| Title: |
Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume |
| Authors: |
Milicic, L.; Vacher, M.; Porter, T.; Doré, V.; Burnham, S.C.; Bourgeat, P.; Shishegar, R.; Doecke, J.; Armstrong, N.J.; Tankard, R.; Maruff, P.; Masters, C.L.; Rowe, C.C.; Villemagne, V.L.; Laws, S.M.; Weiner, M.; Aisen, P.; Petersen, R.; Jack, C.R.; Jagust, W.; Trojanowki, J.Q.; Toga, A.W.; Beckett, L.; Green, R.C.; Saykin, A.J.; Morris, J.C.; Shaw, L.M.; Liu, E.; Montine, T.; Thomas, R.G.; Donohue, M.; Walter, S.; Gessert, D.; Sather, T.; Jiminez, G.; Harvey, D.; Bernstein, M.; Fox, N.; Thompson, P.; Schuff, N.; DeCArli, C.; Borowski, B.; Gunter, J.; Senjem, M.; Vemuri, P.; Jones, D.; Kantarci, K.; Ward, C.; Koeppe, R.A.; Foster, N.; Reiman, E.M.; Chen, K.; Mathis, C.; Landau, S.; Cairns, N.J.; Householder, E.; Reinwald, L.T.; Lee, V.; Korecka, M.; Figurski, M.; Crawford, K.; Neumann, S.; Foroud, T. M.; Potkin, S.; Shen, L.; Kelley, F.; Kim, S.; Nho, K.; Kachaturian, Z.; Frank, R.; Snyder, P.J.; Molchan, S.; Kaye, J.; Quinn, J.; Lind, B.; Carter, R.; Dolen, S.; Schneider, L.S.; Pawluczyk, S.; Beccera, M.; Teodoro, L.; Spann, B.M.; Brewer, J.; Vanderswag, H.; Fleisher, A.; Heidebrink, J.L.; Lord, J.L.; Mason, S.S.; Albers, C.S.; Knopman, D.; Johnson, K.; Doody, R.S.; Meyer, J.V.; Chowdhury, M.; Rountree, S.; Dang, M.; Stern, Y.; Honig, L.S.; Bell, K.L.; Ances, B.; Carroll, M.; Leon, S.; Mintun, M.A.; Schneider, S.; OliverNG, A.; Griffith, R.; Clark, D.; Geldmacher, D.; Brockington, J.; Roberson, E.; Grossman, H.; Mitsis, E.; deToledo-Morrell, L.; Shah, R.C.; Duara, R.; Varon, D.; Greig, M.T.; Roberts, P.; Albert, M.; Onyike, C.; Agostino, D.D.; Kielb, S.; Galvin, J.E.; Pogorelec, D.M.; Cerbone, B.; Michel, C.A.; Rusinek, H.; de Leon, M.J.; Glodzik, L.; De Santi, S.; Doraiswamy, P.M.; Petrella, J.R.; Wong, T.Z.; Arnold, S.E.; Karlawish, J.H.; Wolk, D.A.; Smith, C.D.; Jicha, G.; Hardy, P.; Sinha, P.; Oates, E.; Conrad, G.; Lopez, O.L.; Oakley, M.A.; Simpson, D.M.; Porsteinsson, A.P.; Goldstein, B.S.; Martin, K.; Makino, K.M.; Ismail, M.S.; Brand, C.; Mulnard, R.A.; Thai, G.; Mc Adams Ortiz, C.; Womack, K.; Mathews, D.; Quiceno, M.; Arrastia, R.D.; King, R.; Cook, K.M.; DeVous, M.; Levey, A.I.; Lah, J.J.; Cellar, J.S.; Burns, J.M.; Anderson, H.S.; Swerdlow, R.H.; Apostolova, L.; Tingus, K.; Woo, E.; Silverman, D.H.S.; Lu, P.H.; Bartzokis, G.; Radford, N.R.G.; ParfittH, F.; Kendall, T.; Johnson, H.; Farlow, M.R.; Hake, A.M.; Matthews, B.R.; Herring, S.; Hunt, C.; van