DNA methylation predicts age and provides insight into exceptional longevity of bats

Gerald S. Wilkinson; Danielle M. Adams; Amin Haghani; Ake T. Lu; Joseph Zoller; Charles E. Breeze; Bryan D. Arnold; Hope C. Ball; Gerald G. Carter; Lisa Noelle Cooper; Dina K. N. Dechmann; Paolo Devanna; Nicolas J. Fasel; Alexander V. Galazyuk; Linus Günther; Edward Hurme; Gareth Jones; Mirjam Knörnschild; Ella Z. Lattenkamp; Caesar Z. Li; Frieder Mayer; Josephine A. Reinhardt; Rodrigo A. Medellin; Martina Nagy; Brian Pope; Megan L. Power; Roger D. Ransome; Emma C. Teeling; Sonja C. Vernes; Daniel Zamora-Mejías; Joshua Zhang; Paul A. Faure; Lucas J. Greville; Steve Horvath

doi:10.1038/s41467-021-21900-2

DNA methylation predicts age and provides insight into exceptional longevity of bats

Gerald S. Wilkinson^*, Danielle M. Adams, Amin Haghani, Ake T. Lu, Joseph Zoller, Charles E. Breeze, Bryan D. Arnold, Hope C. Ball, Gerald G. Carter, Lisa Noelle Cooper, Dina K. N. Dechmann, Paolo Devanna, Nicolas J. Fasel, Alexander V. Galazyuk, Linus Günther, Edward Hurme, Gareth Jones, Mirjam Knörnschild, Ella Z. Lattenkamp, Caesar Z. LiFrieder Mayer, Josephine A. Reinhardt, Rodrigo A. Medellin, Martina Nagy, Brian Pope, Megan L. Power, Roger D. Ransome, Emma C. Teeling, Sonja C. Vernes, Daniel Zamora-Mejías, Joshua Zhang, Paul A. Faure, Lucas J. Greville, Steve Horvath^*

^*Corresponding author for this work

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

Abstract

Exceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity. We demonstrate that DNAm accurately predicts chronological age. Across species, longevity is negatively associated with the rate of DNAm change at age-associated sites. Furthermore, analysis of several bat genomes reveals that hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results from augmented immune response and cancer suppression.

Original language	English
Article number	1615
Number of pages	13
Journal	Nature Communications
Volume	12
DOIs	https://doi.org/10.1038/s41467-021-21900-2
Publication status	Published - 12 Mar 2021

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SDG 3 Good Health and Well-being

Keywords

Ageing
Epigenomics
Methylation analysis

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Wilkinson, G. S., Adams, D. M., Haghani, A., Lu, A. T., Zoller, J., Breeze, C. E., Arnold, B. D., Ball, H. C., Carter, G. G., Cooper, L. N., Dechmann, D. K. N., Devanna, P., Fasel, N. J., Galazyuk, A. V., Günther, L., Hurme, E., Jones, G., Knörnschild, M., Lattenkamp, E. Z., ... Horvath, S. (2021). DNA methylation predicts age and provides insight into exceptional longevity of bats. Nature Communications, 12, Article 1615. https://doi.org/10.1038/s41467-021-21900-2

@article{156a98c82457408cbe6d7611f1826ca9,

title = "DNA methylation predicts age and provides insight into exceptional longevity of bats",

abstract = "Exceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity. We demonstrate that DNAm accurately predicts chronological age. Across species, longevity is negatively associated with the rate of DNAm change at age-associated sites. Furthermore, analysis of several bat genomes reveals that hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results from augmented immune response and cancer suppression.",

keywords = "Ageing, Epigenomics, Methylation analysis",

author = "Wilkinson, \{Gerald S.\} and Adams, \{Danielle M.\} and Amin Haghani and Lu, \{Ake T.\} and Joseph Zoller and Breeze, \{Charles E.\} and Arnold, \{Bryan D.\} and Ball, \{Hope C.\} and Carter, \{Gerald G.\} and Cooper, \{Lisa Noelle\} and Dechmann, \{Dina K. N.\} and Paolo Devanna and Fasel, \{Nicolas J.\} and Galazyuk, \{Alexander V.\} and Linus G{\"u}nther and Edward Hurme and Gareth Jones and Mirjam Kn{\"o}rnschild and Lattenkamp, \{Ella Z.\} and Li, \{Caesar Z.\} and Frieder Mayer and Reinhardt, \{Josephine A.\} and Medellin, \{Rodrigo A.\} and Martina Nagy and Brian Pope and Power, \{Megan L.\} and Ransome, \{Roger D.\} and Teeling, \{Emma C.\} and Vernes, \{Sonja C.\} and Daniel Zamora-Mej{\'i}as and Joshua Zhang and Faure, \{Paul A.\} and Greville, \{Lucas J.\} and Steve Horvath",

