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Title: Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume.
Austin Authors: Milicic, Lidija;Vacher, Michael;Porter, Tenielle;Doré, Vincent ;Burnham, Samantha C;Bourgeat, Pierrick;Shishegar, Rosita;Doecke, James;Armstrong, Nicola J;Tankard, Rick;Maruff, Paul;Masters, Colin L ;Rowe, Christopher C ;Villemagne, Victor L ;Laws, Simon M
Affiliation: Molecular Imaging and Therapy
The Florey Institute of Neuroscience and Mental Health
School of Psychological Sciences and Turner Institute for Brain and Mental Health, Monash University, Melbourne, VIC, Australia
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
Australian E-Health Research Centre, CSIRO, Herston, Queensland, 4029, Australia
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
Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia
School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, Western Australia, 6102, Australia
The University of Melbourne, Parkville, VIC, Australia
Cogstate Ltd, Melbourne, VIC, Australia
Department of Mathematics and Statistics, Curtin University, Bentley, Western Australia, Australia
School of Mathematics and Statistics, Murdoch University, Perth, Western Australia
CSIRO Health and Biosecurity, Australian E-Health Research Centre, Floreat, Western Australia, 6014, Australia
Issue Date: Jun-2022
Date: 2022-04-21
Publication information: GeroScience 2022; 44(3): 1807-1823
Abstract: 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.
DOI: 10.1007/s11357-022-00558-8
ORCID: 0000-0002-8051-0558
Journal: GeroScience
PubMed URL: 35445885
PubMed URL:
Type: Journal Article
Subjects: Ageing
Alzheimer’s disease
DNA methylation
Hippocampal volume
Appears in Collections:Journal articles

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