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

L. Milicic; M. Vacher; T. Porter; V. Doré; S.C. Burnham; P. Bourgeat; R. Shishegar; J. Doecke; N.J. Armstrong; R. Tankard; P. Maruff; C.L. Masters; C.C. Rowe; V.L. Villemagne; S.M. Laws; M. Weiner; P. Aisen; R. Petersen; C.R. Jack; W. Jagust; J.Q. Trojanowki; A.W. Toga; L. Beckett; R.C. Green; A.J. Saykin; J.C. Morris; L.M. Shaw; E. Liu; T. Montine; R.G. Thomas; M. Donohue; S. Walter; D. Gessert; T. Sather; G. Jiminez; D. Harvey; M. Bernstein; N. Fox; P. Thompson; N. Schuff; C. DeCArli; B. Borowski; J. Gunter; M. Senjem; P. Vemuri; D. Jones; K. Kantarci; C. Ward; R.A. Koeppe; N. Foster; E.M. Reiman; K. Chen; C. Mathis; S. Landau; N.J. Cairns; E. Householder; L.T. Reinwald; V. Lee; M. Korecka; M. Figurski; K. Crawford; S. Neumann; T. M. Foroud; S. Potkin; L. Shen; F. Kelley; S. Kim; K. Nho; Z. Kachaturian; R. Frank; P.J. Snyder; S. Molchan; J. Kaye; J. Quinn; B. Lind; R. Carter; S. Dolen; L.S. Schneider; S. Pawluczyk; M. Beccera; L. Teodoro; B.M. Spann; J. Brewer; H. Vanderswag; A. Fleisher; J.L. Heidebrink; J.L. Lord; S.S. Mason; C.S. Albers; D. Knopman; K. Johnson; R.S. Doody; J.V. Meyer; M. Chowdhury; S. Rountree; M. Dang; Y. Stern; L.S. Honig; K.L. Bell; B. Ances; M. Carroll; S. Leon; M.A. Mintun; S. Schneider; A. OliverNG; R. Griffith; D. Clark; D. Geldmacher; J. Brockington; E. Roberson; H. Grossman; E. Mitsis; L. deToledo-Morrell; R.C. Shah; R. Duara; D. Varon; M.T. Greig; P. Roberts; M. Albert; C. Onyike; D.D. Agostino; S. Kielb; J.E. Galvin; D.M. Pogorelec; B. Cerbone; C.A. Michel; H. Rusinek; M.J. de Leon; L. Glodzik; S. De Santi; P.M. Doraiswamy; J.R. Petrella; T.Z. Wong; S.E. Arnold; J.H. Karlawish; D.A. Wolk; C.D. Smith; G. Jicha; P. Hardy; P. Sinha; E. Oates; G. Conrad; O.L. Lopez; M.A. Oakley; D.M. Simpson; A.P. Porsteinsson; B.S. Goldstein; K. Martin; K.M. Makino; M.S. Ismail; C. Brand; R.A. Mulnard; G. Thai; C. Mc Adams Ortiz; K. Womack; D. Mathews; M. Quiceno; R.D. Arrastia; R. King; K.M. Cook; M. DeVous; A.I. Levey; J.J. Lah; J.S. Cellar; J.M. Burns; H.S. Anderson; R.H. Swerdlow; L. Apostolova; K. Tingus; E. Woo; D.H.S. Silverman; P.H. Lu; G. Bartzokis; N.R.G. Radford; F. ParfittH; T. Kendall; H. Johnson; M.R. Farlow; A.M. Hake; B.R. Matthews; S. Herring; C. Hunt; C.H. van Dyck; R.E. Carson; M.G. MacAvoy; H. Chertkow; H. Bergman; C. Hosein; S. Black; B. Stefanovic; C. Caldwell; G.Y.R. Hsiung; H. Feldman; B. Mudge; M.A. Past; A. Kertesz; J. Rogers; D. Trost; C. Bernick; D. Munic; D. Kerwin; M.M. Mesulam; K. Lipowski; C.K. Wu; N. Johnson; C. Sadowsky; W. Martinez; T. Villena; R.S. Turner; B. Reynolds; R.A. Sperling; K.A. Johnson; G. Marshall; M. Frey; J. Yesavage; J.L. Taylor; B. Lane; A. Rosen; J. Tinklenberg; M.N. Sabbagh; C.M. Belden; S.A. Jacobson; S.A. Sirrel; N. Kowall; R. Killiany; A.E. Budson; A. Norbash; P.L. Johnson; T.O. Obisesan; S. Wolday; J. Allard; A. Lerner; P. Ogrocki; L. Hudson; E. Fletcher; O. Carmichael; J. Olichney; C. DeCarli; S. Kittur; M. Borrie; T.Y. Lee; R. Bartha; S. Johnson; S. Asthana; C.M. Carlsson; S.G. Potkin; A. Preda; D. Nguyen; P. Tariot; S. Reeder; V. Bates; H. Capote; M. Rainka; D.W. Scharre; M. Kataki; A. Adeli; E.A. Zimmerman; D. Celmins; A.D. Brown; G.D. Pearlson; K. Blank; K. Anderson; R.B. Santulli; T.J. Kitzmiller; E.S. Schwartz; K.M. SinkS; J.D. Williamson; P. Garg; F. Watkins; B.R. Ott; H. Querfurth; G. Tremont; S. Salloway; P. Malloy; S. Correia; H. J. Rosen; B.L. Miller; J. Mintzer; K. Spicer; D. Bachman; E. Finger; S. Pasternak; I. Rachinsky; D. Drost; N. Pomara; R. Hernando; A. Sarrael; S.K. Schultz; L.L. Boles Ponto; H. Shim; K.E. Smith; N. Relkin; G. Chaing; L. Raudin; A. Smith; K. Fargher; B.A. Raj; C. Fowler; S.R. Rainey-Smith; P. Bird; J. Bomke; B.M. Brown; A.I. Bush; C. Chadunow; S. Collins; V. Dore; K.A. Ellis; L. Evered; A. Fazlollahi; J. Fripp; S.L. Gardener; S. Gibson; R. Grenfell; E. Harrison; R. Head; L. Jin; A. Kamer; F. Lamb; N.T. Lautenschlager; Q-X Li; L. Lim; Y.Y. Lim; A. Louey; S.L. Macaulay; L. Mackintosh; R.N. Martins; S. McBride; K. Pertile; M. Radler; J. Robertson; M. Rodrigues; R. Rumble; O. Salvado; G. Savage; B. Silbert; M. Soh; H.R. Sohrabi; K. Taddei; T. Taddei; C. Thai; B. Trounson; R. Tyrrell; S. Varghese; M. Weinborn; M. Woodward; Y. Xia; D. Ames

