Carter Christy S, Onder Graziano, Kritchevsky Stephen B, Pahor Marco
University of Florida, Department of Aging and Geriatric Research, 1329 SW 16th St. PO Box 100143, Gainesville FL, 32610-0143, USA.
J Gerontol A Biol Sci Med Sci. 2005 Nov;60(11):1437-46. doi: 10.1093/gerona/60.11.1437.
The disablement process is often accompanied by sarcopenia or muscle loss, which is associated with virtually all identified disability risk factors. Clinically, the association between body composition and physical performance has been documented by several studies. However, loss of strength is greater than loss of muscle mass with age implying that the quality of remaining muscle may be reduced. Although there are limited data explaining potential physiological mechanisms that contribute to muscle quality, sarcopenia is frequently associated with fat accumulation, and the percentage of body fat increases with age even if weight does not. However, the relationship between fat and muscle function may not be linear, suggesting that there may be an optimal ratio of lean to fat mass for physical function. There are no definitive pharmacological interventions proven to prevent decline in physical function either by modulating body composition or by other means. One exception may be angiotensin-converting enzyme inhibitors (ACEIs). ACE is an important component of the renin-angiotensin system, the central hormonal regulator of blood pressure. Recent evidence suggests that ACEIs may improve physical function by means of direct effects on body composition in older persons, rather than through its blood-pressure-lowering effects. Clinical and genetic studies in humans and experimental evidence in animals suggest that modulation of the renin-angiotensin system is associated with metabolic and biochemical changes in skeletal muscle and fat, changes that are associated with declining physical function. ACEIs may modulate this process through a variety of molecular mechanisms including their influence on oxidative stress and on metabolic and inflammation pathways. This review describes potential biological mechanisms of ACE inhibition and its contribution to declining physical performance and changing body composition. Promising pharmacoepidemiological studies and experimental evidence in animals suggest that there are appropriate models in which to study this effect.
失能过程通常伴随着肌肉减少症或肌肉流失，这几乎与所有已确定的失能风险因素都有关联。临床上，多项研究已证实身体成分与身体机能之间的关联。然而，随着年龄增长，力量的丧失大于肌肉量的减少，这意味着剩余肌肉的质量可能会下降。尽管解释导致肌肉质量下降的潜在生理机制的数据有限，但肌肉减少症常与脂肪堆积相关，即使体重不变，体脂百分比也会随着年龄增长而增加。然而，脂肪与肌肉功能之间的关系可能并非线性，这表明身体机能可能存在一个最佳的瘦体重与脂肪量比例。目前尚无确凿的药物干预措施被证明可通过调节身体成分或其他方式来预防身体机能下降。一个例外可能是血管紧张素转换酶抑制剂（ACEIs）。ACE是肾素-血管紧张素系统的重要组成部分，该系统是血压的核心激素调节系统。最近的证据表明，ACEIs可能通过对老年人身体成分的直接作用来改善身体机能，而非通过其降压作用。人类的临床和遗传学研究以及动物实验证据表明，肾素-血管紧张素系统的调节与骨骼肌和脂肪的代谢及生化变化有关，这些变化与身体机能下降相关。ACEIs可能通过多种分子机制调节这一过程，包括其对氧化应激以及代谢和炎症途径的影响。本综述描述了ACE抑制的潜在生物学机制及其对身体机能下降和身体成分变化的影响。有前景的药物流行病学研究和动物实验证据表明，存在合适的模型来研究这种效应。
