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

doi:10.1007/s11357-022-00558-8

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

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24 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	1807-1823
Número de páginas	17
Publicación	GeroScience
Volumen	44
N.º	3
DOI	https://doi.org/10.1007/s11357-022-00558-8
Estado	Published - jun 2022

Nota bibliográfica

Publisher Copyright:
© The Author(s) 2022.

Financiación

Open Access funding enabled and organized by CAUL and its Member Institutions Funding for the AIBL study was provided in part by the study partners (Commonwealth Scientific Industrial and research Organisation (CSIRO), Edith Cowan University (ECU), Mental Health Research Institute (MHRI), National Ageing Research Institute (NARI), Austin Health, CogState Ltd.). The AIBL study has also received support from the National Health and Medical Research Council (NHMRC) and the Dementia Collaborative Research Centres program (DCRC2), as well as funding from the Science and Industry Endowment Fund (SIEF) and the Cooperative Research Centre (CRC) for Mental Health—funded through the CRC Program, an Australian Government Initiative. Funding for this research was also supported through a NHMRC grant (GNT1161706) awarded to SML. Some of the DNAm data were generated by funding by the from the National Health and Medical Research Council (NHMRC) Boosting Dementia Research Grant (1151854) linked to the Joint Programming Neurodegenerative Disease (JPND) BRAIN-MEND grant awarded to NA, SML. These data are available from the GEO repository accession number GSE153712. We thank all the investigators within the AIBL who contributed to the design and implementation of the resource and/or provided data but did not actively participate in the development, analysis, interpretation or writing of this current study. A complete listing of AIBL investigators can be found at https://aibl.csiro.au/about/aibl-research-team/. Australian Imaging, Biomarkers and Lifestyle (AIBL) Study* *Data used in the preparation of this article was obtained from the Australian Imaging Biomarkers and Lifestyle flagship study of ageing (AIBL) funded by the Commonwealth Scientific and Industrial Research Organisation (CSIRO). The AIBL investigators, unless listed, contributed data but did not participate in analysis or writing of this report. AIBL researchers are listed at www.aibl.csiro.au. Christopher Fowler11, Stephanie R. Rainey-Smith14,15,16, Sabine Bird14, Julia Bomke7, Pierrick Bourgeat7, Belinda M. Brown15, Samantha C. Burnham1,5, Ashley I. Bush11, Carolyn Chadunow11, Steven Collins11, James Doecke1,7, Vincent Dore5,6, Kathryn A. Ellis11,17,18, Lis Evered19, Amir Fazlollahi5, Jurgen Fripp5, Samantha L. Gardener14, Simon Gibson5, Robert Grenfell5, Elise Harrison11, Richard Head5, Liang Jin11, Adrian Kamer11, Fiona Lamb6, Nicola T. Lautenschlager17, Simon M. Laws1,2,4, Qiao-Xin Li11, Lucy Lim14, Yen Ying Lim8,11, Andrea Louey11, S. Lance Macaulay5, Lucy Mackintosh11, Ralph N. Martins14,20, Paul Maruff11,12, Colin L. Masters11, Simon McBride5, Lidija Milicic1,2, Kelly Pertile11, Tenielle Porter1,2,4, Morgan Radler11, Joanne Robertson11, Mark Rodrigues14, Christopher C. Rowe6,11, Rebecca Rumble11, Olivier Salvado21, Greg Savage22, Rosita Shishegar5.

Financiadores	Número del financiador
Science and Industry Endowment Fund
Austin Health
Joint Programming Neurodegenerative Disease
Cogstate Ltd.
CAUL
Edith Cowan University
Institute for Mental Health Research
Australian National Health and Medical Research Council
Commonwealth Scientific and Industrial Research Organisation
National Ageing Research Institute
Cooperative Research Centres, Australian Government Department of Industry	1151854, GNT1161706
Cooperative Research Centres, Australian Government Department of Industry

ASJC Scopus subject areas

Aging
Veterinary (miscellaneous)
Complementary and alternative medicine
Geriatrics and Gerontology
Cardiology and Cardiovascular Medicine

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10.1007/s11357-022-00558-8

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title = "Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume",

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{\textquoteright}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{\textquoteright}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{\textquoteright}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.",

keywords = "Ageing, Alzheimer{\textquoteright}s disease, Cognition, DNA methylation, Epigenetics, Hippocampal volume",

author = "Lidija Milicic and Michael Vacher and Tenielle Porter and Vincent Dor{\'e} and Burnham, \{Samantha C.\} and Pierrick Bourgeat and Rosita Shishegar and James Doecke and Armstrong, \{Nicola J.\} and Rick Tankard and Paul Maruff and Masters, \{Colin L.\} and Rowe, \{Christopher C.\} and Villemagne, \{Victor L.\} and Laws, \{Simon M.\} and Raj, \{Balebail Ashok\} and Kristin Fargher and Amanda Smith and Lisa Raudin and Gloria Chaing and Norman Relkin and Smith, \{Karen Elizabeth\} and Hyungsub Shim and \{Boles Ponto\}, \{Laura L.\} and Schultz, \{Susan K.\} and Antero Sarrael and Raymundo Hernando and Nunzio Pomara and Dick Drost and Andrew Kertesz and John Rogers and Irina Rachinsky and Stephen Pasternak and Elizabether Finger and David Bachman and Kenneth Spicer and Jacobo Mintzer and Miller, \{Bruce L.\} and Rosen, \{Howard J.\} and Stephen Correia and Paul Malloy and Stephen Salloway and Geoffrey Tremont and Henry Querfurth and Ott, \{Brian R.\} and Franklin Watkins and Pradeep Garg and Richard King and Greg Jicha and Scott Neu",

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doi = "10.1007/s11357-022-00558-8",

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AU - Shishegar, Rosita

AU - Doecke, James

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AU - Villemagne, Victor L.

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AU - Raj, Balebail Ashok

AU - Fargher, Kristin

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AU - Chaing, Gloria

AU - Relkin, Norman

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AU - Sarrael, Antero

AU - Hernando, Raymundo

AU - Pomara, Nunzio

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AU - Kertesz, Andrew

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AU - Rosen, Howard J.

AU - Correia, Stephen

AU - Malloy, Paul

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AU - Jicha, Greg

AU - Neu, Scott

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N2 - 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.

AB - 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.

KW - Ageing

KW - Alzheimer’s disease

KW - Cognition

KW - DNA methylation

KW - Epigenetics

KW - Hippocampal volume

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VL - 44

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JO - GeroScience

JF - GeroScience

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

Resumen

Nota bibliográfica

Financiación

ASJC Scopus subject areas

Acceder al documento

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