Universal DNA methylation age across mammalian tissues

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

doi:10.1038/s43587-023-00462-6

Universal DNA methylation age across mammalian tissues

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

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1144-1166
Number of pages	23
Journal	Nature Aging
Volume	3
Issue number	9
DOIs	https://doi.org/10.1038/s43587-023-00462-6
State	Published - Sep 2023
Externally published	Yes

ASJC Scopus subject areas

Neuroscience (miscellaneous)
Aging
Geriatrics and Gerontology

Access to Document

10.1038/s43587-023-00462-6

Cite this

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., ... Horvath, S. (2023). Universal DNA methylation age across mammalian tissues. Nature Aging, 3(9), 1144-1166. https://doi.org/10.1038/s43587-023-00462-6

Lu, AT, Fei, Z, Haghani, A, Robeck, TR, Zoller, JA, Li, CZ, Lowe, R, Yan, Q, Zhang, J, Vu, H, Ablaeva, J, Acosta-Rodriguez, VA, Adams, DM, Almunia, J, Aloysius, A, Ardehali, R, Arneson, A, Baker, CS, Banks, G, Belov, K, Bennett, NC, Black, P, Blumstein, DT, Bors, EK, Breeze, CE, Brooke, RT, Brown, JL, Carter, GG, Caulton, A, Cavin, JM, Chakrabarti, L, Chatzistamou, I, Chen, H, Cheng, K, Chiavellini, P, Choi, OW, Clarke, SM, Cooper, LN, Cossette, ML, Day, J, DeYoung, J, DiRocco, S, Dold, C, Ehmke, EE, Emmons, CK, Emmrich, S, Erbay, E, Erlacher-Reid, C, Faulkes, CG, Ferguson, SH, Finno, CJ, Flower, JE, Gaillard, JM, Garde, E, Gerber, L, Gladyshev, VN, Gorbunova, V, Goya, RG, Grant, MJ, Green, CB, Hales, EN, Hanson, MB, Hart, DW, Haulena, M, Herrick, K, Hogan, AN, Hogg, CJ, Hore, TA, Huang, T, Izpisua Belmonte, JC, Jasinska, AJ, Jones, G, Jourdain, E, Kashpur, O, Katcher, H, Katsumata, E, Kaza, V, Kiaris, H, Kobor, MS, Kordowitzki, P, Koski, WR, Krützen, M, Kwon, SB, Larison, B, Lee, SG, Lehmann, M, Lemaitre, JF, Levine, AJ, Li, C, Li, X, Lim, AR, Lin, DTS, Lindemann, DM, Little, TJ, Macoretta, N, Maddox, D, Matkin, CO, Mattison, JA, McClure, M, Mergl, J, Meudt, JJ, Montano, GA, Mozhui, K, Munshi-South, J, Naderi, A, Nagy, M, Narayan, P, Nathanielsz, PW, Nguyen, NB, Niehrs, C, O’Brien, JK, O’Tierney Ginn, P, Odom, DT, Ophir, AG, Osborn, S, Ostrander, EA, Parsons, KM, Paul, KC, Pellegrini, M, Peters, KJ, Pedersen, AB, Petersen, JL, Pietersen, DW, Pinho, GM, Plassais, J, Poganik, JR, Prado, NA, Reddy, P, Rey, B, Ritz, BR, Robbins, J, Rodriguez, M, Russell, J, Rydkina, E, Sailer, LL, Salmon, AB, Sanghavi, A, Schachtschneider, KM, Schmitt, D, Schmitt, T, Schomacher, L, Schook, LB, Sears, KE, Seifert, AW, Seluanov, A, Shafer, ABA, Shanmuganayagam, D, Shindyapina, AV, Simmons, M, Singh, K, Sinha, I, Slone, J, Snell, RG, Soltanmaohammadi, E, Spangler, ML, Spriggs, MC, Staggs, L, Stedman, N, Steinman, KJ, Stewart, DT, Sugrue, VJ, Szladovits, B, Takahashi, JS, Takasugi, M, Teeling, EC, Thompson, MJ, Van Bonn, B, Vernes, SC, Villar, D, Vinters, HV, Wallingford, MC, Wang, N, Wayne, RK, Wilkinson, GS, Williams, CK, Williams, RW, Yang, XW, Yao, M, Young, BG, Zhang, B, Zhang, Z, Zhao, P, Zhao, Y, Zhou, W, Zimmermann, J, Ernst, J, Raj, K & Horvath, S 2023, 'Universal DNA methylation age across mammalian tissues', Nature Aging, vol. 3, no. 9, pp. 1144-1166. https://doi.org/10.1038/s43587-023-00462-6

