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

被引:53
作者
Kabacik, Sylwia [1 ]
Horvath, Steve [2 ,3 ]
Cohen, Howard [4 ]
Raj, Kenneth [1 ]
机构
[1] Publ Hlth England PHE Dicot, Ctr Radiat Chem & Environm Hazards CRCE, Radiat Effects Dept, Cellular Biol Grp, Chilton OX11 0RQ, Oxon, England
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biostat, Los Angeles, CA 90095 USA
[4] Elizabeth House Med Practice, Warlingham CR6 9LF, Surrey, England
来源
AGING-US | 2018年 / 10卷 / 10期
关键词
epigenetic ageing; hTERT; epigenetic clock; ageing; senescence; DNA METHYLATION AGE; CELLULAR SENESCENCE; CHRONOLOGICAL AGE; BIOLOGICAL AGE; CLOCK ANALYSIS; BLOOD; CELLS; CANCER; TETRAHYMENA; ENZYME;
D O I
10.18632/aging.101588
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:2800 / 2815
页数:16
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