Journal Article
Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume
Lidija Milicic; Michael Vacher; Tenielle Porter; Vincent Doré; Samantha C. Burnham; Pierrick Bourgeat; Rosita Shishegar; James Doecke; Nicola J. Armstrong; Rick Tankard; Paul Maruff; Colin L. Masters; Christopher C. Rowe; Victor L. Villemagne; Simon M. Laws; Michael Weiner; Paul Aisen; Ronald Petersen; Clifford R. Jack; William Jagust; John Q. Trojanowki; Arthur W. Toga; Laurel Beckett; Robert C. Green; Andrew J. Saykin; John C. Morris; Leslie M. Shaw; Enchi Liu; Tom Montine; Ronald G. Thomas; Michael Donohue; Sarah Walter; Devon Gessert; Tamie Sather; Gus Jiminez; Danielle Harvey; Matthew Bernstein; Nick Fox; Paul Thompson; Norbert Schuff; Charles DeCArli; Bret Borowski; Jeff Gunter; Matt Senjem; Prashanthi Vemuri; David Jones; Kejal Kantarci; Chad Ward; Robert A. Koeppe; Norm Foster; Eric M. Reiman; Kewei Chen; Chet Mathis; Susan Landau; Nigel J. Cairns; Erin Householder; Lisa Taylor Reinwald; Virginia Lee; Magdalena Korecka; Michal Figurski; Karen Crawford; Scott Neu; Tatiana M. Foroud; Steven Potkin; Li Shen; Faber Kelley; Sungeun Kim; Kwangsik Nho; Zaven Kachaturian; Richard Frank; Peter J. Snyder; Susan Molchan; Jeffrey Kaye; Joseph Quinn; Betty Lind; Raina Carter; Sara Dolen; Lon S. Schneider; Sonia Pawluczyk; Mauricio Beccera; Liberty Teodoro; Bryan M. Spann; James Brewer; Helen Vanderswag; Adam Fleisher; Judith L. Heidebrink; Joanne L. Lord; Ronald Petersen; Sara S. Mason; Colleen S. Albers; David Knopman; Kris Johnson; Rachelle S. Doody; Javier Villanueva Meyer; Munir Chowdhury; Susan Rountree; Mimi Dang; Yaakov Stern; Lawrence S. Honig; Karen L. Bell; Beau Ances; Maria Carroll; Sue Leon; Erin Householder; Mark A. Mintun; Stacy Schneider; Angela OliverNG; Randall Griffith; David Clark; David Geldmacher; John Brockington; Erik Roberson; Hillel Grossman; Effie Mitsis; Leyla deToledo-Morrell; Raj C. Shah; Ranjan Duara; Daniel Varon; Maria T. Greig; Peggy Roberts; Marilyn Albert; Chiadi Onyike; Daniel D.’ Agostino; Stephanie Kielb; James E. Galvin; Dana M. Pogorelec; Brittany Cerbone; Christina A. Michel; Henry Rusinek; Mony J. de Leon; Lidia Glodzik; Susan De Santi; P. Murali Doraiswamy; Jeffrey R. Petrella; Terence Z. Wong; Steven E. Arnold; Jason H. Karlawish; David A. Wolk; Charles D. Smith; Greg Jicha; Peter Hardy; Partha Sinha; Elizabeth Oates; Gary Conrad; Oscar L. Lopez; Mary Ann Oakley; Donna M. Simpson; Anton P. Porsteinsson; Bonnie S. Goldstein; Kim Martin; Kelly M. Makino; M. Saleem Ismail; Connie Brand; Ruth A. Mulnard; Gaby Thai; Catherine Mc Adams Ortiz; Kyle Womack; Dana Mathews; Mary Quiceno; Ramon Diaz Arrastia; Richard King; Myron Weiner; Kristen Martin Cook; Michael DeVous; Allan I. Levey; James J. Lah; Janet S. Cellar; Jeffrey M. Burns; Heather S. Anderson; Russell H. Swerdlow; Liana Apostolova; Kathleen Tingus; Ellen Woo; Daniel H. S. Silverman; Po H. Lu; George Bartzokis; Neill R. Graff Radford; Francine ParfittH; Tracy Kendall; Heather Johnson; Martin R. Farlow; Ann Marie Hake; Brandy R. Matthews; Scott Herring; Cynthia Hunt; Christopher