@article{c65850cae523473188aaf66af1353f7a,

title = "Universal DNA methylation age across mammalian tissues",

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.",

author = "Lu, {A. T.} and Z. Fei and A. Haghani and Robeck, {T. R.} and Zoller, {J. A.} and Li, {C. Z.} and R. Lowe and Q. Yan and J. Zhang and H. Vu and J. Ablaeva and Acosta-Rodriguez, {V. A.} and Adams, {D. M.} and J. Almunia and A. Aloysius and R. Ardehali and A. Arneson and Baker, {C. S.} and G. Banks and K. Belov and Bennett, {N. C.} and P. Black and Blumstein, {D. T.} and Bors, {E. K.} and Breeze, {C. E.} and Brooke, {R. T.} and Brown, {J. L.} and Carter, {G. G.} and A. Caulton and Cavin, {J. M.} and L. Chakrabarti and I. Chatzistamou and H. Chen and K. Cheng and P. Chiavellini and Choi, {O. W.} and Clarke, {S. M.} and Cooper, {L. N.} and Cossette, {M. L.} and J. Day and J. DeYoung and S. DiRocco and C. Dold and Ehmke, {E. E.} and Emmons, {C. K.} and S. Emmrich and E. Erbay and C. Erlacher-Reid and Faulkes, {C. G.} and Ferguson, {S. H.} and Finno, {C. J.} and Flower, {J. E.} and Gaillard, {J. M.} and E. Garde and L. Gerber and Gladyshev, {V. N.} and V. Gorbunova and Goya, {R. G.} and Grant, {M. J.} and Green, {C. B.} and Hales, {E. N.} and Hanson, {M. B.} and Hart, {D. W.} and M. Haulena and K. Herrick and Hogan, {A. N.} and Hogg, {C. J.} and Hore, {T. A.} and T. Huang and {Izpisua Belmonte}, {J. C.} and Jasinska, {A. J.} and G. Jones and E. Jourdain and O. Kashpur and H. Katcher and E. Katsumata and V. Kaza and H. Kiaris and Kobor, {M. S.} and P. Kordowitzki and Koski, {W. R.} and M. Kr{\"u}tzen and Kwon, {S. B.} and B. Larison and Lee, {S. G.} and M. Lehmann and Lemaitre, {J. F.} and Levine, {A. J.} and C. Li and X. Li and Lim, {A. R.} and Lin, {D. T.S.} and Lindemann, {D. M.} and Little, {T. J.} and N. Macoretta and D. Maddox and Matkin, {C. O.} and Mattison, {J. A.} and M. McClure and J. Mergl and Meudt, {J. J.} and Montano, {G. A.} and K. Mozhui and J. Munshi-South and A. Naderi and M. Nagy and P. Narayan and Nathanielsz, {P. W.} and Nguyen, {N. B.} and C. Niehrs and O{\textquoteright}Brien, {J. K.} and {O{\textquoteright}Tierney Ginn}, P. and Odom, {D. T.} and Ophir, {A. G.} and S. Osborn and Ostrander, {E. A.} and Parsons, {K. M.} and Paul, {K. C.} and M. Pellegrini and Peters, {K. J.} and Pedersen, {A. B.} and Petersen, {J. L.} and Pietersen, {D. W.} and Pinho, {G. M.} and J. Plassais and Poganik, {J. R.} and Prado, {N. A.} and P. Reddy and B. Rey and Ritz, {B. R.} and J. Robbins and M. Rodriguez and J. Russell and E. Rydkina and Sailer, {L. L.} and Salmon, {A. B.} and A. Sanghavi and Schachtschneider, {K. M.} and D. Schmitt and T. Schmitt and L. Schomacher and Schook, {L. B.} and Sears, {K. E.} and Seifert, {A. W.} and A. Seluanov and Shafer, {A. B.A.} and D. Shanmuganayagam and Shindyapina, {A. V.} and M. Simmons and K. Singh and I. Sinha and J. Slone and Snell, {R. G.} and E. Soltanmaohammadi and Spangler, {M. L.} and Spriggs, {M. C.} and L. Staggs and N. Stedman and Steinman, {K. J.} and Stewart, {D. T.} and Sugrue, {V. J.} and B. Szladovits and Takahashi, {J. S.} and M. Takasugi and Teeling, {E. C.} and Thompson, {M. J.} and {Van Bonn}, B. and Vernes, {S. C.} and D. Villar and Vinters, {H. V.} and Wallingford, {M. C.} and N. Wang and Wayne, {R. K.} and Wilkinson, {G. S.} and Williams, {C. K.} and Williams, {R. W.} and Yang, {X. W.} and M. Yao and Young, {B. G.} and B. Zhang and Z. Zhang and P. Zhao and Y. Zhao and W. Zhou and J. Zimmermann and J. Ernst and K. Raj and S. Horvath",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = sep,

