Author: Kabacik S1, Horvath S2, Cohen H3, Raj K1
Affiliation: <sup>1</sup>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.
<sup>2</sup>Departments of Human Genetics and Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
<sup>3</sup>Elizabeth House Medical Practice, Warlingham, Surrey CR6 9LF, United Kingdom.
Conference/Journal: Aging (Albany NY).
Date published: 2018 Oct 17
Other:
Special Notes: doi: 10.18632/aging.101588. [Epub ahead of print] , Word Count: 210
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.
KEYWORDS: ageing; epigenetic ageing; epigenetic clock; hTERT; senescence
PMID: 30332397 DOI: 10.18632/aging.101588