Epigenetic ageing is distinct from senescence-mediated ageing and is not prevented by telomerase expression.
Epigenetic ageing is distinct from senescence-mediated ageing and is not prevented by telomerase expression.
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DOI：
10.18632/aging.101588
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发表时间：
2018-10-17
期刊：
影响因子：
--
通讯作者：
Raj K
中科院分区：
文献类型：
--
作者：
Kabacik S;Horvath S;Cohen H;Raj K
衰老细胞在衰老中的重要作用促使人们提出，端粒酶的重新表达可能会阻止衰老；这一假设是基于衰老细胞是衰老的唯一原因的假设。最近，一些基于DNA甲基化的年龄估计(表观遗传时钟)已经被开发出来，他们揭示了表观遗传年龄的增加与一系列年龄相关的疾病相关，并预测了寿命。利用这些时钟在体外测量表观遗传年龄，我们询问了表观遗传老化与端粒酶活性之间的关系。尽管hTERT没有引起表观遗传衰老速度的任何明显变化，但绕过衰老的hTERT表达细胞继续表观遗传衰老。HTERT突变体的使用表明，这些细胞继续延长表观遗传年龄既不需要端粒合成，也不需要永生化。相反，它们寿命的延长足以支持细胞继续表观遗传老化。在来自众多捐赠者和细胞类型的细胞中观察到的这些特征，揭示了表观遗传衰老与复制性衰老不同。因此，虽然重新激活hTERT可能通过避免复制衰老来延缓衰老的物理表现，但它对尽管端粒酶活性仍在继续的表观遗传衰老几乎没有影响。
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.
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影响因子：
3.7
作者：
Bocklandt S;Lin W;Sehl ME;Sánchez FJ;Sinsheimer JS;Horvath S;Vilain E
通讯作者：
Vilain E
DOI：
10.1093/infdis/jiv277
发表时间：
2015-11-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Horvath S;Levine AJ
通讯作者：
Levine AJ
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
5.7
作者：
Breitling LP;Saum KU;Perna L;Schöttker B;Holleczek B;Brenner H
通讯作者：
Brenner H
影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS