Universal DNA methylation age across mammalian tissues

Lu, A.T., Fei, Z., Haghani, A., Robeck, T.R., Zoller, J.A., Li, C.Z., Lowe, R., Yan, Q., Zhang, J., Vu, H., Ablaeva, J., Acosta-Rodriguez, V.A., Adams, D.M., Almunia, J., Aloysius, A., Ardehali, R., Arneson, A., Baker, C.S., Banks, G. ORCID: 0000-0002-8647-667X, Belov, K., Bennett, N.C., Black, P., Blumstein, D.T., Bors, E.K., Breeze, C.E., Brooke, R.T., Brown, J.L., Carter, G.G., Caulton, A., Cavin, J.M., Chakrabarti, L., Chatzistamou, I., Chen, H., Cheng, K., Chiavellini, P., Choi, O.W., Clarke, S.M., Cooper, L.N., Cossette, M.L., Day, J., DeYoung, J., DiRocco, S., Dold, C., Ehmke, E.E., Emmons, C.K., Emmrich, S., Erbay, E., Erlacher-Reid, C., Faulkes, C.G., Ferguson, S.H., Finno, C.J., Flower, J.E., Gaillard, J.M., Garde, E., Gerber, L., Gladyshev, V.N., Gorbunova, V., Goya, R.G., Grant, M.J., Green, C.B., Hales, E.N., Hanson, M.B., Hart, D.W., Haulena, M., Herrick, K., Hogan, A.N., Hogg, C.J., Hore, T.A., Huang, T., Izpisua Belmonte, J.C., Jasinska, A.J., Jones, G., Jourdain, E., Kashpur, O., Katcher, H., Katsumata, E., Kaza, V., Kiaris, H., Kobor, M.S., Kordowitzki, P., Koski, W.R., Krützen, M., Kwon, S.B., Larison, B., Lee, S.G., Lehmann, M., Lemaitre, J.F., Levine, A.J., Li, C., Li, X., Lim, A.R., Lin, D.T.S., Lindemann, D.M., Little, T.J., Macoretta, N., Maddox, D., Matkin, C.O., Mattison, J.A., McClure, M., Mergl, J., Meudt, J.J., Montano, G.A., Mozhui, K., Munshi-South, J., Naderi, A., Nagy, M., Narayan, P., Nathanielsz, P.W., Nguyen, N.B., Niehrs, C., O’Brien, J.K., O’Tierney Ginn, P., Odom, D.T., Ophir, A.G., Osborn, S., Ostrander, E.A., Parsons, K.M., Paul, K.C., Pellegrini, M., Peters, K.J., Pedersen, A.B., Petersen, J.L., Pietersen, D.W., Pinho, G.M., Plassais, J., Poganik, J.R., Prado, N.A., Reddy, P., Rey, B., Ritz, B.R., Robbins, J., Rodriguez, M., Russell, J., Rydkina, E., Sailer, L.L., Salmon, A.B., Sanghavi, A., Schachtschneider, K.M., Schmitt, D., Schmitt, T., Schomacher, L., Schook, L.B., Sears, K.E., Seifert, A.W., Seluanov, A., Shafer, A.B.A., Shanmuganayagam, D., Shindyapina, A.V., Simmons, M., Singh, K., Sinha, I., Slone, J., Snell, R.G., Soltanmaohammadi, E., Spangler, M.L., Spriggs, M.C., Staggs, L., Stedman, N., Steinman, K.J., Stewart, D.T., Sugrue, V.J., Szladovits, B., Takahashi, J.S., Takasugi, M., Teeling, E.C., Thompson, M.J., Van Bonn, B., Vernes, S.C., Villar, D., Vinters, H.V., Wallingford, M.C., Wang, N., Wayne, R.K., Wilkinson, G.S., Williams, C.K., Williams, R.W., Yang, X.W., Yao, M., Young, B.G., Zhang, B., Zhang, Z., Zhao, P., Zhao, Y., Zhou, W., Zimmermann, J., Ernst, J., Raj, K. and Horvath, S., 2023. Universal DNA methylation age across mammalian tissues. Nature Aging. ISSN 2662-8465

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Abstract

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.

