Making sense of the ageing methylome

doi:10.1038/s41576-022-00477-6

Review

. 2022 Oct;23(10):585-605.

doi: 10.1038/s41576-022-00477-6. Epub 2022 May 2.

Making sense of the ageing methylome

Kirsten Seale¹, Steve Horvath^{2

3}, Andrew Teschendorff^{4

5}, Nir Eynon⁶, Sarah Voisin⁷

Affiliations

¹ Institute for Health and Sport (iHeS), Victoria University, Footscray, Melbourne, Victoria, Australia.
² Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
³ Altos Labs, San Diego, CA, USA.
⁴ CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
⁵ UCL Cancer Institute, University College London, London, UK.
⁶ Institute for Health and Sport (iHeS), Victoria University, Footscray, Melbourne, Victoria, Australia. nir.eynon@vu.edu.au.
⁷ Institute for Health and Sport (iHeS), Victoria University, Footscray, Melbourne, Victoria, Australia. sarah.voisin@vu.edu.au.

PMID: 35501397
DOI: 10.1038/s41576-022-00477-6

Review

Making sense of the ageing methylome

Kirsten Seale et al. Nat Rev Genet. 2022 Oct.

. 2022 Oct;23(10):585-605.

doi: 10.1038/s41576-022-00477-6. Epub 2022 May 2.

Authors

Kirsten Seale¹, Steve Horvath^{2

3}, Andrew Teschendorff^{4

5}, Nir Eynon⁶, Sarah Voisin⁷

Affiliations

¹ Institute for Health and Sport (iHeS), Victoria University, Footscray, Melbourne, Victoria, Australia.
² Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
³ Altos Labs, San Diego, CA, USA.
⁴ CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
⁵ UCL Cancer Institute, University College London, London, UK.
⁶ Institute for Health and Sport (iHeS), Victoria University, Footscray, Melbourne, Victoria, Australia. nir.eynon@vu.edu.au.
⁷ Institute for Health and Sport (iHeS), Victoria University, Footscray, Melbourne, Victoria, Australia. sarah.voisin@vu.edu.au.

PMID: 35501397
DOI: 10.1038/s41576-022-00477-6

Abstract

Over time, the human DNA methylation landscape accrues substantial damage, which has been associated with a broad range of age-related diseases, including cardiovascular disease and cancer. Various age-related DNA methylation changes have been described, including at the level of individual CpGs, such as differential and variable methylation, and at the level of the whole methylome, including entropy and correlation networks. Here, we review these changes in the ageing methylome as well as the statistical tools that can be used to quantify them. We detail the evidence linking DNA methylation to ageing phenotypes and the longevity strategies aimed at altering both DNA methylation patterns and machinery to extend healthspan and lifespan. Lastly, we discuss theories on the mechanistic causes of epigenetic ageing.

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References

1. Seals, D. R., Justice, J. N. & Larocca, T. J. Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity. J. Physiol. 594, 2001–2024 (2016). - PubMed - DOI
1. Petsko, G. A. A seat at the table. Genome Biol. 9, 113 (2008). - PubMed - PMC - DOI
1. Partridge, L., Deelen, J. & Slagboom, P. E. Facing up to the global challenges of ageing. Nature 561, 45–56 (2018). - PubMed - DOI
1. Crimmins, E. M. Lifespan and healthspan: past, present, and promise. Gerontologist 55, 901–911 (2015). - PubMed - PMC - DOI
1. Harper, S. Economic and social implications of aging societies. Science 346, 587–591 (2014). - PubMed - DOI

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[1] Seals, D. R., Justice, J. N. & Larocca, T. J. Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity. J. Physiol. 594, 2001–2024 (2016). - PubMed - DOI

[2] Seals, D. R., Justice, J. N. & Larocca, T. J. Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity. J. Physiol. 594, 2001–2024 (2016). - PubMed - DOI

[3] Petsko, G. A. A seat at the table. Genome Biol. 9, 113 (2008). - PubMed - PMC - DOI

[4] Petsko, G. A. A seat at the table. Genome Biol. 9, 113 (2008). - PubMed - PMC - DOI

[5] Partridge, L., Deelen, J. & Slagboom, P. E. Facing up to the global challenges of ageing. Nature 561, 45–56 (2018). - PubMed - DOI

[6] Partridge, L., Deelen, J. & Slagboom, P. E. Facing up to the global challenges of ageing. Nature 561, 45–56 (2018). - PubMed - DOI

[7] Crimmins, E. M. Lifespan and healthspan: past, present, and promise. Gerontologist 55, 901–911 (2015). - PubMed - PMC - DOI

[8] Crimmins, E. M. Lifespan and healthspan: past, present, and promise. Gerontologist 55, 901–911 (2015). - PubMed - PMC - DOI

[9] Harper, S. Economic and social implications of aging societies. Science 346, 587–591 (2014). - PubMed - DOI

[10] Harper, S. Economic and social implications of aging societies. Science 346, 587–591 (2014). - PubMed - DOI

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Making sense of the ageing methylome

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