Synchronous deficits in cumulative muscle protein synthesis and ribosomal biogenesis underlie age-related anabolic resistance to exercise in humans.
Synchronous deficits in cumulative muscle protein synthesis and ribosomal biogenesis underlie age-related anabolic resistance to exercise in humans.
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DOI：
10.1113/jp272857
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发表时间：
2016-12-15
期刊：
影响因子：
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通讯作者：
Atherton PJ
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作者：
Brook MS;Wilkinson DJ;Mitchell WK;Lund JN;Phillips BE;Szewczyk NJ;Greenhaff PL;Smith K;Atherton PJ
阻力运动训练(RET)是防止骨骼肌群和力量随年龄增长而下降的最有效的策略之一。与年轻个体相比，RET的肥大反应随年龄增长而减弱。在对6周的RET的反应中，我们发现随着年龄的增长，迟钝的肥大反应受到长期肌肉蛋白质合成的慢性缺陷的支持。我们表明，这可能是合成激素的多因素缺陷以及迟钝的翻译效率和能力的结果。这些结果为了解与年龄相关的运动适应提供了很大的洞察力，并提供了一个平台，在此基础上制定更长期的适当营养和运动干预措施。衰老与抵抗运动训练(RET)的肥大反应受损有关。在这里，我们调查了老年人“合成代谢抵抗”的病因学。20名健康男性个体，10名年轻(23岁±1岁)和10名老年(69岁±13岁)，进行了6周的单侧RET(6次×8次，75%的1次重复(1-RM)，每周3次)。在基线的双侧股外侧肌(VL)肌肉活检后，受试者消耗150毫升D2O(70原子%；此后每周50毫升−-1)，在3周和6周时进一步采集双侧股外侧肌活检组织，通过气相色谱-裂解-同位素比质谱仪定量肌肉蛋白质合成(MPS)。RET后，1-RM在Y组(+35%±10.4%)和O组(+25%±0.03%；P<0.01)增加，而MVC在Y组(+21%±0.5%；P<0.01)增加，但O组(+6%±0.03%；无显著(NS))增加。与Y组相比，O组大鼠肌肉厚度明显增加(3周和6周时，Y组分别为+8±0.01%和+11±0.02%，P<0.01；O组分别为+2.6%±0.01%和+3.5%±0.02%)。而基础长期MPS在Y和O之间是相同的(∼为1.35%±0.1%/天−1)，而MPS仅在Y组增加(3周，Y：1.61%±0.1%/天−1；O：1.49%±0.1%/天−1)。与此一致的是，O表现为核糖体生物合成(核糖体比和c-myc诱导：Y：+4±2倍变化；O：+1.9倍±1倍变化)、翻译效率(S6K1磷酸化，Y：+10倍±2倍变化；O：+4倍±2倍变化)和合成激素环境(睾酮，Y：367±9.19；O：274±0.19 ng/dl−1(均P<；P均<0.05)。因此，合成代谢抵抗力是多因素的。阻力运动训练(RET)是防止骨骼肌群和力量随年龄增长而下降的最有效的策略之一。与年轻个体相比，RET的肥大反应随年龄增长而减弱。在对6周的RET的反应中，我们发现随着年龄的增长，迟钝的肥大反应受到长期肌肉蛋白质合成的慢性缺陷的支持。我们表明，这可能是合成激素的多因素缺陷以及迟钝的翻译效率和能力的结果。这些结果为了解与年龄相关的运动适应提供了很大的洞察力，并提供了一个平台，在此基础上制定更长期的适当营养和运动干预措施。
Resistance exercise training (RET) is one of the most effective strategies for preventing declines in skeletal muscle mass and strength with age. Hypertrophic responses to RET with age are diminished compared to younger individuals. In response to 6 weeks RET, we found blunted hypertrophic responses with age are underpinned by chronic deficits in long‐term muscle protein synthesis. We show this is likely to be the result of multifactorial deficits in anabolic hormones and blunted translational efficiency and capacity. These results provide great insight into age‐related exercise adaptations and provide a platform on which to devise appropriate nutritional and exercise interventions on a longer term basis. Ageing is associated with impaired hypertrophic responses to resistance exercise training (RET). Here we investigated the aetiology of ‘anabolic resistance’ in older humans. Twenty healthy male individuals, 10 younger (Y; 23 ± 1 years) and 10 older (O; 69 ± 3 years), performed 6 weeks unilateral RET (6 × 8 repetitions, 75% of one repetition maximum (1‐RM), 3 times per week). After baseline bilateral vastus lateralis (VL) muscle biopsies, subjects consumed 150 ml D2O (70 atom%; thereafter 50 ml week−1), further bilateral VL muscle biopsies were taken at 3 and 6 weeks to quantify muscle protein synthesis (MPS) via gas chromatography–pyrolysis–isotope ratio mass spectrometry. After RET, 1‐RM increased in Y (+35 ± 4%) and O (+25 ± 3%; P < 0.01), while MVC increased in Y (+21 ± 5%; P < 0.01) but not O (+6 ± 3%; not significant (NS)). In comparison to Y, O displayed blunted RET‐induced increases in muscle thickness (at 3 and 6 weeks, respectively, Y: +8 ± 1% and +11 ± 2%, P < 0.01; O: +2.6 ± 1% and +3.5 ± 2%, NS). While ‘basal’ longer term MPS was identical between Y and O (∼1.35 ± 0.1% day−1), MPS increased in response to RET only in Y (3 weeks, Y: 1.61 ± 0.1% day−1; O: 1.49 ± 0.1% day−1). Consistent with this, O exhibited inferior ribosomal biogenesis (RNA:DNA ratio and c‐MYC induction: Y: +4 ± 2 fold change; O: +1.9 ± 1 fold change), translational efficiency (S6K1 phosphorylation, Y: +10 ± 4 fold change; O: +4 ± 2 fold change) and anabolic hormone milieu (testosterone, Y: 367 ± 19; O: 274 ± 19 ng dl−1 (all P < 0.05). Anabolic resistance is thus multifactorial. Resistance exercise training (RET) is one of the most effective strategies for preventing declines in skeletal muscle mass and strength with age. Hypertrophic responses to RET with age are diminished compared to younger individuals. In response to 6 weeks RET, we found blunted hypertrophic responses with age are underpinned by chronic deficits in long‐term muscle protein synthesis. We show this is likely to be the result of multifactorial deficits in anabolic hormones and blunted translational efficiency and capacity. These results provide great insight into age‐related exercise adaptations and provide a platform on which to devise appropriate nutritional and exercise interventions on a longer term basis.