Epigenetic ageing is distinct from senescence-mediated ageing and is not prevented by telomerase expression
Open accessAbstract
, 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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Increase of DNA methylation age is not prevented by immortalization.
“several studies by the Steven Horvath and Ken Raj group show that the increase of DNAm age is not prevented by immortalization (Kabacik et al., 2022; Kabacik et al., 2018; Lu et al., 2018)”
From Gene Therapy-Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice (2024) · cites this paper as Kabacik et al., 2018
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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
- Publisher
- Impact Journals, LLC
- Published
- 2018-10-17
- Volume
- 10
- Issue
- 10
- Pages
- 2800-2815
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC6224244
- 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
- green
- europepmc.org
- 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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