Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume.

Autor: Milicic L; Centre for Precision Health, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia, 6027, Australia.; Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, 6027, Australia., Vacher M; Centre for Precision Health, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia, 6027, Australia.; Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, 6027, Australia.; CSIRO Health and Biosecurity, Australian E-Health Research Centre, Floreat, Western Australia, 6014, Australia., Porter T; Centre for Precision Health, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia, 6027, Australia.; Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, 6027, Australia.; School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, Western Australia, 6102, Australia., Doré V; Australian E-Health Research Centre, CSIRO, Parkville, Victoria, 3052, Australia.; Department of Molecular Imaging and Therapy and Centre for PET, Austin Health, Heidelberg, Victoria, Australia., Burnham SC; Centre for Precision Health, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia, 6027, Australia.; Australian E-Health Research Centre, CSIRO, Parkville, Victoria, 3052, Australia., Bourgeat P; Australian E-Health Research Centre, CSIRO, Herston, Queensland, 4029, Australia., Shishegar R; Australian E-Health Research Centre, CSIRO, Parkville, Victoria, 3052, Australia.; School of Psychological Sciences and Turner Institute for Brain and Mental Health, Monash University, Melbourne, VIC, Australia., Doecke J; Centre for Precision Health, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia, 6027, Australia.; Australian E-Health Research Centre, CSIRO, Herston, Queensland, 4029, Australia., Armstrong NJ; Department of Mathematics and Statistics, Curtin University, Bentley, Western Australia, Australia., Tankard R; School of Mathematics and Statistics, Murdoch University, Perth, Western Australia, Australia., Maruff P; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, 3052, Australia.; Cogstate Ltd, Melbourne, VIC, Australia., Masters CL; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, 3052, Australia., Rowe CC; Department of Molecular Imaging and Therapy and Centre for PET, Austin Health, Heidelberg, Victoria, Australia.; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, 3052, Australia., Villemagne VL; Centre for Precision Health, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia, 6027, Australia.; Department of Molecular Imaging and Therapy and Centre for PET, Austin Health, Heidelberg, Victoria, Australia.; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA., Laws SM; Centre for Precision Health, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia, 6027, Australia. s.laws@ecu.edu.au.; Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, 6027, Australia. s.laws@ecu.edu.au.; School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, Western Australia, 6102, Australia. s.laws@ecu.edu.au.
Jazyk: angličtina
Zdroj: GeroScience [Geroscience] 2022 Jun; Vol. 44 (3), pp. 1807-1823. Date of Electronic Publication: 2022 Apr 21.
DOI: 10.1007/s11357-022-00558-8
Abstrakt: The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer's Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer's disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes.
(© 2022. The Author(s).)
Databáze: MEDLINE
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