Translational Research Institute for Metabolism and Diabetes, Florida Hospital, 301 East Princeton Street, Orlando, FL, 32804, USA.
Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, 6400 Sanger Rd, Orlando, FL, 32827, USA.
J Cachexia Sarcopenia Muscle. 2018 Apr;9(2):279-294. doi: 10.1002/jcsm.12272. Epub 2018 Jan 24.
The concept of mitochondrial dysfunction in ageing muscle is highly controversial. In addition, emerging evidence suggests that reduced muscle oxidative capacity and efficiency underlie the aetiology of mobility loss in older adults. Here, we hypothesized that studying well-phenotyped older cohorts across a wide range of physical activity would unveil a range of mitochondrial function in skeletal muscle and in turn allow us to more clearly examine the impact of age per se on mitochondrial energetics. This also enabled us to more clearly define the relationships between mitochondrial energetics and muscle lipid content with clinically relevant assessments of muscle and physical function.
Thirty-nine volunteers were recruited to the following study groups: young active (YA, n = 2 women/8 men, age = 31.2 ± 5.4 years), older active (OA, n = 2 women/8 men, age = 67.5 ± 2.7 years), and older sedentary (OS, n = 8 women/11 men, age = 70.7 ± 4.7 years). Participants completed a graded exercise test to determine fitness (VO peak), a submaximal exercise test to determine exercise efficiency, and daily physical activity was recorded using a tri-axial armband accelerometer. Mitochondrial energetics were determined by (i) P magnetic resonance spectroscopy and (ii) respirometry of fibre bundles from vastus lateralis biopsies. Quadriceps function was assessed by isokinetic dynamometry and physical function by the short physical performance battery and stair climb test.
Daily physical activity energy expenditure was significantly lower in OS, compared with YA and OA groups. Despite fitness being higher in YA compared with OA and OS, mitochondrial respiration, maximum mitochondrial capacity, Maximal ATP production/Oxygen consumption (P/O) ratio, and exercise efficiency were similar in YA and OA groups and were significantly lower in OS. P/O ratio was correlated with exercise efficiency. Time to complete the stair climb and repeated chair stand tests were significantly greater for OS. Interestingly, maximum mitochondrial capacity was related to muscle contractile performance and physical function.
Older adults who maintain a high amount of physical activity have better mitochondrial capacity, similar to highly active younger adults, and this is related to their better muscle quality, exercise efficiency, and physical performance. This suggests that mitochondria could be an important therapeutic target for sedentary ageing associated conditions including sarcopenia, dynapenia, and loss of physical function.
线粒体功能障碍在衰老肌肉中的概念存在很大争议。此外,新出现的证据表明,肌肉氧化能力和效率的降低是老年人活动能力丧失的病因。在这里,我们假设通过研究广泛的体力活动范围内的表现良好的老年队列,将揭示骨骼肌中一系列线粒体功能,并使我们能够更清楚地检查年龄本身对线粒体能量代谢的影响。这也使我们能够更清楚地定义线粒体能量代谢与肌肉脂质含量之间的关系,并与肌肉和身体功能的临床相关评估相关联。
招募了 39 名志愿者参加以下研究组:年轻活跃组(YA,n=2 名女性/8 名男性,年龄=31.2±5.4 岁)、年老活跃组(OA,n=2 名女性/8 名男性,年龄=67.5±2.7 岁)和年老久坐组(OS,n=8 名女性/11 名男性,年龄=70.7±4.7 岁)。参与者完成了分级运动测试以确定体能(VOpeak)、亚最大运动测试以确定运动效率,并且使用三轴手臂加速度计记录日常体力活动。通过(i)P 磁共振波谱和(ii)来自股外侧肌活检的纤维束呼吸测定法来确定线粒体能量代谢。通过等速动力学测定法评估股四头肌功能,通过简短的身体表现电池和楼梯爬升测试评估身体功能。
与 YA 和 OA 组相比,OS 组的日常体力活动能量消耗明显较低。尽管 YA 组的体能高于 OA 和 OS 组,但 YA 和 OA 组的线粒体呼吸、最大线粒体容量、最大 ATP 产生/耗氧量(P/O)比值和运动效率相似,OS 组明显更低。P/O 比值与运动效率相关。OS 组完成楼梯爬升和重复椅子站立测试的时间明显更长。有趣的是,最大线粒体容量与肌肉收缩性能和身体功能相关。
保持大量体力活动的老年人具有更好的线粒体容量,与非常活跃的年轻人相似,这与他们更好的肌肉质量、运动效率和身体功能有关。这表明,线粒体可能是与久坐相关的衰老相关疾病(包括肌肉减少症、力量减弱和身体功能丧失)的重要治疗靶点。