Cited by 68Telomeres, Telomerase, and SenescenceEpigenetics and DNA MethylationGenetics, Aging, and Longevity in Model Organisms

Epigenetic ageing is distinct from senescence-mediated ageing and is not prevented by telomerase expression

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Kabacik, Sylwia, Horvath, Steve, Cohen, Howard, Raj, Kenneth·2018·Aging

Abstract

, we interrogated the relationship between epigenetic ageing and telomerase activity. Although hTERT did not induce any perceptible change to the rate of epigenetic ageing, hTERT-expressing cells, which bypassed senescence, continued to age epigenetically. Employment of hTERT mutants revealed that neither telomere synthesis nor immortalisation is necessary for the continued increase in epigenetic age by these cells. Instead, the extension of their lifespan is sufficient to support continued epigenetic ageing of the cell. These characteristics, observed in cells from numerous donors and cell types, reveal epigenetic ageing to be distinct from replicative senescence. Hence, while re-activation of hTERT may stave off physical manifestation of ageing through avoidance of replicative senescence, it would have little impact on epigenetic ageing which continues in spite of telomerase activity.

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Authors
Kabacik, S., Horvath, S., Cohen, H., & Raj, K.
Affiliations
  • Public Health England (GB)
  • University of California, Los Angeles (US)
  • Elizabeth House Medical Practice, Warlingham, Surrey CR6 9LF, United Kingdom
Corresponding author
Kabacik, Sylwia
Venue
Aging
Published
2018-10-17
Volume
10
Issue
10
Pages
2800-2815
ISSN
1945-4589 (ISSN-L)
OpenAlex
W2896040956
Cited by
68
References
57
Citations by year
2026: 1 · 2025: 4 · 2024: 3 · 2023: 9 · 2022: 13 · 2021: 18 · 2020: 7 · 2019: 12 · 2018: 1
FWCI
6.53
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Aging (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institute for Health Research Health Protection Research Unit
  • National Institute for Health and Care Research
  • King's College London
  • Public Health England
  • National Institute on Aging (U01AG060908, U34AG051425)
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
epigenetic aging, replicative senescence, telomerase, hTERT, epigenetic age, telomere synthesis, cell immortalization, lifespan extension, cellular aging
MeSH terms
Age Factors, Cells, Cultured, Fibroblasts, Humans, Male, Mutation, Time Factors, Signal Transduction, Cellular Senescence, Telomerase, DNA Methylation, Endothelial Cells, Epigenesis, Genetic, Cell Proliferation

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