Seals Douglas R, Bell Christopher
Department of Integrative Physiology, University of Colorado, Boulder, Colorado, USA.
Diabetes. 2004 Feb;53(2):276-84. doi: 10.2337/diabetes.53.2.276.
Primary aging in adult humans is associated with a progressive, tonic activation of the peripheral sympathetic nervous system (SNS). The purpose of this SNS activation and its physiological impact are, however, unknown. We hypothesize that the chronic stimulation of the SNS with aging is driven in part by a progressive accumulation of body fat. This "error" is sensed by the central nervous system via increases in adiposity-sensitive humoral signals (e.g., leptin, insulin) that cross the blood-brain barrier, activate subcortical areas involved in the regulation of energy balance (e.g., ventromedial hypothalamus), and stimulate SNS outflow to peripheral tissues. The SNS activation is intended to increase beta-adrenergic thermogenesis in order to expend excess energy as heat rather than by storage of fat. Recent evidence, however, indicates that these adjustments are not effective in augmenting energy expenditure with aging. Indeed, older sedentary adults demonstrate reduced, not increased, beta-adrenergic stimulation of metabolic rate because of reduced tissue responsiveness, presumably mediated by SNS-induced impairment of beta-adrenergic signaling. As a result, age-associated SNS activation, initiated as a consequence of accumulating adiposity with the intent of preventing further fat storage, ironically, may in time evolve into a potential mechanism contributing to the development of obesity with aging.
成年人类的原发性衰老与外周交感神经系统（SNS）的渐进性、持续性激活有关。然而，这种SNS激活的目的及其生理影响尚不清楚。我们假设，随着年龄增长，SNS的慢性刺激部分是由体脂的逐渐积累驱动的。中枢神经系统通过穿越血脑屏障的肥胖敏感性体液信号（如瘦素、胰岛素）增加来感知这种“误差”，这些信号激活参与能量平衡调节的皮质下区域（如下丘脑腹内侧核），并刺激SNS向外周组织的传出。SNS激活旨在增加β-肾上腺素能产热，以便将多余能量以热量形式消耗，而非通过储存脂肪。然而，最近的证据表明，这些调节在衰老过程中并不能有效增加能量消耗。事实上，久坐不动的老年人由于组织反应性降低，β-肾上腺素能对代谢率的刺激作用减弱而非增强，这可能是由SNS诱导的β-肾上腺素能信号传导受损介导的。因此，与年龄相关的SNS激活，最初是由于脂肪堆积而引发，目的是防止进一步储存脂肪，但具有讽刺意味的是，随着时间的推移，它可能会演变成一种导致衰老相关肥胖发展的潜在机制。
