肌肉骨骼减少症发病机制及其运动防治效果

肌肉骨骼减少症（osteosarcopenia,OS）是一种多因素、多病因的退行性代谢综合征,其影响因素可能与衰老导致的机械、遗传、炎症因子、内分泌紊乱以及生活方式不规律相关。OS患者具有更高跌倒、骨折、活动障碍和死亡的风险,随着中国全球老龄化进程的加快,OS已经成为不容忽视的公共健康问题。近年来,国内外学者针对OS开展了大量的研究,但其发病机制仍不清楚。了解与OS相关的信号通路对进一步研究其发病机制和寻找治疗的新靶点具有重要意义。而运动作为现有效果强、持续性好的非药物治疗方式,能够增加老年人肌肉质量、提高骨密度、改善生活质量等,从而有效地预防和改善OS。本文主要就OS的流行病学、诊断标准、共同参与调节肌细胞与骨骼细胞代谢过程的相关信号通路（PI3K/Akt通路、Wnt/β-catenin通路、Notch通路、NF-κB通路）,以及不同运动方式对OS的干预效果等方面进行综述,以期为临床治疗OS提供理论依据,提高老年疾病的预防能力。     

Effects of diet on nutritional content of whole vertebrate prey

Proximate composition (moisture, lipid, protein, ash), vitamin A and vitamin E content, and six minerals (Cu, Fe, Zn, Mg, Mn, Ca) were measured in quail, rats, mice, and guinea pigs raised on at least two different diets per species. Feed composition varied substantially but erratically in lipid, vitamin A, vitamin E, and mineral content. All unsupplemented feeds had less vitamin E than NRC recommendations and most feeds contained less Mn than recommended. Most feeds deviated from the manufacturer's guaranteed analysis. There were significant effects of diet on body mass, moisture, lipid, ash, vitamin A, vitamin E, Ca, and Cu content for quail. There was a significant effect of diet on vitamin A content of mice; there were no other effects of diet on mammalian species. There was no correlation between diet composition and body composition for any species. Rats and mice differed significantly in vitamin A, Fe, and Cu content when raised on the same diet. We suggest that (1) it is difficult to assume or assess composition or adequacy of commercial diets without laboratory analysis, (2) supplementation of diets with whole foods can potentially reduce diet quality, (3) nutrient differences in quail are related to differences in growth, and such age-related differences may be more important in determining nutrient content than diet, (4) there were significant species differences in responsiveness to changes in diet, and (5) whole domesticated prey are a potentially inadequate source of vitamin E for raptors and of Mn and Cu for all carnivores. © 1996 Wiley-Liss, Inc.     

Assessment of nutritional status in rhesus monkeys: comparison of dual-energy X-ray absorptiometry and stable isotope dilution

Body composition estimates from dual-energy X-ray absorptiometry and stable isotope dilution ((2)H and (18)O) were compared in 61 rhesus monkeys (Macaca mulatta) from the ongoing long-term energy restriction study at the University of Wisconsin. Their average age was 18.9 +/- 2.5 y/o. Of the animals, 51% were in the energy restricted group and 38% were females. Although the correlation between methods was highly significant for fat mass (R(2) = 0.97, SEE = 0.25 kg or 7.5%, P < 0.0001) and fat-free mass (R(2) = 0.98, SEE = 0.29 kg or 3.6%, P < 0.0001), we observed that dual-energy X-ray absorptiometry underestimated fat mass by 0.67 +/- 0.26 kg (7.5%, P < 0.0001) and overestimated fat-free mass by 0.57 +/- 0.29 kg (20%, P < 0.0001) when compared with isotope dilution. Taken together with data from the literature, the present results emphasize the usefulness of dual-energy X-ray absorptiometry to derive body composition and thus nutritional status in monkeys, but demonstrate the importance of validation experiments for a given DXA model and software.     

