021, 43(3), pp. 1283-1302. ISSN 2509-2715. eISSN 2509-2723. Available under: doi: 10.1007/s11357-021-00347-9
BibTex
@article{Bacalini2021-06Agein-53723,
  year={2021},
  doi={10.1007/s11357-021-00347-9},
  title={Ageing affects subtelomeric DNA methylation in blood cells from a large European population enrolled in the MARK-AGE study},
  number={3},
  volume={43},
  issn={2509-2715},
  journal={GeroScience},
  pages={1283--1302},
  author={Bacalini, Maria Giulia and Reale, Anna and Malavolta, Marco and Ciccarone, Fabio and Moreno-Villanueva, Maria and Dollé, Martijn E T and Jansen, Eugène and Bürkle, Alexander and Caiafa, Paola and Zampieri, Michele}
}
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    <dcterms:abstract xml:lang="eng">Ageing leaves characteristic traces in the DNA methylation make-up of the genome. However, the importance of DNA methylation in ageing remains unclear. The study of subtelomeric regions could give promising insights into this issue. Previously reported associations between susceptibility to age-related diseases and epigenetic instability at subtelomeres suggest that the DNA methylation profile of subtelomeres undergoes remodelling during ageing. In the present work, this hypothesis has been tested in the context of the European large-scale project MARK-AGE. In this cross-sectional study, we profiled the DNA methylation of chromosomes 5 and 21 subtelomeres, in more than 2000 age-stratified women and men recruited in eight European countries. The study included individuals from the general population as well as the offspring of nonagenarians and Down syndrome subjects, who served as putative models of delayed and accelerated ageing, respectively. Significant linear changes of subtelomeric DNA methylation with increasing age were detected in the general population, indicating that subtelomeric DNA methylation changes are typical signs of ageing. Data also show that, compared to the general population, the dynamics of age-related DNA methylation changes are attenuated in the offspring of centenarian, while they accelerate in Down syndrome individuals. This result suggests that subtelomeric DNA methylation changes reflect the rate of ageing progression. We next attempted to trace the age-related changes of subtelomeric methylation back to the influence of diverse variables associated with methylation variations in the population, including demographics, dietary/health habits and clinical parameters. Results indicate that the effects of age on subtelomeric DNA methylation are mostly independent of all other variables evaluated.</dcterms:abstract>
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