doi:10.1007/s11357-022-00558-8

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

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

L. Milicic, M. Vacher, T. Porter, V. Doré, S.C. Burnham, P. Bourgeat, R. Shishegar, J. Doecke, N.J. Armstrong, R. Tankard, …

GeroScience, Vol.44, pp.1807-1823

2022

DOI: https://doi.org/10.1007/s11357-022-00558-8

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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.

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Title: Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume
Authors/Creators: L. Milicic (Author/Creator)
M. Vacher (Author/Creator)
T. Porter (Author/Creator)
V. Doré (Author/Creator)
S.C. Burnham (Author/Creator)
P. Bourgeat (Author/Creator)
R. Shishegar (Author/Creator)
J. Doecke (Author/Creator)
N.J. Armstrong (Author/Creator)
R. Tankard (Author/Creator)
P. Maruff (Author/Creator)
C.L. Masters (Author/Creator)
C.C. Rowe (Author/Creator)
V.L. Villemagne (Author/Creator)
S.M. Laws (Author/Creator)
M. Weiner (Author/Creator)
P. Aisen (Author/Creator)
R. Petersen (Author/Creator)
C.R. Jack (Author/Creator)
W. Jagust (Author/Creator)
J.Q. Trojanowki (Author/Creator)
A.W. Toga (Author/Creator)
L. Beckett (Author/Creator)
R.C. Green (Author/Creator)
A.J. Saykin (Author/Creator)
J.C. Morris (Author/Creator)
L.M. Shaw (Author/Creator)
E. Liu (Author/Creator)
T. Montine (Author/Creator)
R.G. Thomas (Author/Creator)
M. Donohue (Author/Creator)
S. Walter (Author/Creator)
D. Gessert (Author/Creator)
T. Sather (Author/Creator)
G. Jiminez (Author/Creator)
D. Harvey (Author/Creator)
M. Bernstein (Author/Creator)
N. Fox (Author/Creator)
P. Thompson (Author/Creator)
N. Schuff (Author/Creator)
C. DeCArli (Author/Creator)
B. Borowski (Author/Creator)
J. Gunter (Author/Creator)
M. Senjem (Author/Creator)
P. Vemuri (Author/Creator)
D. Jones (Author/Creator)
K. Kantarci (Author/Creator)
C. Ward (Author/Creator)
R.A. Koeppe (Author/Creator)
N. Foster (Author/Creator)
E.M. Reiman (Author/Creator)
K. Chen (Author/Creator)
C. Mathis (Author/Creator)
S. Landau (Author/Creator)
N.J. Cairns (Author/Creator)
E. Householder (Author/Creator)
L.T. Reinwald (Author/Creator)
V. Lee (Author/Creator)
M. Korecka (Author/Creator)
M. Figurski (Author/Creator)
K. Crawford (Author/Creator)
S. Neumann (Author/Creator)
T. M. Foroud (Author/Creator)
S. Potkin (Author/Creator)
L. Shen (Author/Creator)
F. Kelley (Author/Creator)
S. Kim (Author/Creator)
K. Nho (Author/Creator)
Z. Kachaturian (Author/Creator)
R. Frank (Author/Creator)
P.J. Snyder (Author/Creator)
S. Molchan (Author/Creator)
J. Kaye (Author/Creator)
J. Quinn (Author/Creator)
B. Lind (Author/Creator)
R. Carter (Author/Creator)
S. Dolen (Author/Creator)
L.S. Schneider (Author/Creator)
S. Pawluczyk (Author/Creator)
M. Beccera (Author/Creator)
L. Teodoro (Author/Creator)
B.M. Spann (Author/Creator)
J. Brewer (Author/Creator)
H. Vanderswag (Author/Creator)
A. Fleisher (Author/Creator)
J.L. Heidebrink (Author/Creator)
J.L. Lord (Author/Creator)
R. Petersen (Author/Creator)
S.S. Mason (Author/Creator)
C.S. Albers (Author/Creator)
D. Knopman (Author/Creator)
K. Johnson (Author/Creator)
R.S. Doody (Author/Creator)
J.V. Meyer (Author/Creator)
M. Chowdhury (Author/Creator)
S. Rountree (Author/Creator)
M. Dang (Author/Creator)
Y. Stern (Author/Creator)
L.S. Honig (Author/Creator)
K.L. Bell (Author/Creator)
B. Ances (Author/Creator)
M. Carroll (Author/Creator)
S. Leon (Author/Creator)
E. Householder (Author/Creator)
