Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume.
Ageing
Alzheimer’s disease
Cognition
DNA methylation
Epigenetics
Hippocampal volume
Journal
GeroScience
ISSN: 2509-2723
Titre abrégé: Geroscience
Pays: Switzerland
ID NLM: 101686284
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
07
02
2022
accepted:
30
03
2022
pubmed:
22
4
2022
medline:
24
6
2022
entrez:
21
4
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35445885
doi: 10.1007/s11357-022-00558-8
pii: 10.1007/s11357-022-00558-8
pmc: PMC9213584
doi:
Substances chimiques
Amyloid beta-Peptides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1807-1823Subventions
Organisme : NIA NIH HHS
ID : R01 AG071514
Pays : United States
Investigateurs
Michael Weiner
(M)
Paul Aisen
(P)
Ronald Petersen
(R)
Clifford R Jack
(CR)
William Jagust
(W)
John Q Trojanowki
(JQ)
Arthur W Toga
(AW)
Laurel Beckett
(L)
Robert C Green
(RC)
Andrew J Saykin
(AJ)
John C Morris
(JC)
Leslie M Shaw
(LM)
Enchi Liu
(E)
Tom Montine
(T)
Ronald G Thomas
(RG)
Michael Donohue
(M)
Sarah Walter
(S)
Devon Gessert
(D)
Tamie Sather
(T)
Gus Jiminez
(G)
Danielle Harvey
(D)
Matthew Bernstein
(M)
Nick Fox
(N)
Paul Thompson
(P)
Norbert Schuff
(N)
Charles DeCArli
(C)
Bret Borowski
(B)
Jeff Gunter
(J)
Matt Senjem
(M)
Prashanthi Vemuri
(P)
David Jones
(D)
Kejal Kantarci
(K)
Chad Ward
(C)
Robert A Koeppe
(RA)
Norm Foster
(N)
Eric M Reiman
(EM)
Kewei Chen
(K)
Chet Mathis
(C)
Susan Landau
(S)
Nigel J Cairns
(NJ)
Erin Householder
(E)
Lisa Taylor Reinwald
(LT)
Virginia Lee
(V)
Magdalena Korecka
(M)
Michal Figurski
(M)
Karen Crawford
(K)
Scott Neu
(S)
Tatiana M Foroud
(TM)
Steven Potkin
(S)
Li Shen
(L)
Faber Kelley
(F)
Sungeun Kim
(S)
Kwangsik Nho
(K)
Zaven Kachaturian
(Z)
Richard Frank
(R)
Peter J Snyder
(PJ)
Susan Molchan
(S)
Jeffrey Kaye
(J)
Joseph Quinn
(J)
Betty Lind
(B)
Raina Carter
(R)
Sara Dolen
(S)
Lon S Schneider
(LS)
Sonia Pawluczyk
(S)
Mauricio Beccera
(M)
Liberty Teodoro
(L)
Bryan M Spann
(BM)
James Brewer
(J)
Helen Vanderswag
(H)
Adam Fleisher
(A)
Judith L Heidebrink
(JL)
Joanne L Lord
(JL)
Ronald Petersen
(R)
Sara S Mason
(SS)
Colleen S Albers
(CS)
David Knopman
(D)
Kris Johnson
(K)
Rachelle S Doody
(RS)
Javier Villanueva Meyer
(JV)
Munir Chowdhury
(M)
Susan Rountree
(S)
Mimi Dang
(M)
Yaakov Stern
(Y)
Lawrence S Honig
(LS)
Karen L Bell
(KL)
Beau Ances
(B)
Maria Carroll
(M)
Sue Leon
(S)
Erin Householder
(E)
Mark A Mintun
(MA)
Stacy Schneider
(S)
Angela OliverNG
(A)
Randall Griffith
(R)
David Clark
(D)
David Geldmacher
(D)
John Brockington
(J)
Erik Roberson
(E)
Hillel Grossman
(H)
Effie Mitsis
(E)
Leyla deToledo-Morrell
(L)
Raj C Shah
(RC)
Ranjan Duara
(R)
Daniel Varon
(D)
Maria T Greig
(MT)
Peggy Roberts
(P)
Marilyn Albert
(M)
Chiadi Onyike
(C)
Daniel D ' Agostino
(DD')
Stephanie Kielb
(S)
James E Galvin
(JE)
Dana M Pogorelec
(DM)
Brittany Cerbone
(B)
Christina A Michel
(CA)
Henry Rusinek
(H)
Mony J de Leon
(MJ)
Lidia Glodzik
(L)
Susan De Santi
