Chinese Journal of Tissue Engineering Research ›› 2013, Vol. 17 ›› Issue (24): 4545-4552.doi: 10.3969/j.issn.2095-4344.2013.24.025
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Wen Cai-xiong
Received:
2013-03-13
Revised:
2013-04-04
Online:
2013-06-11
Published:
2013-06-11
About author:
Wen Cai-xiong, Associate professor, Department of Basis, Guangdong Teachers College of Foreign Language and Arts, Guangzhou 510507, Guangdong Province, China
wxw2002@yahoo.cn
CLC Number:
Wen Cai-xiong. Resistance training and protein supplement: Improvement of elderly muscle protein metabolism[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(24): 4545-4552.
2.1 老年人肌肉蛋白质代谢与肌肉丢失 2.1.1 老年人肌肉丢失 肌肉是人体最先开始衰老的器官,一般人从40岁开始,肌肉质量和肌纤维数量便开始随增龄出现减少,这被称为肌肉丢失[2]。一般人在缺乏运动或生活方式从运动型向久坐型急速转变的时候,肌肉通常会出现一定程度的萎缩,同时伴有肌肉功能的衰退,但对年轻人来讲,这种衰退是可逆的,经过一定时间的运动锻炼之后,肌肉质量和功能都能够很快恢复到衰退之前的水平,因此这种变化与衰老无关。而由于衰老而导致的肌肉功能的衰退伴随着肌肉质量的减少和肌纤维数量的减少,这在一定程度上是不可逆的。研究表明,正常人肌肉丢失每年的进展率为0.6%,但经常从事运动锻炼或者从事体力工作的人,这个进展速度会减小,这说明,一方面肌肉丢失与肌肉功能衰退存在明显的个体差异[3];另一方面,合理的运动可以延缓肌肉功能衰退的进程。运动医学领域的研究则发现,一个人的肌肉储备(年轻时的肌肉量)越好,肌肉丢失开始的年龄越晚,每年肌肉丢失的进展率也越小[4]。 肌肉丢失的最直接原因就是老年人肌肉蛋白质代谢出现了问题。正常情况下,肌肉蛋白质合成和分解的速率是基本平衡的,当蛋白分解大于蛋白合成时,肌肉质量就会减小,甚至肌纤维坏死而致总体数量减少。除了衰老过程中某些复杂的细胞机制之外,老年人饮食的改变、运动活动的减少也是导致老年人肌肉蛋白质代谢失衡的重要原因。西方人日常生活中蛋白摄入量较中国人多,因为他们几乎将肉类食品当作主食,尽管如此,美国的一项调查表明,75岁以上的老年男性有70.2%以上,女性有76.4%以上的人存在蛋白摄入不足的问题[5]。一般而言,老年人膳食总量减少,消化吸收能力减弱,膳食结构中蛋白总量不足,加之老年人活动减少,这些足以造成老年人肌肉蛋白代谢的负平衡。关于老年人膳食结构的调查,很多研究都出自西方国家[6],中国与其他国家的对比研究还未见到。 2.1.2 老年人肌肉蛋白质代谢 老年肌肉蛋白合成的减少可能与饮食的改变有关,但老年人肌肉蛋白分解增加的机制则不十分清楚。一般认为,蛋白质消耗并未改变,而在蛋白合成能力降低的情况下,蛋白分解量相对而言就增加了[7]。也有研究认为,老年人肌肉蛋白合成减少和蛋白分解增加同时存在,这并不是相对而言蛋白分解增加了[8]。