M.A. Mintun (Author/Creator)
S. Schneider (Author/Creator)
A. OliverNG (Author/Creator)
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D. Clark (Author/Creator)
D. Geldmacher (Author/Creator)
J. Brockington (Author/Creator)
E. Roberson (Author/Creator)
H. Grossman (Author/Creator)
E. Mitsis (Author/Creator)
L. deToledo-Morrell (Author/Creator)
R.C. Shah (Author/Creator)
R. Duara (Author/Creator)
D. Varon (Author/Creator)
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H. Rusinek (Author/Creator)
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L. Glodzik (Author/Creator)
S. De Santi (Author/Creator)
P.M. Doraiswamy (Author/Creator)
J.R. Petrella (Author/Creator)
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S.E. Arnold (Author/Creator)
J.H. Karlawish (Author/Creator)
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P. Hardy (Author/Creator)
P. Sinha (Author/Creator)
E. Oates (Author/Creator)
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O.L. Lopez (Author/Creator)
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K.M. Makino (Author/Creator)
M.S. Ismail (Author/Creator)
C. Brand (Author/Creator)
R.A. Mulnard (Author/Creator)
G. Thai (Author/Creator)
C. Mc Adams Ortiz (Author/Creator)
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D. Mathews (Author/Creator)
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R.D. Arrastia (Author/Creator)
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N. Pomara (Author/Creator)
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H. Shim (Author/Creator)
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G. Chaing (Author/Creator)
L. Raudin (Author/Creator)
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R. Grenfell (Author/Creator)
E. Harrison (Author/Creator)
R. Head (Author/Creator)
L. Jin (Author/Creator)
A. Kamer (Author/Creator)
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N.T. Lautenschlager (Author/Creator)
S.M. Laws (Author/Creator)
Q-X Li (Author/Creator)
L. Lim (Author/Creator)
Y.Y. Lim (Author/Creator)
A. Louey (Author/Creator)
S.L. Macaulay (Author/Creator)
L. Mackintosh (Author/Creator)
R.N. Martins (Author/Creator)
P. Maruff (Author/Creator)
C.L. Masters (Author/Creator)
S. McBride (Author/Creator)
L. Milicic (Author/Creator)
K. Pertile (Author/Creator)
T. Porter (Author/Creator)
M. Radler (Author/Creator)
J. Robertson (Author/Creator)
M. Rodrigues (Author/Creator)
C.C. Rowe (Author/Creator)
R. Rumble (Author/Creator)
O. Salvado (Author/Creator)
G. Savage (Author/Creator)
R. Shishegar (Author/Creator)
B. Silbert (Author/Creator)
M. Soh (Author/Creator)
H.R. Sohrabi (Author/Creator)
K. Taddei (Author/Creator)
T. Taddei (Author/Creator)
C. Thai (Author/Creator)
B. Trounson (Author/Creator)
R. Tyrrell (Author/Creator)
M. Vacher (Author/Creator)
S. Varghese (Author/Creator)
V.L. Villemagne (Author/Creator)
M. Weinborn (Author/Creator)
M. Woodward (Author/Creator)
Y. Xia (Author/Creator)
D. Ames (Author/Creator)
Publication Details: GeroScience, Vol.44, pp.1807-1823
Publisher: Springer Nature
Identifiers: 991005542328807891
Copyright: © 2022 The Authors.
Murdoch Affiliation: College of Science, Health, Engineering and Education
Language: English
Resource Type: Journal article

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Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.54 Molecular & Cell Biology - Genetics; 1.54.100 Epigenetic Regulation
Web Of Science research areas: Geriatrics & Gerontology
ESI research areas: Clinical Medicine