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

Sylwia Kabacik*, Steve Horvath, Howard Cohen, Kenneth Raj

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

The paramount role of senescent cells in ageing has prompted suggestions that re-expression of telomerase may prevent ageing; a proposition that is predicated on the assumption that senescent cells are the sole cause of ageing. Recently, several DNA methylation-based age estimators (epigenetic clocks) have been developed and they revealed that increased epigenetic age is associated with a host of age-related conditions, and is predictive of lifespan. Employing these clocks to measure epigenetic age in vitro, 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.

Original languageEnglish
Pages (from-to)2800-2815
Number of pages16
JournalAging
Volume10
Issue number10
DOIs
Publication statusPublished - 1 Oct 2018

Bibliographical note

Funding Information:
We would like to acknowledge the support from Simon Bouffler and all members of the Raj lab. The experimental research was funded by the National Institute for Health Research (NIHR) through Health Protection Research Unit (Health Impact of Environmental Hazards with King's College London) in partnership with Public Health England (PHE). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health or Public Health England.

Publisher Copyright:
© Kabacik et al.

Keywords

  • Ageing
  • Epigenetic ageing
  • Epigenetic clock
  • HTERT
  • Senescence

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