有研究对一组65岁的老年人和一组30岁的年轻人进行了肌肉蛋白质测试并进行了比较,结果发现,老年人局部肌肉蛋白合成减少了20%-30%,而蛋白水解标志物Surrogate却增加了50%[9]。这就说明,老年人肌肉蛋白质分解的绝对量较年轻人多,加之蛋白合成量减少,因而老年人肌肉蛋白负平衡的进展是相当明显的,这直接导致了老年人的肌肉丢失。事实上,老年人肌肉蛋白质代谢的负平衡状态的原因有许多,包括运动减少、体内某些激素的变化、膳食结果的改变等等,这些原因的叠加使得老年人肌肉蛋白质代谢负平衡的情况变得十分复杂。 有研究对经常从事运动或从事体力劳动的老年被试和同龄非运动、非体力劳动的被试进行调查比 较[10-11],结果显示,运动和体力劳动组的老年人肌肉量比非运动、非体力劳动者多,差异具有显著性意义。这说明,肌肉废用是引起老年人肌肉蛋白质代谢负平衡的主要原因。而有一项对久坐生活方式的老年人群的调查发现,50-80岁的人群中,肌纤维由于废用而减少的数量在0.5%-1.5%/年[12]。 动物实验研究发现,老龄大鼠肌肉利用氨基酸合成蛋白质的能力明显低于年轻大鼠,在同样喂食和运动条件下,年轻大鼠肌肉蛋白质合成量明显高于老龄组[13]。而一项针对老年人群调查的研究显示,在饮食和运动条件相同的老年人和年轻人中,老年人肌肉蛋白质合成量明显低于年轻人[14]。因此,衰老导致肌肉利用氨基酸合成蛋白能力的降低已是不争的事实。那么针对为什么会出现这样的情况,近年来学者们提出了一个新的概念:“合成代谢抵抗”(Anabolic Resistance)[15]。研究发现,在空腹状态下,老年人与年轻人肌肉蛋白合成率没有明显差别,当给予蛋白补充后,老年人肌细胞对于这种干预刺激的反应却明显低于年轻人,这就是合成代谢抵抗。进一步的研究认为,可能有两个因素与合成代谢抵抗有关,其一就是老年人运动活动的减少,肌细胞新陈代谢减慢;其二是老年人肌肉处理炎症能力的降低。在肌肉活动超出平常习惯状态时、轻微损伤时、甚至在自然衰老的过程中,肌肉都可能经历急性或者慢性炎症反应,这些炎性反应就会使得肌肉对蛋白质合成代谢的敏感性降低。关于炎性反应导致合成代谢抵抗的假设首先在动物实验中得到证实,研究发现,大鼠低水平的炎性反应损害了肌肉蛋白合成对喂食的反应[16]。但是,也有研究不同意合成代谢抵抗与炎性反应有关。Burd等[17]进行了大量的研究之后提出,老年人在肌肉炎性反应的情况下,令他们从事小负荷的抗阻训练,结果发现他们的合成代谢抵抗便会消失,因此,合成代谢抵抗的真正原因还是运动缺乏。也有学者提出,合成代谢抵抗仅仅是一种现象而已[18],其中并没有特殊的生理或者病理机制,或者说其真正的机制还远没有搞清楚。不管合成代谢是现象也好,还是某种机制作用下的结果,合成代谢抵抗或者说老年人肌肉对蛋白合成代谢的敏感性差是客观存在的,因此针对如何逆转这种“抵抗”的研究才是真正的研究焦点所在。许多研究都证明,老年人肌肉合成代谢对蛋白摄入敏感性降低是由于老年人内脏吸收了较年轻人更多的氨基酸所致[19-21]。口服氨基酸之后,老年人内脏吸收氨基酸较多,而肌肉得到的就较少。另有研究采用氨基酸注射的方法来绕过内脏吸收,结果发现老年人肌肉蛋白合成仍然显著低于年轻人的水平[22]。由此可见,老年人肌肉合成代谢的机制可能比较复杂。 2.1.3 影响老年肌肉合成代谢的机制研究 研究发现,肌肉合成代谢抵抗的一个重要原因在于,衰老肌细胞中的肿瘤细胞杀伤因子会通过钝化蛋白磷酸化在哺乳动物雷帕酶素靶蛋白(Mtor)的细胞内信号转导通路来损害肌肉蛋白合成[23]。研究者通过蛋白免疫印迹实验比较了老年人和青年人肌细胞中的Mtor,发现老年人肌细胞中Mtor的表达量显著低于年轻人。相关的动物实验则发现[24],肿瘤细胞杀伤因子这个最重要的诱导因素在肌肉蛋白合成代谢变化中起着重要作用,大鼠肌细胞中肿瘤细胞杀伤因子表达量与肌肉蛋白合成代谢率呈明显的正相关,与此同时,与雷帕酶素靶蛋白(mTOR)通路相关的信号蛋白被证明对氨基酸十分敏感。 