Dyck, C.H.; Carson, R.E.; MacAvoy, M.G.; Chertkow, H.; Bergman, H.; Hosein, C.; Black, S.; Stefanovic, B.; Caldwell, C.; Hsiung, G.Y.R.; Feldman, H.; Mudge, B.; Past, M.A.; Kertesz, A.; Rogers, J.; Trost, D.; Bernick, C.; Munic, D.; Kerwin, D.; Mesulam, M.M.; Lipowski, K.; Wu, C.K.; Johnson, N.; Sadowsky, C.; Martinez, W.; Villena, T.; Turner, R.S.; Reynolds, B.; Sperling, R.A.; Johnson, K.A.; Marshall, G.; Frey, M.; Yesavage, J.; Taylor, J.L.; Lane, B.; Rosen, A.; Tinklenberg, J.; Sabbagh, M.N.; Belden, C.M.; Jacobson, S.A.; Sirrel, S.A.; Kowall, N.; Killiany, R.; Budson, A.E.; Norbash, A.; Johnson, P.L.; Obisesan, T.O.; Wolday, S.; Allard, J.; Lerner, A.; Ogrocki, P.; Hudson, L.; Fletcher, E.; Carmichael, O.; Olichney, J.; DeCarli, C.; Kittur, S.; Borrie, M.; Lee, T.Y.; Bartha, R.; Johnson, S.; Asthana, S.; Carlsson, C.M.; Potkin, S.G.; Preda, A.; Nguyen, D.; Tariot, P.; Reeder, S.; Bates, V.; Capote, H.; Rainka, M.; Scharre, D.W.; Kataki, M.; Adeli, A.; Zimmerman, E.A.; Celmins, D.; Brown, A.D.; Pearlson, G.D.; Blank, K.; Anderson, K.; Santulli, R.B.; Kitzmiller, T.J.; Schwartz, E.S.; SinkS, K.M.; Williamson, J.D.; Garg, P.; Watkins, F.; Ott, B.R.; Querfurth, H.; Tremont, G.; Salloway, S.; Malloy, P.; Correia, S.; Rosen, H. J.; Miller, B.L.; Mintzer, J.; Spicer, K.; Bachman, D.; Finger, E.; Pasternak, S.; Rachinsky, I.; Drost, D.; Pomara, N.; Hernando, R.; Sarrael, A.; Schultz, S.K.; Boles Ponto, L.L.; Shim, H.; Smith, K.E.; Relkin, N.; Chaing, G.; Raudin, L.; Smith, A.; Fargher, K.; Raj, B.A.; Fowler, C.; Rainey-Smith, S.R.; Bird, P.; Bomke, J.; Brown, B.M.; Bush, A.I.; Chadunow, C.; Collins, S.; Dore, V.; Ellis, K.A.; Evered, L.; Fazlollahi, A.; Fripp, J.; Gardener, S.L.; Gibson, S.; Grenfell, R.; Harrison, E.; Head, R.; Jin, L.; Kamer, A.; Lamb, F.; Lautenschlager, N.T.; Li, Q-X; Lim, L.; Lim, Y.Y.; Louey, A.; Macaulay, S.L.; Mackintosh, L.; Martins, R.N.; McBride, S.; Pertile, K.; Radler, M.; Robertson, J.; Rodrigues, M.; Rumble, R.; Salvado, O.; Savage, G.; Silbert, B.; Soh, M.; Sohrabi, H.R.; Taddei, K.; Taddei, T.; Thai, C.; Trounson, B.; Tyrrell, R.; Varghese, S.; Weinborn, M.; Woodward, M.; Xia, Y.; Ames, D. |
| Source: |
Milicic, L., Vacher, M., Porter, T., Doré, V., Burnham, S.C., Bourgeat, P., Shishegar, R., Doecke, J., Armstrong, N.J. orcid:0000-0002-4477-293X , Tankard, R. orcid:0000-0002-8847-9401 , Maruff, P., Masters, C.L., Rowe, C.C., Villemagne, V.L., Laws, S.M., Weiner, M., Aisen, P., Petersen, R., Jack, C.R., Jagust, W., Trojanowki, J.Q., Toga, A.W., Beckett, L., Green, R.C., Saykin, A.J., Morris, J.C., Shaw, L.M., Liu, E., Montine, T., Thomas, R.G., Donohue, M., Walter, S., Gessert, D., Sather, T., Jiminez, G., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, .... |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2022 |
| Collection: |
Murdoch University: Murdoch Research Repository |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://researchrepository.murdoch.edu.au/id/eprint/64712/; full_text_status:public |
| Availability: |
https://researchrepository.murdoch.edu.au/id/eprint/64712/ |
| Rights: |
© 2022 The Authors. |
| Accession Number: |
edsbas.64B38D0B |
| Database: |
BASE |