(S)
P Murali Doraiswamy
(PM)
Jeffrey R Petrella
(JR)
Terence Z Wong
(TZ)
Steven E Arnold
(SE)
Jason H Karlawish
(JH)
David A Wolk
(DA)
Charles D Smith
(CD)
Greg Jicha
(G)
Peter Hardy
(P)
Partha Sinha
(P)
Elizabeth Oates
(E)
Gary Conrad
(G)
Oscar L Lopez
(OL)
Mary Ann Oakley
(MA)
Donna M Simpson
(DM)
Anton P Porsteinsson
(AP)
Bonnie S Goldstein
(BS)
Kim Martin
(K)
Kelly M Makino
(KM)
M Saleem Ismail
(MS)
Connie Brand
(C)
Ruth A Mulnard
(RA)
Gaby Thai
(G)
Catherine Mc Adams Ortiz
(C)
Kyle Womack
(K)
Dana Mathews
(D)
Mary Quiceno
(M)
Ramon Diaz Arrastia
(RD)
Richard King
(R)
Myron Weiner
(M)
Kristen Martin Cook
(KM)
Michael DeVous
(M)
Allan I Levey
(AI)
James J Lah
(JJ)
Janet S Cellar
(JS)
Jeffrey M Burns
(JM)
Heather S Anderson
(HS)
Russell H Swerdlow
(RH)
Liana Apostolova
(L)
Kathleen Tingus
(K)
Ellen Woo
(E)
Daniel H S Silverman
(DHS)
Po H Lu
(PH)
George Bartzokis
(G)
Neill R Graff Radford
(NRG)
Francine ParfittH
(F)
Tracy Kendall
(T)
Heather Johnson
(H)
Martin R Farlow
(MR)
Ann Marie Hake
(AM)
Brandy R Matthews
(BR)
Scott Herring
(S)
Cynthia Hunt
(C)
Christopher H van Dyck
(CH)
Richard E Carson
(RE)
Martha G MacAvoy
(MG)
Howard Chertkow
(H)
Howard Bergman
(H)
Chris Hosein
(C)
Sandra Black
(S)
Bojana Stefanovic
(B)
Curtis Caldwell
(C)
Ging Yuek Robin Hsiung
(GYR)
Howard Feldman
(H)
Benita Mudge
(B)
Michele Assaly Past
(MA)
Andrew Kertesz
(A)
John Rogers
(J)
Dick Trost
(D)
Charles Bernick
(C)
Donna Munic
(D)
Diana Kerwin
(D)
Marek Marsel Mesulam
(MM)
Kristine Lipowski
(K)
Chuang Kuo Wu
(CK)
Nancy Johnson
(N)
Carl Sadowsky
(C)
Walter Martinez
(W)
Teresa Villena
(T)
Raymond Scott Turner
(RS)
Kathleen Johnson
(K)
Brigid Reynolds
(B)
Reisa A Sperling
(RA)
Keith A Johnson
(KA)
Gad Marshall
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Meghan Frey
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Jerome Yesavage
(J)
Joy L Taylor
(JL)
Barton Lane
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Allyson Rosen
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Jared Tinklenberg
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Marwan N Sabbagh
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Christine M Belden
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Sandra A Jacobson
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Sherye A Sirrel
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Neil Kowall
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Ronald Killiany
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Andrew E Budson
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Alexander Norbash
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Patricia Lynn Johnson
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Thomas O Obisesan
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Saba Wolday
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Joanne Allard
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Alan Lerner
