Makpol Suzana, Durani Lina Wati, Chua Kien Hui, Mohd Yusof Yasmin Anum, Ngah Wan Zurinah Wan
Department of Biochemistry, Faculty of Medicine, National University of Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia.
J Biomed Biotechnol. 2011;2011:506171. doi: 10.1155/2011/506171. Epub 2011 Mar 30.
This study determined the molecular mechanisms of tocotrienol-rich fraction (TRF) in preventing cellular senescence of human diploid fibroblasts (HDFs). Primary culture of HDFs at various passages were incubated with 0.5 mg/mL TRF for 24 h. Telomere shortening with decreased telomerase activity was observed in senescent HDFs while the levels of damaged DNA and number of cells in G(0)/G(1) phase were increased and S phase cells were decreased. Incubation with TRF reversed the morphology of senescent HDFs to resemble that of young cells with decreased activity of SA-β-gal, damaged DNA, and cells in G(0)/G(1) phase while cells in the S phase were increased. Elongated telomere length and restoration of telomerase activity were observed in TRF-treated senescent HDFs. These findings confirmed the ability of tocotrienol-rich fraction in preventing HDFs cellular ageing by restoring telomere length and telomerase activity, reducing damaged DNA, and reversing cell cycle arrest associated with senescence.
本研究确定了富含生育三烯酚的组分(TRF)预防人二倍体成纤维细胞(HDFs)细胞衰老的分子机制。将不同传代的原代培养HDFs与0.5mg/mL的TRF孵育24小时。在衰老的HDFs中观察到端粒缩短且端粒酶活性降低,同时受损DNA水平和G(0)/G(1)期细胞数量增加,而S期细胞减少。用TRF孵育可使衰老HDFs的形态恢复为类似于年轻细胞,SA-β-半乳糖苷酶活性降低、受损DNA减少、G(0)/G(1)期细胞减少,而S期细胞增加。在经TRF处理的衰老HDFs中观察到端粒长度延长和端粒酶活性恢复。这些发现证实了富含生育三烯酚的组分通过恢复端粒长度和端粒酶活性、减少受损DNA以及逆转与衰老相关的细胞周期停滞来预防HDFs细胞衰老的能力。