近年来关于MG29蛋白的研究报道越来越多,MG29是肌细胞肌质网膜上的一种膜蛋白,它对肌细胞神经信号传导方面起着关键作用,是一种重要的功能蛋白。有研究将肌细胞组织学和蛋白免疫印迹实验结果对照[25],发现,MG29蛋白的表达量与肌纤维类型变化及运动单位重组存在某种联系,即MG29蛋白表达量的降低与Ⅱ型肌纤维的减少存在正相关。众多的研究已经证明,在衰老和疾病状态下,肌细胞MG29蛋白的基因表达出现明显下降,并且它与肌肉丢失存在密切关系[26-28]。而在干预性实验研究中发现,适宜的运动[29]、或蛋白补充以及运动结合蛋白补充都可以有效提高老龄大鼠肌细胞MG29蛋白的基因表达[30-31],并同时使得大鼠肌纤维横断面积增粗。这些研究说明,衰老过程中的肌肉蛋白质代谢不仅涉及肌肉的结构蛋白,同时也涉及到某些重要的功能蛋白。运动与营养干预可能对肌细胞蛋白质合成代谢,甚至对肌细胞中的某些功能蛋白产生有效的影响。 2.2 蛋白补充对老年肌肉蛋白质代谢的影响 肌肉蛋白合成代谢会受到蛋白质摄入的影响,具体地说,摄入的蛋白质可以通过影响血液晶氨酸的浓度和时间来影响肌肉蛋白合成,这种影响效果取决于摄入蛋白质的质量和时间。对年轻人来说,抗阻训练后补充5-10 g鸡蛋就可以有效地影响到他们肌肉蛋白合 成[32]。更多的研究发现,通常的蛋白补充剂的重要成分为乳清蛋白、酪蛋白和大豆蛋白,而乳清蛋白比酪蛋白和大豆蛋白更能促进肌肉蛋白合成代谢的反 应[33-35]。乳清蛋白在促进肌肉蛋白质代谢方面的作用远比大豆蛋白强,原因在于乳清蛋白在体内更容易被吸收,而且在以上3种蛋白中,乳清蛋白中的亮氨酸含量最高。此外,支链氨基酸——亮氨酸可能在调解肌肉蛋白合成中通过激活mTOR通道而实现调节肌肉蛋白质代谢的作用[36]。 Welle等 [37]比较不同蛋白比例的食物补充对年轻被试肌肉蛋白质代谢的影响,他们分别给被试补充低蛋白(占总能量的7%)、中等蛋白(14%)和高蛋白(28%)食物,结果发现它们对刺激肌肉蛋白合成的效果没有什么差异。另有学者则是给年轻被试饮用晶氨酸补剂,结果发现10 g晶氨酸就足以刺激肌纤维蛋白合成达到高水平,对老年人则需要20 g才能达到接近年轻人的效果[38]。营养学的研究表明,膳食中摄入过多的晶氨酸很难被肌肉吸收。因此有学者提出,蛋白质补充应当设定一个阈限,因为过多的补充会给机体增加负担[39]。 亮氨酸之所以引起研究者的注意是因为,有研究发现亮氨酸摄入或静脉注射都引起了mTOR 通路上的一个重要蛋白的磷酸化过程加剧。年轻人对于摄入亮氨酸的反应十分敏感,有研究专门针对亮氨酸补充效果进行了研究[40],结果发现年轻人肌肉蛋白质代谢对亮氨酸刺激的反应十分敏感,在饮食中增加1 g亮氨酸就可以促使其肌肉蛋白质合成水平显著高于平常。相比而言,老年人肌肉蛋白质代谢对于亮氨酸补充的敏感性就差了很多。 除了亮氨酸以外,酪氨酸也是有效促进肌肉蛋白质合成的氨基酸,有学者对这两种氨基酸的补充效果进行了比较[41],结果表明,较高的亮氨酸循环浓度(血液)比较高的酪氨酸浓度更能有效地促进肌肉蛋白合成。目前营养品市场流行的乳清蛋白就是因为它富含亮氨酸而受到消费者青睐,老年人蛋白质补充的实验研究也证明,乳清蛋白是较好的蛋白补剂。有研究报道,长期补充亮氨酸(每天7.5 g)使老年人肌肉力量和肌肉质量都有明显改善[42]。 有研究给老年被试补充8周多不饱和脂肪酸(Omega-3),结果被试肌细胞mTOR的信号转导得到了加强,肌肉合成代谢的蛋白磷酸化过程也得到增强[43]。但研究者们一致认为,Omega-3的抗炎症反应的功能是主要原因,因为老年人随年龄增长,肌肉炎症反应在不断增强,而这最终会影响肌肉蛋白质代谢。 2.3 抗阻训练结合蛋白补充对老年人肌肉蛋白质代谢的影响 老年人肌肉蛋白质代谢的负平衡导致了肌肉丢失,而这种负平衡部分是由于老年人膳食结构的改变引起的,因此有研究尝试给老年人增加蛋白摄入来改善他们蛋白摄入不足的问题。