Research Paper Volume 10, Issue 10 pp 2800—2815

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

Sylwia Kabacik 1, , Steve Horvath 2, , Howard Cohen 3, , Kenneth Raj 1, ,

  • 1 Cellular Biology Group, Radiation Effects Department, Centre for Radiation, Chemicals and Environmental Hazards (CRCE) Public Health England (PHE) Dicot, Chilton OX11 0RQ, Oxfordshire, United Kingdom
  • 2 Departments of Human Genetics and Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
  • 3 Elizabeth House Medical Practice, Warlingham, Surrey CR6 9LF, United Kingdom

received: August 6, 2018 ; accepted: October 4, 2018 ; published: October 17, 2018 ;

https://doi.org/10.18632/aging.101588
How to Cite

Copyright: Kabacik et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Abbreviations

CpG: CpG island; hTERT: the catalytic sub-unit of telomerase; SASP: senescence-associated secretory phenotype.