doi = "10.1038/s43587-023-00462-6",

language = "English (US)",

volume = "3",

pages = "1144--1166",

journal = "Nature Aging",

issn = "2662-8465",

publisher = "Springer",

number = "9",

}

TY - JOUR

T1 - Universal DNA methylation age across mammalian tissues

AU - Lu, A. T.

AU - Fei, Z.

AU - Haghani, A.

AU - Robeck, T. R.

AU - Zoller, J. A.

AU - Li, C. Z.

AU - Lowe, R.

AU - Yan, Q.

AU - Zhang, J.

AU - Vu, H.

AU - Ablaeva, J.

AU - Acosta-Rodriguez, V. A.

AU - Adams, D. M.

AU - Almunia, J.

AU - Aloysius, A.

AU - Ardehali, R.

AU - Arneson, A.

AU - Baker, C. S.

AU - Banks, G.

AU - Belov, K.

AU - Bennett, N. C.

AU - Black, P.

AU - Blumstein, D. T.

AU - Bors, E. K.

AU - Breeze, C. E.

AU - Brooke, R. T.

AU - Brown, J. L.

AU - Carter, G. G.

AU - Caulton, A.

AU - Cavin, J. M.

AU - Chakrabarti, L.

AU - Chatzistamou, I.

AU - Chen, H.

AU - Cheng, K.

AU - Chiavellini, P.

AU - Choi, O. W.

AU - Clarke, S. M.

AU - Cooper, L. N.

AU - Cossette, M. L.

AU - Day, J.

AU - DeYoung, J.

AU - DiRocco, S.

AU - Dold, C.

AU - Ehmke, E. E.

AU - Emmons, C. K.

AU - Emmrich, S.

AU - Erbay, E.

AU - Erlacher-Reid, C.

AU - Faulkes, C. G.

AU - Ferguson, S. H.

AU - Finno, C. J.

AU - Flower, J. E.

AU - Gaillard, J. M.

AU - Garde, E.

AU - Gerber, L.

AU - Gladyshev, V. N.

AU - Gorbunova, V.

AU - Goya, R. G.

AU - Grant, M. J.

AU - Green, C. B.

AU - Hales, E. N.

AU - Hanson, M. B.

AU - Hart, D. W.

AU - Haulena, M.

AU - Herrick, K.

AU - Hogan, A. N.

AU - Hogg, C. J.

AU - Hore, T. A.

AU - Huang, T.

AU - Izpisua Belmonte, J. C.

AU - Jasinska, A. J.

AU - Jones, G.

AU - Jourdain, E.

AU - Kashpur, O.