Exercise and glycogen depletion: effects on ability to activate muscle phosphorylase

Phosphorylase activation reverses during prolonged contractile activity. Our first experiment was designed to determine whether this loss of ability to activate phosphorylase by stimulation of muscle contraction persists following exercise. Phosphorylase activation by stimulation of muscle contraction was markedly inhibited in rats 25 min after exhausting exercise. To evaluate the role of glycogen depletion, we accelerated glycogen utilization by nicotinic acid administration. A large difference in muscle glycogen depletion during exercise of the same duration did not influence the blunting of phosphorylase activation. Phosphorylase activation by stimulation of contraction was more severely inhibited following prolonged exercise than after a shorter bout of exercise under conditions that resulted in the same degree of glycogen depletion. A large difference in muscle glycogen repletion during 90 min of recovery was not associated with a significant difference in the ability of muscle stimulation to activate phosphorylase, which was still significantly blunted. Phosphorylase activation by epinephrine was also markedly inhibited in muscle 25 min after strenuous exercise but had recovered completely in glycogen-repleted muscle 90 min after exercise. These results provide evidence that an effect of exercise other than glycogen depletion is involved in causing the inhibition of phosphorylase activation; however, they do not rule out the possibility that glycogen depletion also plays a role in this process.     

下肢可调负重支具训练联合渐进性抗阻运动训练对股骨粗隆间骨折术后患者康复效果、髋关节功能和生活质量的影响

摘要 目的：探讨下肢可调负重支具训练联合渐进性抗阻运动训练在股骨粗隆间骨折术后患者中的应用效果。方法：按照随机数字表法将我院2020年3月~2021年6月间收治的93例股骨粗隆间骨折术后患者分为对照组（n=46,接受常规训练、渐进性抗阻运动训练）和研究组（n=47,接受常规训练、渐进性抗阻运动训练联合下肢可调负重支具训练）。观察并对比两组患者的临床指标、髋关节功能、疼痛情况、生活质量和并发症发生率。结果：与对照组相比,研究组的骨折愈合时间、住院天数、首次下床活动时间明显缩短（P<0.05）。干预1个月后、干预3个月后、干预6个月后,两组Harris髋关节功能评分依次升高,视觉疼痛模拟评分（VAS）依次下降（P<0.05）,干预1个月后、干预3个月后、干预6个月后,研究组Harris髋关节功能评分高于对照组,VAS评分低于对照组（P<0.05）。干预6个月后,两组简明健康调查量表（SF-36）各维度评分均升高,且研究组高于对照组（P<0.05）。两组并发症发生率组间对比,差异不显著（P>0.05）。结论：股骨粗隆间骨折术后患者采用下肢可调负重支具训练联合渐进性抗阻运动训练,可促进髋关节功能恢复,减轻疼痛症状,提高生活质量。     

Effect of oral theaflavin administration on body weight,fat, and muscle in healthy subjects: a randomized pilot study

Theaflavins are reddish-colored polyphenols in black tea. To test the efficacy of theaflavin administration on body fat and muscle, we performed a randomized, double-blind, placebo-controlled study and investigated the effect of theaflavins administration on the body composition using of healthy subjects. In this study, 30 male and female Japanese were enrolled and participants were randomly allocated to receive placebo, theaflavin (50 or 100 mg/day), or catechin (400 mg/ml) for 10 weeks. The effects were evaluated using body weight, body fat percentage, subcutaneous fat percentage, and skeletal muscle percentage. Theaflavin administration significantly improved body fat percentage, subcutaneous fat percentage, and skeletal muscle percentage when compared to with the placebo. In contrast, there was no significant difference in all measured outcomes between the catechin and the placebo groups. The results indicate that oral administration of theaflavin had a beneficial effect on body fat and muscle in healthy individuals.     

葛根异黄酮对去卵巢大鼠骨质疏松症的影响

通过对3月龄Wister大鼠,手术切除双侧卵巢后7天,每天灌胃TIP40mg/kg和10mg/kg,并设去卵巢组(OVX)、假手术组(Sham)和尼尔雌醇阳性对照组(OVX-E2),在给药3个月时,测定大鼠股骨骨矿密度(BMD)、骨钙及血清钙水平等,研究葛根异黄酮(TIP)对由雌激素缺乏引起的骨质疏松症的防治作用。结果TIP40mg/kg的BMD比去卵巢组显著提高了18.1%;使胫骨和血清钙含量显著增加;使去卵巢大鼠的脾脏重量系数和胸腺重量系数明显恢复;并可明显控制大鼠的体重。葛根异黄酮可能具有雌激素样活性,并有改善骨质疏松症的生物学活性。     

