Brüünsgaard Helle, Pedersen Bente Klarlund
Department of Infectious Diseases M7641, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Immunol Allergy Clin North Am. 2003 Feb;23(1):15-39. doi: 10.1016/s0889-8561(02)00056-5.
Aging is associated with chronic low-grade increases in circulating levels of inflammatory markers. A wide range of environmental factors, including smoking, infections, and obesity, genetic factors, and the declining function of sex hormones may contribute to systemic low-grade inflammatory activity in older individuals. Age-associated disease may exacerbate this phenomenon. The multifunctional cytokines TNF-alpha and IL-6 have been associated with morbidity and mortality in the elderly. Evidence supports the direct role of TNF-alpha in the pathogeneses of atherosclerosis, type 2 DM, and AD in older individuals. Age-related increases in systemic levels of TNF-alpha could provide a unifying basis for these disorders. Furthermore, TNF-alpha induces a catabolic state that causes frailty. Circulating levels of IL-6 seem to be a strong risk factor for frailty in the elderly, which could reflect its association with increased production of TNF-alpha. IL-6 also may be a risk factor for thromboembolic complications. In healthy, elderly populations, high circulating levels of TNF-alpha and IL-6 predict mortality, independent of comorbidity, indicating that TNF-alpha and IL-6 cause morbidity and mortality. In cohorts of frail, older individuals, TNF-alpha and IL-6 also act as disease markers. Circulating levels of TNF-alpha seem to be the best predictor of mortality in frail, elderly populations with a high mortality rate, whereas IL-6 seems to be the strongest risk marker in healthy, elderly populations. This finding could reflect that in relatively healthy old populations the increase in circulating levels of IL-6 represent a systemic response to local proinflammatory activities; however, when age-related inflammatory diseases progress, levels of TNF-alpha increase in the circulation and become gradually a stronger risk marker than IL-6. In conclusion low-grade elevations in levels of circulating cytokines are strong independent risk factors of morbidity and mortality in the elderly, and lifestyle factors and comorbidities may modulate these levels. Exercise and dietary interventions may be possible strategies to decrease inflammatory activity and improve the health status of the elderly.
衰老与循环炎症标志物水平的慢性低度升高有关。多种环境因素，包括吸烟、感染和肥胖、遗传因素以及性激素功能的下降，可能导致老年人全身性低度炎症活动。与年龄相关的疾病可能会加剧这一现象。多功能细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）与老年人的发病率和死亡率有关。有证据支持TNF-α在老年人动脉粥样硬化、2型糖尿病和阿尔茨海默病发病机制中的直接作用。与年龄相关的全身TNF-α水平升高可能为这些疾病提供一个统一的基础。此外，TNF-α会诱导分解代谢状态，导致身体虚弱。IL-6的循环水平似乎是老年人身体虚弱的一个强有力的危险因素，这可能反映了它与TNF-α产生增加的关联。IL-6也可能是血栓栓塞并发症的危险因素。在健康的老年人群中，TNF-α和IL-6的高循环水平可预测死亡率，独立于合并症，表明TNF-α和IL-6会导致发病和死亡。在体弱的老年人群队列中，TNF-α和IL-6也作为疾病标志物。TNF-α的循环水平似乎是死亡率高的体弱老年人群中死亡率的最佳预测指标，而IL-6似乎是健康老年人群中最强的风险标志物。这一发现可能反映出，在相对健康的老年人群中，IL-6循环水平的升高代表了对局部促炎活动的全身反应；然而，当与年龄相关的炎症性疾病进展时，TNF-α在循环中的水平会升高，并逐渐成为比IL-6更强的风险标志物。总之，循环细胞因子水平的低度升高是老年人发病和死亡的强有力独立危险因素，生活方式因素和合并症可能会调节这些水平。运动和饮食干预可能是降低炎症活动和改善老年人健康状况的可行策略。