AU - Katcher, H.

AU - Katsumata, E.

AU - Kaza, V.

AU - Kiaris, H.

AU - Kobor, M. S.

AU - Kordowitzki, P.

AU - Koski, W. R.

AU - Krützen, M.

AU - Kwon, S. B.

AU - Larison, B.

AU - Lee, S. G.

AU - Lehmann, M.

AU - Lemaitre, J. F.

AU - Levine, A. J.

AU - Li, C.

AU - Li, X.

AU - Lim, A. R.

AU - Lin, D. T.S.

AU - Lindemann, D. M.

AU - Little, T. J.

AU - Macoretta, N.

AU - Maddox, D.

AU - Matkin, C. O.

AU - Mattison, J. A.

AU - McClure, M.

AU - Mergl, J.

AU - Meudt, J. J.

AU - Montano, G. A.

AU - Mozhui, K.

AU - Munshi-South, J.

AU - Naderi, A.

AU - Nagy, M.

AU - Narayan, P.

AU - Nathanielsz, P. W.

AU - Nguyen, N. B.

AU - Niehrs, C.

AU - O’Brien, J. K.

AU - O’Tierney Ginn, P.

AU - Odom, D. T.

AU - Ophir, A. G.

AU - Osborn, S.

AU - Ostrander, E. A.

AU - Parsons, K. M.

AU - Paul, K. C.

AU - Pellegrini, M.

AU - Peters, K. J.

AU - Pedersen, A. B.

AU - Petersen, J. L.

AU - Pietersen, D. W.

AU - Pinho, G. M.

AU - Plassais, J.

AU - Poganik, J. R.

AU - Prado, N. A.

AU - Reddy, P.

AU - Rey, B.

AU - Ritz, B. R.

AU - Robbins, J.

AU - Rodriguez, M.

AU - Russell, J.

AU - Rydkina, E.

AU - Sailer, L. L.

AU - Salmon, A. B.

AU - Sanghavi, A.

AU - Schachtschneider, K. M.

AU - Schmitt, D.

AU - Schmitt, T.

AU - Schomacher, L.

AU - Schook, L. B.

AU - Sears, K. E.

AU - Seifert, A. W.

AU - Seluanov, A.

AU - Shafer, A. B.A.

AU - Shanmuganayagam, D.

AU - Shindyapina, A. V.

AU - Simmons, M.

AU - Singh, K.

AU - Sinha, I.

AU - Slone, J.

AU - Snell, R. G.

AU - Soltanmaohammadi, E.

AU - Spangler, M. L.

AU - Spriggs, M. C.

AU - Staggs, L.

AU - Stedman, N.

AU - Steinman, K. J.

AU - Stewart, D. T.

AU - Sugrue, V. J.

AU - Szladovits, B.

AU - Takahashi, J. S.

AU - Takasugi, M.

AU - Teeling, E. C.

AU - Thompson, M. J.

AU - Van Bonn, B.

AU - Vernes, S. C.

AU - Villar, D.

AU - Vinters, H. V.

AU - Wallingford, M. C.

AU - Wang, N.

AU - Wayne, R. K.

AU - Wilkinson, G. S.

AU - Williams, C. K.

AU - Williams, R. W.

AU - Yang, X. W.

AU - Yao, M.

AU - Young, B. G.

AU - Zhang, B.

AU - Zhang, Z.

AU - Zhao, P.

AU - Zhao, Y.

AU - Zhou, W.

AU - Zimmermann, J.

AU - Ernst, J.

AU - Raj, K.

AU - Horvath, S.

PY - 2023/9

Y1 - 2023/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85165881383&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85165881383&partnerID=8YFLogxK

U2 - 10.1038/s43587-023-00462-6

DO - 10.1038/s43587-023-00462-6

M3 - Article

C2 - 37563227

AN - SCOPUS:85165881383

SN - 2662-8465

VL - 3

SP - 1144

EP - 1166

JO - Nature Aging

JF - Nature Aging

IS - 9

ER -

Universal DNA methylation age across mammalian tissues

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