Balagopal P, Schimke J C, Ades P, Adey D, Nair K S
Endocrinology Division, Mayo Clinic, 200 First St., Rochester, Minnesota 55905, USA.
Am J Physiol Endocrinol Metab. 2001 Feb;280(2):E203-8. doi: 10.1152/ajpendo.2001.280.2.E203.
Experimental evidence indicates that a lower synthesis rate of muscle contractile protein myosin heavy chain (MHC) occurs in age-related muscle wasting and weakness. To determine the molecular mechanism of this lower synthesis of MHC, we measured transcript levels of isoforms of MHC (MHCI, MHCIIa, and MHCIIx) in muscle biopsy samples of 7 young (20-27 yr), 12 middle-aged (47-60 yr), and 14 older (>65 yr) people. We further determined the effect of 3 mo of resistance exercise training (exercise) vs. nonintervention (control) on transcript levels of MHC isoforms on these subjects and the fractional synthesis rate (FSR) of MHC in 39 people aged 46-79 yr. MHCI mRNA levels did not significantly change with age, but MHCIIa decreased 38% (P < 0.05) from young to middle age and further decreased 50% (P < 0.05) from middle to old age. MHCIIx decreased 84% (P < 0.05) from young to middle age and 48% from middle to old age (P < 0.05). Exercise increased FSR of MHC by 47% (P < 0.01) and mixed muscle protein by 56% (P < 0.05). Exercise training results in an increase (85%) in transcript levels of MHCI and a decrease in the transcript levels of MHCIIa and MHCIIx. In conclusion, an age-related lowering of the transcript levels of MHCIIa and MHCIIx is not reversed by exercise, whereas exercise results in a higher synthesis rate of MHC in association with an increase in MHCI isoform transcript levels.
实验证据表明,在与年龄相关的肌肉萎缩和虚弱过程中,肌肉收缩蛋白肌球蛋白重链(MHC)的合成速率降低。为了确定MHC合成降低的分子机制,我们测量了7名年轻人(20 - 27岁)、12名中年人(47 - 60岁)和14名老年人(>65岁)肌肉活检样本中MHC亚型(MHCI、MHCIIa和MHCIIx)的转录水平。我们进一步确定了3个月的抗阻运动训练(运动组)与不干预(对照组)对这些受试者MHC亚型转录水平以及39名46 - 79岁人群中MHC的分数合成率(FSR)的影响。MHCI mRNA水平并未随年龄显著变化,但MHCIIa从青年到中年降低了38%(P < 0.05),从中年到老年进一步降低了50%(P < 0.05)。MHCIIx从青年到中年降低了84%(P < 0.05),从中年到老年降低了48%(P < 0.05)。运动使MHC的FSR提高了47%(P < 0.01),使混合肌肉蛋白提高了56%(P < 0.05)。运动训练导致MHCI转录水平增加(85%),而MHCIIa和MHCIIx转录水平降低。总之,与年龄相关的MHCIIa和MHCIIx转录水平降低不会因运动而逆转,而运动导致MHC合成速率提高,同时伴有MHCI亚型转录水平增加。