期刊
CELLS
卷 11, 期 18, 页码 -出版社
MDPI
DOI: 10.3390/cells11182784
关键词
Hutchinson-Gilford progeria syndrome (HGPS); telomerase; telomere length; cell senescence; beta-galactosidase
类别
Establishing five immortalized HGP fibroblast cell lines using retroviral infection with the catalytic subunit of hTERT demonstrated enhanced proliferative lifespan and reduced senescence signs, with growth increase and phenotype improvement independent of telomere elongation. The initial telomeric stabilization after hTERT infection and relatively low amounts of hTERT mRNA were sufficient for phenotype improvement, suggesting implications for therapeutic strategies in HGP and other premature aging syndromes.
Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging syndrome caused by a dominant mutation in the LMNA gene. Previous research has shown that the ectopic expression of the catalytic subunit of telomerase (hTERT) can elongate the telomeres of the patients' fibroblasts. Here, we established five immortalized HGP fibroblast cell lines using retroviral infection with the catalytic subunit of hTERT. Immortalization enhanced the proliferative life span by at least 50 population doublings (PDs). The number of cells with typical senescence signs was reduced by 63 + 17%. Furthermore, the growth increase and phenotype improvement occurred with a lag phase of 50-100 days and was not dependent on the degree of telomere elongation. The initial telomeric stabilization after hTERT infection and relatively low amounts of hTERT mRNA were sufficient for the phenotype improvement but the retroviral infection procedure was associated with transient cell stress. Our data have implications for therapeutic strategies in HGP and other premature aging syndromes.
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