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Leon Hudson
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Evan Fletcher
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Owen Carmichael
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Charles DeCarli
(C)
Smita Kittur
(S)
Michael Borrie
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T Y Lee
(TY)
Rob Bartha
(R)
Sterling Johnson
(S)
Sanjay Asthana
(S)
Cynthia M Carlsson
(CM)
Steven G Potkin
(SG)
Adrian Preda
(A)
Dana Nguyen
(D)
Pierre Tariot
(P)
Adam Fleisher
(A)
Stephanie Reeder
(S)
Vernice Bates
(V)
Horacio Capote
(H)
Michelle Rainka
(M)
Douglas W Scharre
(DW)
Maria Kataki
(M)
Anahita Adeli
(A)
Earl A Zimmerman
(EA)
Dzintra Celmins
(D)
Alice D Brown
(AD)
Godfrey D Pearlson
(GD)
Karen Blank
(K)
Karen Anderson
(K)
Robert B Santulli
(RB)
Tamar J Kitzmiller
(TJ)
Eben S Schwartz
(ES)
Kaycee M SinkS
(KM)
Jeff D Williamson
(JD)
Pradeep Garg
(P)
Franklin Watkins
(F)
Brian R Ott
(BR)
Henry Querfurth
(H)
Geoffrey Tremont
(G)
Stephen Salloway
(S)
Paul Malloy
(P)
Stephen Correia
(S)
Howard J Rosen
(HJ)
Bruce L Miller
(BL)
Jacobo Mintzer
(J)
Kenneth Spicer
(K)
David Bachman
(D)
Elizabether Finger
(E)
Stephen Pasternak
(S)
Irina Rachinsky
(I)
John Rogers
(J)
Andrew Kertesz
(A)
Dick Drost
(D)
Nunzio Pomara
(N)
Raymundo Hernando
(R)
Antero Sarrael
(A)
Susan K Schultz
(SK)
Laura L Boles Ponto
(LL)
Hyungsub Shim
(H)
Karen Elizabeth Smith
(KE)
Norman Relkin
(N)
Gloria Chaing
(G)
Lisa Raudin
(L)
Amanda Smith
(A)
Kristin Fargher
(K)
Balebail Ashok Raj
(BA)
Christopher Fowler
(C)
Stephanie R Rainey-Smith
(SR)
Sabine Bird
(S)
Julia Bomke
(J)
Pierrick Bourgeat
(P)
Belinda M Brown
(BM)
Samantha C Burnham
(SC)
Ashley I Bush
(AI)
Carolyn Chadunow
(C)
Steven Collins
(S)
James Doecke
(J)
Vincent Dore
(V)
Kathryn A Ellis
(KA)
Lis Evered
(L)
Amir Fazlollahi
(A)
Jurgen Fripp
(J)
Samantha L Gardener
(SL)
Simon Gibson
(S)
Robert Grenfell
(R)
Elise Harrison
(E)
Richard Head
(R)
Liang Jin
(L)
Adrian Kamer
(A)
Fiona Lamb
(F)
Nicola T Lautenschlager
(NT)
Simon M Laws
(SM)
Qiao-Xin Li
(QX)
Lucy Lim
(L)
Yen Ying Lim
(YY)
Andrea Louey
(A)
S Lance Macaulay
(SL)
Lucy Mackintosh
(L)
Ralph N Martins
(RN)
Paul Maruff
(P)
Colin L Masters
(CL)
Simon McBride
(S)
Lidija Milicic
(L)
Kelly Pertile
(K)
Tenielle Porter
(T)
Morgan Radler
(M)
Joanne Robertson
(J)
Mark Rodrigues
(M)
Christopher C Rowe
(CC)
Rebecca Rumble
(R)
Olivier Salvado
(O)
Greg Savage
(G)
Rosita Shishegar
(R)
Brendan Silbert
(B)
Magdalene Soh
(M)
Hamid R Sohrabi
(HR)
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(C)
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(B)
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(R)
Michael Vacher
(M)
Shiji Varghese
(S)
Victor L Villemagne
(VL)
Michael Weinborn
(M)
Michael Woodward
(M)
Ying Xia
(Y)
David Ames
(D)
Informations de copyright
© 2022. The Author(s).
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