note = "This work was supported by a Paul G. Allen Frontiers Group grant to S.H., the University of Maryland, College of Computer, Mathematical and Natural Sciences to G.S.W., an Irish Research Council Consolidator Laureate Award to E.C.T., a UKRI Future Leaders Fellowship (MR/T021985/1) to S.C.V. and a Discovery Grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada to P.A.F. S.C.V. and P.D. were supported by a Max Planck Research Group awarded to S.C.V. by the Max Planck Gesellschaft, and S.C.V. and E.Z.L. were supported by a Human Frontiers Science Program Grant (RGP0058/2016) awarded to S.C.V. L.J.G. was supported by an NSERC PGS-D scholarship. ",

year = "2021",

month = mar,

day = "12",

doi = "10.1038/s41467-021-21900-2",

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

}

Wilkinson, GS, Adams, DM, Haghani, A, Lu, AT, Zoller, J, Breeze, CE, Arnold, BD, Ball, HC, Carter, GG, Cooper, LN, Dechmann, DKN, Devanna, P, Fasel, NJ, Galazyuk, AV, Günther, L, Hurme, E, Jones, G, Knörnschild, M, Lattenkamp, EZ, Li, CZ, Mayer, F, Reinhardt, JA, Medellin, RA, Nagy, M, Pope, B, Power, ML, Ransome, RD, Teeling, EC, Vernes, SC, Zamora-Mejías, D, Zhang, J, Faure, PA, Greville, LJ & Horvath, S 2021, 'DNA methylation predicts age and provides insight into exceptional longevity of bats', Nature Communications, vol. 12, 1615. https://doi.org/10.1038/s41467-021-21900-2

TY - JOUR

T1 - DNA methylation predicts age and provides insight into exceptional longevity of bats

AU - Wilkinson, Gerald S.

AU - Adams, Danielle M.

AU - Haghani, Amin

AU - Lu, Ake T.

AU - Zoller, Joseph

AU - Breeze, Charles E.

AU - Arnold, Bryan D.

AU - Ball, Hope C.

AU - Carter, Gerald G.

AU - Cooper, Lisa Noelle

AU - Dechmann, Dina K. N.

AU - Devanna, Paolo

AU - Fasel, Nicolas J.

AU - Galazyuk, Alexander V.

AU - Günther, Linus

AU - Hurme, Edward

AU - Jones, Gareth

AU - Knörnschild, Mirjam

AU - Lattenkamp, Ella Z.

AU - Li, Caesar Z.

AU - Mayer, Frieder

AU - Reinhardt, Josephine A.

AU - Medellin, Rodrigo A.

AU - Nagy, Martina

AU - Pope, Brian

AU - Power, Megan L.

AU - Ransome, Roger D.

AU - Teeling, Emma C.

AU - Vernes, Sonja C.

AU - Zamora-Mejías, Daniel

AU - Zhang, Joshua

AU - Faure, Paul A.

AU - Greville, Lucas J.

AU - Horvath, Steve

N1 - This work was supported by a Paul G. Allen Frontiers Group grant to S.H., the University of Maryland, College of Computer, Mathematical and Natural Sciences to G.S.W., an Irish Research Council Consolidator Laureate Award to E.C.T., a UKRI Future Leaders Fellowship (MR/T021985/1) to S.C.V. and a Discovery Grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada to P.A.F. S.C.V. and P.D. were supported by a Max Planck Research Group awarded to S.C.V. by the Max Planck Gesellschaft, and S.C.V. and E.Z.L. were supported by a Human Frontiers Science Program Grant (RGP0058/2016) awarded to S.C.V. L.J.G. was supported by an NSERC PGS-D scholarship.

PY - 2021/3/12

Y1 - 2021/3/12

N2 - Exceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity. We demonstrate that DNAm accurately predicts chronological age. Across species, longevity is negatively associated with the rate of DNAm change at age-associated sites. Furthermore, analysis of several bat genomes reveals that hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results from augmented immune response and cancer suppression.

AB - Exceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity. We demonstrate that DNAm accurately predicts chronological age. Across species, longevity is negatively associated with the rate of DNAm change at age-associated sites. Furthermore, analysis of several bat genomes reveals that hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results from augmented immune response and cancer suppression.

KW - Ageing

KW - Epigenomics

KW - Methylation analysis

UR - https://www.scopus.com/pages/publications/85102504493

U2 - 10.1038/s41467-021-21900-2

DO - 10.1038/s41467-021-21900-2

M3 - Article

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

M1 - 1615

ER -

DNA methylation predicts age and provides insight into exceptional longevity of bats

Abstract

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Keywords

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