H. van Dyck; Richard E. Carson; Martha G. MacAvoy; Howard Chertkow; Howard Bergman; Chris Hosein; Sandra Black; Bojana Stefanovic; Curtis Caldwell; Ging Yuek Robin Hsiung; Howard Feldman; Benita Mudge; Michele Assaly Past; Andrew Kertesz; John Rogers; Dick Trost; Charles Bernick; Donna Munic; Diana Kerwin; Marek Marsel Mesulam; Kristine Lipowski; Chuang Kuo Wu; Nancy Johnson; Carl Sadowsky; Walter Martinez; Teresa Villena; Raymond Scott Turner; Kathleen Johnson; Brigid Reynolds; Reisa A. Sperling; Keith A. Johnson; Gad Marshall; Meghan Frey; Jerome Yesavage; Joy L. Taylor; Barton Lane; Allyson Rosen; Jared Tinklenberg; Marwan N. Sabbagh; Christine M. Belden; Sandra A. Jacobson; Sherye A. Sirrel; Neil Kowall; Ronald Killiany; Andrew E. Budson; Alexander Norbash; Patricia Lynn Johnson; Thomas O. Obisesan; Saba Wolday; Joanne Allard; Alan Lerner; Paula Ogrocki; Leon Hudson; Evan Fletcher; Owen Carmichael; John Olichney; Charles DeCarli; Smita Kittur; Michael Borrie; T. Y. Lee; Rob Bartha; Sterling Johnson; Sanjay Asthana; Cynthia M. Carlsson; Steven G. Potkin; Adrian Preda; Dana Nguyen; Pierre Tariot; Adam Fleisher; Stephanie Reeder; Vernice Bates; Horacio Capote; Michelle Rainka; Douglas W. Scharre; Maria Kataki; Anahita Adeli; Earl A. Zimmerman; Dzintra Celmins; Alice D. Brown; Godfrey D. Pearlson; Karen Blank; Karen Anderson; Robert B. Santulli; Tamar J. Kitzmiller; Eben S. Schwartz; Kaycee M. SinkS; Jeff D. Williamson; Pradeep Garg; Franklin Watkins; Brian R. Ott; Henry Querfurth; Geoffrey Tremont; Stephen Salloway; Paul Malloy; Stephen Correia; Howard J. Rosen; Bruce L. Miller; Jacobo Mintzer; Kenneth Spicer; David Bachman; Elizabether Finger; Stephen Pasternak; Irina Rachinsky; John Rogers; Andrew Kertesz; Dick Drost; Nunzio Pomara; Raymundo Hernando; Antero Sarrael; Susan K. Schultz; Laura L. Boles Ponto; Hyungsub Shim; Karen Elizabeth Smith; Norman Relkin; Gloria Chaing; Lisa Raudin; Amanda Smith; Kristin Fargher; Balebail Ashok Raj; Christopher Fowler; Stephanie R. Rainey-Smith; Sabine Bird; Julia Bomke; Pierrick Bourgeat; Belinda M. Brown; Samantha C. Burnham; Ashley I. Bush; Carolyn Chadunow; Steven Collins; James Doecke; Vincent Dore; Kathryn A. Ellis; Lis Evered; Amir Fazlollahi; Jurgen Fripp; Samantha L. Gardener; Simon Gibson; Robert Grenfell; Elise Harrison; Richard Head; Liang Jin; Adrian Kamer; Fiona Lamb; Nicola T. Lautenschlager; Simon M. Laws; Qiao-Xin Li; Lucy Lim; Yen Ying Lim; Andrea Louey; S. Lance Macaulay; Lucy Mackintosh; Ralph N. Martins; Paul Maruff; Colin L. Masters; Simon McBride; Lidija Milicic; Kelly Pertile; Tenielle Porter; Morgan Radler; Joanne Robertson; Mark Rodrigues; Christopher C. Rowe; Rebecca Rumble; Olivier Salvado; Greg Savage; Rosita Shishegar; Brendan Silbert; Magdalene Soh; Hamid R. Sohrabi; Kevin Taddei; Tania Taddei; Christine Thai; Brett Trounson; Regan Tyrrel; Michael Vacher; Shiji Varghese; Victor L. Villemagne; Michael Weinborn; Michael Woodward; Ying Xia; David Ames
GeroScience · Vol. 44, Issue 3 · pp. 1807-1823 · 2022
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.