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Epigenetic ageing is distinct from senescence-mediated ageing and is not prevented by telomerase expression
- Source :
- Aging (Albany NY)
- Publication Year :
- 2018
- Publisher :
- Impact Journals, LLC, 2018.
-
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.
- Subjects :
- Male
0301 basic medicine
Senescence
Aging
Cell type
Telomerase
Time Factors
senescence
epigenetic ageing
Biology
Epigenesis, Genetic
03 medical and health sciences
0302 clinical medicine
Humans
Telomerase reverse transcriptase
Epigenetics
Cells, Cultured
Cellular Senescence
Cell Proliferation
Age Factors
Endothelial Cells
Cell Biology
DNA Methylation
Fibroblasts
Cell biology
Telomere
030104 developmental biology
ageing
Ageing
030220 oncology & carcinogenesis
Mutation
DNA methylation
hTERT
epigenetic clock
Signal Transduction
Research Paper
Subjects
Details
- ISSN :
- 19454589
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Aging
- Accession number :
- edsair.doi.dedup.....90f81b4c196dc1ded067707bea6eba8d