Whole body bone,fat and lean mass in children: Comparison of three ethnic groups

We measured whole body bone, fat and lean mass, by dual-energy x-ray absorptiometry, of third-grade children in a suburban public school district adjacent to Detroit. Of 1,340 eligible children, 773 participated. Using U.S. Census categories, parents identified their children as black/African-American (57%), white (38%), or one of several other categories (5%). Some of the participants also identified with a relatively large Middle Eastern subgroup (Chaldeans). Of the 773 participants, 734 are included in this report (71 Chaldeans, 226 whites, and 437 black/African-Americans; other categories are omitted). We describe body size, body composition, and physical activity levels in the three groups. The Chaldean and black children have significantly higher average whole body bone mineral content (BMC) than whites (P > 0.05), but are not different from each other. Lean mass and height are significantly greater for Chaldeans and blacks than for whites. The ratio of BMC to height was also significantly greater in Chaldeans and blacks compared with whites. Chaldeans have a significantly higher weight and fat mass than either the black or white children, and report significantly less physical activity than either the white or the black children. The higher bone mass among the Chaldean children may be partially explained by their greater body mass, but there is no readily apparent explanation for the observed ethnic differences in body size. We cannot exclude genetic or environmental factors not evaluated in this observational study. Our unexpected finding that Chaldean children, when analyzed as a separate group, are more similar in body composition to black/African-American than to white children contributes to a growing body of literature indicating that the uncritical use of “race” categories may obscure rather than facilitate the identification of population differences. Am J Phys Anthropol 103:157–162, 1997. © 1997 Wiley-Liss, Inc.     

The impact of aging on mitochondrial function and biogenesis pathways in skeletal muscle of sedentary high- and low-functioning elderly individuals

Age-related loss of muscle mass and strength (sarcopenia) leads to a decline in physical function and frailty in the elderly. Among the many proposed underlying causes of sarcopenia, mitochondrial dysfunction is inherent in a variety of aged tissues. The intent of this study was to examine the effect of aging on key groups of regulatory proteins involved in mitochondrial biogenesis and how this relates to physical performance in two groups of sedentary elderly participants, classified as high- and low-functioning based on the Short Physical Performance Battery test. Muscle mass was decreased by 38% and 30% in low-functioning elderly (LFE) participants when compared to young and high-functioning elderly participants, respectively, and positively correlated to physical performance. Mitochondrial respiration in permeabilized muscle fibers was reduced (41%) in the LFE group when compared to the young, and this was associated with a 30% decline in cytochrome c oxidase activity. Levels of key metabolic regulators, SIRT3 and PGC-1α, were significantly reduced (50%) in both groups of elderly participants when compared to young. Similarly, the fusion protein OPA1 was lower in muscle from elderly subjects; however, no changes were detected in Mfn2, Drp1 or Fis1 among the groups. In contrast, protein import machinery components Tom22 and cHsp70 were increased in the LFE group when compared to the young. This study suggests that aging in skeletal muscle is associated with impaired mitochondrial function and altered biogenesis pathways and that this may contribute to muscle atrophy and the decline in muscle performance observed in the elderly population.     

The effect of physiological stimuli on sarcopenia; impact of Notch and Wnt signaling on impaired aged skeletal muscle repair

The age-related loss of skeletal muscle mass and function that is associated with sarcopenia can result in ultimate consequences such as decreased quality of life. The causes of sarcopenia are multifactorial and include environmental and biological factors. The purpose of this review is to synthesize what the literature reveals in regards to the cellular regulation of sarcopenia, including impaired muscle regenerative capacity in the aged, and to discuss if physiological stimuli have the potential to slow the loss of myogenic potential that is associated with sarcopenia. In addition, this review article will discuss the effect of aging on Notch and Wnt signaling, and whether physiological stimuli have the ability to restore Notch and Wnt signaling resulting in rejuvenated aged muscle repair. The intention of this summary is to bring awareness to the benefits of consistent physiological stimulus (exercise) to combating sarcopenia as well as proclaiming the usefulness of contraction-induced injury models to studying the effects of local and systemic influences on aged myogenic capability.     