结果发现,补充蛋白的确可以明显增加老年人肌肉蛋白合成代谢水平,但这种增加是暂时的,在停止蛋白补充之后的短时间内,老年人肌肉蛋白合成代谢水平很快便恢复到原来的水平[44]。年轻人在正常饮食情况下,肌肉蛋白合成代谢水平会保持在一个正常状态下,而老年人则需要额外补充蛋白质饮食。这引发了老年人对蛋白质营养素的消化吸收能力降低的假设。 乳清蛋白被许多研究都证明是提高肌肉蛋白合成水平的有效食用蛋白补剂[45-47],在健身俱乐部和许多康复中心,乳清蛋白都是健身、健美锻炼者的首选营养补剂。研究发现,给从事适宜抗阻训练的老年人被试以乳清蛋白(每天10 g),经过12周之后,老年人肌肉蛋白合成水平明显得到提高[48]。另有研究报道,给老年人长达8个月的富含亮氨酸的乳清蛋白供食结合锻炼,并与单纯从事同样符合锻炼的老年人进行对照,发现乳清蛋白组被试肌肉质量和力量的增强都明显高于单纯锻炼组老年人[49]。研究者对结果的解释是,蛋白补充与抗阻训练结合可以更有效地刺激肌肉蛋白合成的效率,蛋白平衡的“摆动”(蛋白合成-蛋白消耗-蛋白再合成)有利于蛋白沉积,从而使肌肉肥大。 亮氨酸是一种被证明能有效刺激肌肉蛋白合成的营养补剂[50]。但是当给被试口服富含亮氨酸的蛋白补剂时,只有当补量达到一定水平时才能真正引起肌肉蛋白代谢增强的反应,这个补充的最小有效剂量被称为“亮氨酸阈”。研究发现,老年人亮氨酸阈普遍比年轻人高,说明老年人肌肉对蛋白摄入刺激的反应能力较年轻人差[51]。在很多研究中还发现,老年人在肌肉抗阻训练结合蛋白补充的实验中肌肉蛋白合成代谢的反应同样滞后于年轻人[52-53]。而Drummond等[54]发现,老年被试在抗阻训练之后,蛋白合成水平的提高比年轻人迟钝3-6 h,而在6 h之后老年人肌肉锻炼后合成代谢的信号反应可以缓慢提高到年轻人的水平。 近年来运动医学领域研究发现[55],采用体外限制工作肌群血流供应的情况下进行低强度(25%-50% 1RM)抗阻训练能够显著提高训练的效果。而关于此现象的机制研究证明[56],这种训练方法能够有效地促进mTOR信号转导的磷酸化过程。在针对老年被试的训练实验中也同样得到阳性的结果[57],研究表明,平均年龄65.2岁的一组被试从事低强度抗阻训练+体外血流限制(用橡皮绷带裹压上臂),每周训练2次,共进行18周的训练,结果被试肌肉合成代谢较安静时增加了57%。 研究发现,抗阻训练结合蛋白质补充可以有效地增强年轻人和老年人肌肉蛋白合成,而在训练前 1 h补充同样剂量的蛋白补剂时(4.5 g晶氨酸,相当于10 g乳清蛋白),年轻人在训练后的1.5 h蛋白代谢达到峰值,而老年人则要到训练后的3-5 h后达到高峰[58]。类似的研究还有Paddon-Jones等[30]所进行的实验,他令被试在半蹲抗阻训练中,给被试补充晶氨酸,在训练后5 h,老年被试和年轻被试所引起的肌肉合成代谢反应水平是相似的,而在训练后的前3 h内,年轻人的反应较老年被试明显得多。在非运动训练的研究中,给年轻人单纯补充乳清蛋白10 g可以明显增加肌肉蛋白合成,而20 g则达到一个平台期。有研究采用逐步补充乳清蛋白的方式,即在抗阻训练过程中逐天增加补充乳清蛋白的量(从10 g、20 g,一直可增加到40 g),结果被试肌肉蛋白合成代谢水平增长明显[29]。在补充蛋白的时间方面,Symons等[59]的研究是在老年人被试从事12周抗阻训练过程中,每次训练后立刻补充10 g乳清蛋白,结果发现被试肌纤维横断面积明显增粗和等动肌力明显增强,而训练后2 h补充乳清蛋白的被试则效果不如即刻补充的明显。关于补充蛋白时间的研究报道有许多,虽然结果不尽相同,但所揭示出的总规律是一致的,即在接近训练过程补充蛋白最为有效,而年轻人肌肉蛋白合成代谢对蛋白补充的敏感性显著高于老年人。"
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