title: The Tocotrienol-Rich Fraction Is Superior to Tocopherol in Promoting Myogenic Differentiation in the Prevention of Replicative Senescence of Myoblasts.
abstract: Aging results in a loss of muscle mass and strength. Myoblasts play an important role in maintaining muscle mass through regenerative processes, which are impaired during aging. Vitamin E potentially ameliorates age-related phenotypes. Hence, this study aimed to determine the effects of the tocotrienol-rich fraction (TRF) and α-tocopherol (ATF) in protecting myoblasts from replicative senescence and promoting myogenic differentiation. Primary human myoblasts were cultured into young and senescent stages and were then treated with TRF or ATF for 24 h, followed by an analysis of cell proliferation, senescence biomarkers, cellular morphology and differentiation. Our data showed that replicative senescence impaired the normal regenerative processes of myoblasts, resulting in changes in cellular morphology, cell proliferation, senescence-associated β-galactosidase (SA-β-gal) expression, myogenic differentiation and myogenic regulatory factors (MRFs) expression. Treatment with both TRF and ATF was beneficial to senescent myoblasts in reclaiming the morphology of young cells, improved cell viability and decreased SA-β-gal expression. However, only TRF treatment increased BrdU incorporation in senescent myoblasts, as well as promoted myogenic differentiation through the modulation of MRFs at the mRNA and protein levels. MYOD1 and MYOG gene expression and myogenin protein expression were modulated in the early phases of myogenic differentiation. In conclusion, the tocotrienol-rich fraction is superior to α-tocopherol in ameliorating replicative senescence-related aberration and promoting differentiation via modulation of MRFs expression, indicating vitamin E potential in modulating replicative senescence of myoblasts.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Level 17, Preclinical Building, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.
authors.forename: Shy Cian
authors.initials: SC
authors.lastname: Khor
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Level 17, Preclinical Building, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.
authors.forename: Azraul Mumtazah
authors.initials: AM
authors.lastname: Razak
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Level 17, Preclinical Building, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.
authors.forename: Wan Zurinah
authors.initials: WZ
authors.lastname: Wan Ngah
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Level 17, Preclinical Building, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.
authors.forename: Yasmin Anum
authors.initials: YA
authors.lastname: Mohd Yusof
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Level 17, Preclinical Building, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.
authors.forename: Norwahidah
authors.initials: N
authors.lastname: Abdul Karim
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Level 17, Preclinical Building, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.
authors.forename: Suzana
authors.initials: S
authors.lastname: Makpol
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival; D016922:Cellular Senescence / Q000187:drug effects* / Q000235:genetics; D003893:Desmin / Q000378:metabolism; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008297:Male; D024510:Muscle Development / Q000187:drug effects*; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D024505:Tocopherols / Q000494:pharmacology*; D024508:Tocotrienols / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D015415:Biomarkers; D003893:Desmin; D005609:Free Radicals; D018006:Myogenic Regulatory Factors; D012333:RNA, Messenger; D024508:Tocotrienols; D014810:Vitamin E; D001616:beta-Galactosidase; D001973:Bromodeoxyuridine; D024505:Tocopherols