Maintenance of muscle mass and load‐induced growth in Muscle RING Finger 1 null mice with age

Age‐related loss of muscle mass occurs to varying degrees in all individuals and has a detrimental effect on morbidity and mortality. Muscle RING Finger 1 (MuRF1), a muscle‐specific E3 ubiquitin ligase, is believed to mediate muscle atrophy through the ubiquitin proteasome system (UPS). Deletion of MuRF1 (KO) in mice attenuates the loss of muscle mass following denervation, disuse, and glucocorticoid treatment; however, its role in age‐related muscle loss is unknown. In this study, skeletal muscle from male wild‐type (WT) and MuRF1 KO mice was studied up to the age of 24 months. Muscle mass and fiber cross‐sectional area decreased significantly with age in WT, but not in KO mice. In aged WT muscle, significant decreases in proteasome activities, especially 20S and 26S β5 (20–40% decrease), were measured and were associated with significant increases in the maladaptive endoplasmic reticulum (ER) stress marker, CHOP. Conversely, in aged MuRF1 KO mice, 20S or 26S β5 proteasome activity was maintained or decreased to a lesser extent than in WT mice, and no increase in CHOP expression was measured. Examination of the growth response of older (18 months) mice to functional overload revealed that old WT mice had significantly less growth relative to young mice (1.37‐ vs. 1.83‐fold), whereas old MuRF1 KO mice had a normal growth response (1.74‐ vs. 1.90‐fold). These data collectively suggest that with age, MuRF1 plays an important role in the control of skeletal muscle mass and growth capacity through the regulation of cellular stress.     

Effects of marine oligomeric polyphenols on body composition and physical ability of elderly individuals with sarcopenia: a pilot study

[Purpose]We aimed to identify the effects of marine oligomeric polyphenol (MOP) intake in elderly individuals with sarcopenia.[Methods]Older adults (aged 65 years or older) were recruited based on the diagnostic criterion for sarcopenia and were randomly assigned to the MOP intake group (n=10) or the placebo (PBO) intake group (n=10). To determine the effect of MOP intake received for four weeks, the pre- and post-intake body composition (weight, skeletal muscle mass, and bone density) and senior fitness tests were assessed.[Results]Our results showed there were significant differences in the skeletal muscle mass (p=0.039), bone density (p=0.020), fat-free mass index (p=0.026), and 2.4 m up and go test (p=0.001) between pretest and post-test. There was a significant difference between the pre-test and post-test and an interaction effect for the one-leg stand test (p=0.010 and p=0.049, respectively). However, there were no significant differences in body fat percentage, calf circumference, grip strength, or the chair rise test.[Conclusion]Some variables exhibited significant differences in the pre- and post-assessments, and there was an interaction effect for the one-leg stand. However, this was insufficient to prove the effectiveness of MOP intake in improving sarcopenia. Therefore, additional studies are essential to examine the effects of MOP intake and exercise intervention on the body composition and fitness of patients over a longer period.     

综述与专论：运动经外泌体防治肌少症的研究进展

肌少症（sarcopenia）是以骨骼肌质量和肌力进行性下降为特征的增龄性综合征,探究其发病机理对于肌少症的预防与治疗具有重要意义。研究表明,外泌体（exosomes）与肌少症关联密切,可能是一种有益的削弱/防治手段,但其机制尚未厘清。近期研究表明,外泌体富含运动因子/细胞因子,其不仅参与机体细胞与组织间的交互作用（cross talk）,亦介导了包括骨骼肌细胞增殖与分化在内的诸多病理生理过程。此外,运动可通过促进外泌体的释放并调节外泌体携带的miRNAs和/或蛋白质的表达,从而有效改善肌少症。本文就外泌体及其生物学特性以及外泌体与肌少症之间的关系进行归纳梳理,总结并分析运动对外泌体的影响及其可能机制,以期为肌少症的防治提供新的策略。     