Item Type:	Journal article
Publication Title:	Nature Aging
Creators:	Lu, A.T., Fei, Z., Haghani, A., Robeck, T.R., Zoller, J.A., Li, C.Z., Lowe, R., Yan, Q., Zhang, J., Vu, H., Ablaeva, J., Acosta-Rodriguez, V.A., Adams, D.M., Almunia, J., Aloysius, A., Ardehali, R., Arneson, A., Baker, C.S., Banks, G., Belov, K., Bennett, N.C., Black, P., Blumstein, D.T., Bors, E.K., Breeze, C.E., Brooke, R.T., Brown, J.L., Carter, G.G., Caulton, A., Cavin, J.M., Chakrabarti, L., Chatzistamou, I., Chen, H., Cheng, K., Chiavellini, P., Choi, O.W., Clarke, S.M., Cooper, L.N., Cossette, M.L., Day, J., DeYoung, J., DiRocco, S., Dold, C., Ehmke, E.E., Emmons, C.K., Emmrich, S., Erbay, E., Erlacher-Reid, C., Faulkes, C.G., Ferguson, S.H., Finno, C.J., Flower, J.E., Gaillard, J.M., Garde, E., Gerber, L., Gladyshev, V.N., Gorbunova, V., Goya, R.G., Grant, M.J., Green, C.B., Hales, E.N., Hanson, M.B., Hart, D.W., Haulena, M., Herrick, K., Hogan, A.N., Hogg, C.J., Hore, T.A., Huang, T., Izpisua Belmonte, J.C., Jasinska, A.J., Jones, G., Jourdain, E., Kashpur, O., Katcher, H., Katsumata, E., Kaza, V., Kiaris, H., Kobor, M.S., Kordowitzki, P., Koski, W.R., Krützen, M., Kwon, S.B., Larison, B., Lee, S.G., Lehmann, M., Lemaitre, J.F., Levine, A.J., Li, C., Li, X., Lim, A.R., Lin, D.T.S., Lindemann, D.M., Little, T.J., Macoretta, N., Maddox, D., Matkin, C.O., Mattison, J.A., McClure, M., Mergl, J., Meudt, J.J., Montano, G.A., Mozhui, K., Munshi-South, J., Naderi, A., Nagy, M., Narayan, P., Nathanielsz, P.W., Nguyen, N.B., Niehrs, C., O’Brien, J.K., O’Tierney Ginn, P., Odom, D.T., Ophir, A.G., Osborn, S., Ostrander, E.A., Parsons, K.M., Paul, K.C., Pellegrini, M., Peters, K.J., Pedersen, A.B., Petersen, J.L., Pietersen, D.W., Pinho, G.M., Plassais, J., Poganik, J.R., Prado, N.A., Reddy, P., Rey, B., Ritz, B.R., Robbins, J., Rodriguez, M., Russell, J., Rydkina, E., Sailer, L.L., Salmon, A.B., Sanghavi, A., Schachtschneider, K.M., Schmitt, D., Schmitt, T., Schomacher, L., Schook, L.B., Sears, K.E., Seifert, A.W., Seluanov, A., Shafer, A.B.A., Shanmuganayagam, D., Shindyapina, A.V., Simmons, M., Singh, K., Sinha, I., Slone, J., Snell, R.G., Soltanmaohammadi, E., Spangler, M.L., Spriggs, M.C., Staggs, L., Stedman, N., Steinman, K.J., Stewart, D.T., Sugrue, V.J., Szladovits, B., Takahashi, J.S., Takasugi, M., Teeling, E.C., Thompson, M.J., Van Bonn, B., Vernes, S.C., Villar, D., Vinters, H.V., Wallingford, M.C., Wang, N., Wayne, R.K., Wilkinson, G.S., Williams, C.K., Williams, R.W., Yang, X.W., Yao, M., Young, B.G., Zhang, B., Zhang, Z., Zhao, P., Zhao, Y., Zhou, W., Zimmermann, J., Ernst, J., Raj, K. and Horvath, S.
Publisher:	Springer Science and Business Media LLC
Date:	10 August 2023
ISSN:	2662-8465
Identifiers:	Number Type 10.1038/s43587-023-00462-6 DOI 1793693 Other
Rights:	© The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	31 Aug 2023 15:00
Last Modified:	31 Aug 2023 15:00
URI:	https://irep.ntu.ac.uk/id/eprint/49628

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