振动训练对50～65岁老年人下肢骨骼肌激活特征和生理负荷的影响*

目的: 观察中老年人进行振动训练时下肢骨骼肌激活特征和生理负荷指标,探讨将振动训练应用于中老年人的可行性。方法: 选取28名50～65岁健康中老年人作为研究对象,分别在振动条件下(VT)和无振动条件下(NT)进行5次40 s静力半蹲练习,测试下肢主要肌群表面肌电和生理负荷指标。结果: ①VT受试者腓肠肌内侧(MG)、腓肠肌外侧(LG)、胫骨前肌(TA)、股直肌(RF)、股内侧肌(VM)、股外侧肌(VL)、股二头肌(BF)、半腱肌(ST)均方根振幅(RMS)显著高于NT(P＜0.01,P＜0.05),VL、BF、ST、MG、LG、TA平均功率频率(MPF)显著高于NT(P＜0.05);VM、VL、BF、MG、LG、TA平均功率斜率(MPF slope)显著高于NT(P＜0.05);②VT受试者心率和摄氧量显著高于NT(P＜0.05),主观疲劳等级(RPE)与NT比较无显著差异;③VT受试者尿素氮与NT无显著差异。结论: 50～65岁中老年人采用施加振动刺激的静力半蹲练习可以使机体募集更多的运动单位和更高比例的快肌纤维参与工作,在不增加主观疲劳感的基础上增加运动强度,同时未发现肌肉损伤。     

SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass

Increased expression of SIRT1 extends the lifespan of lower organisms and delays the onset of age‐related diseases in mammals. Here, we show that SRT2104, a synthetic small molecule activator of SIRT1, extends both mean and maximal lifespan of mice fed a standard diet. This is accompanied by improvements in health, including enhanced motor coordination, performance, bone mineral density, and insulin sensitivity associated with higher mitochondrial content and decreased inflammation. Short‐term SRT2104 treatment preserves bone and muscle mass in an experimental model of atrophy. These results demonstrate it is possible to design a small molecule that can slow aging and delay multiple age‐related diseases in mammals, supporting the therapeutic potential of SIRT1 activators in humans.     

Catch‐up and targeted growth following variable duration protein restriction: Effects on bone and body mass

Protein malnutrition leads to growth retardation that can be reversed through catch‐up growth, once normative nutrition is restored. Because growth is a dynamic process, catch‐up capacity is likely influenced by the maturity of the animal and/or the duration of the insult, in addition to the type of insult experienced. We compared length of malnutrition, sexual dimorphism, body mass, and skeletal growth. Eighty Rattus norvegicus were divided into 10 treatment groups (five diets; male and female) and followed for more than 1 year. At weaning, animals were placed on either a control or low‐protein isocaloric diet. Three experimental groups were switched to the control diet at 40, 60, or 90 days. Beginning with 21 days of age, animals were weighed daily and radiographed throughout the study. To determine the presence of catch‐up growth, growth rates (GRs) were calculated (linear regression) for 20‐day time spans before and after diet changes and compared among treatment groups. Targeted growth was measured as final size or as the coefficient of variation with age. These results show that 1) protein‐restricted animals experience catch‐up growth with dietary rehabilitation; 2) for females, catch‐up GRs are proportional to GRs in control animals at the same age as the timing of dietary rehabilitation but not for males; and 3) targeted growth was observed in some, but not all, aspects of anatomy. The length of the tibia and humerus was indistinguishable from controls, regardless of length of malnutrition or gender, whereas the ulna and male body mass exceeded control sizes. Although most measures decreased in variation with ontogeny, the tibia failed to do so. These results support a complex biological regulation of catch‐up and targeted growth. The implications for selection are that flexible and responsive developmental trajectories may have an advantage over those programed into a single size. J. Morphol., 2011. © 2011 Wiley‐Liss, Inc.     

The effects of feeding regime on proximate body composition and patterns of energy deposition in juvenile Arctic charr, Salvelinus alpinus

Juvenile Arctic charr, Salvelinus alpinus , subjected to either food deprivation or restricted feeding showed reductions in relative sizes of both liver and viscera. With food deprivation, percentage lipid decreased and percentage water increased in the eviscerated carcass, which is in agreement with findings for several other fish species. Following transfer from a restricted to a satiation feeding regime, the relative sizes of both liver and viscera increased to levels exceeding those of fish fed continuously to satiation. At the end of the experiment the percentage liver lipid content of restricted-satiation fed fish was higher than in fish fed to satiation. These differences in energy deposition patterns were, however, not sufficiently large to produce marked differences at the whole animal level, since whole body lipid energy: protein energy ratios and energy utilization efficiencies were similar for restricted-satiation and satiation fed fish.