Division of Diabetes and Aging, Department of Geriatrics, Mount Sinai School of Medicine, New York, NY 10029, USA.
Semin Nephrol. 2009 Nov;29(6):594-603. doi: 10.1016/j.semnephrol.2009.07.013.
Aging is characterized by increasing inflammation and oxidant stress (OS). Reduced renal function was present in more than 20% of normal-aged individuals sampled in the National Health and Nutrition Examination Survey (NHANES) cross-sectional study of the US population. Longitudinal studies in the United States and Italy showed that renal function does not decline in some individuals, suggesting that a search for causes of the loss of renal function in some persons might be indicated and interventions to reduce this outcome should be sought. Because advanced glycation end products (AGEs) induce both inflammation and OS, accumulate with age, and primarily are excreted by the kidney, one outcome of reduced renal function in aging could be decreased AGE disposal. The build-up of AGEs with reduced renal function could contribute to inflammation, increased oxidant stress, and accumulation of AGEs in aging. In fact, results from a longitudinal study of normal aging adults in Italy showed that the most significant correlation with mortality was the level of renal function. A clear link between inflammation, OS, AGEs, and chronic disease was shown in studies of mice that showed that reduction of AGE levels by drugs or decreased intake of AGEs reduces chronic kidney disease (CKD) and cardiovascular disease of aging. The data support a role for AGEs in the development of renal lesions in aging mice and reveal that AGEs in the diet are very important contributors to renal and cardiovascular lesions. AGEs signal through two receptors, one of which is anti-inflammatory (AGER1) and the other is proinflammatory (RAGE). Overexpression of AGER1 protects against OS and acute vascular injury. The reduction of AGEs in the diet is as efficient in preventing aging-related cardiovascular and renal lesions in mice as that seen with calorie restriction. Studies in normal adults of all ages and those with CKD suggest that the findings in mice may be directly applicable to both aging and CKD. Namely, the dietary content of AGEs determines the serum levels of AGEs and inflammatory mediators and urine AGE levels in both normal subjects and CKD patients. Importantly, reduction of AGEs controls these changes in both normal subjects and CKD patients, and the phenotypic changes in AGER1 are reduced in CKD patients by decreasing the amount of AGEs consumed with the diet. These data suggest that the changes in renal function in normal aging may be subject to control and this subject deserves renewed attention.
衰老是一个以炎症和氧化应激（OS）增加为特征的过程。在参与美国国家健康和营养检查调查（NHANES）的正常老年人的横断面研究中，超过 20%的个体存在肾功能下降。在美国和意大利进行的纵向研究表明，在一些个体中肾功能不会下降，这表明可能需要寻找导致某些个体肾功能丧失的原因，并寻求减少这种结果的干预措施。由于晚期糖基化终产物（AGEs）会引起炎症和 OS，并且随着年龄的增长而积累，主要通过肾脏排泄，因此衰老过程中肾功能下降的一个结果可能是 AGE 处理能力降低。随着肾功能下降，AGE 的积累可能会导致炎症、氧化应激增加以及衰老过程中 AGE 的积累。事实上，意大利一项针对正常老年成年人的纵向研究结果表明，与死亡率最显著相关的是肾功能水平。在对小鼠的研究中表明，AGE 水平的药物降低或 AGE 摄入减少可减少衰老相关的慢性肾脏病（CKD）和心血管疾病，从而明确了炎症、OS、AGEs 和慢性疾病之间的联系。这些数据支持 AGEs 在衰老小鼠肾脏病变中的作用，并揭示了饮食中的 AGEs 是导致肾脏和心血管病变的重要因素。AGEs 通过两种受体发出信号，其中一种是抗炎性的（AGER1），另一种是促炎性的（RAGE）。AGER1 的过度表达可防止 OS 和急性血管损伤。饮食中 AGE 减少在预防小鼠衰老相关心血管和肾脏病变方面的效率与热量限制一样高。对所有年龄段的正常成年人和 CKD 患者的研究表明，小鼠研究中的发现可能直接适用于衰老和 CKD。即，饮食中 AGEs 的含量决定了正常人和 CKD 患者的血清 AGEs 和炎症介质以及尿液 AGE 水平。重要的是，减少 AGEs 可控制正常人和 CKD 患者的这些变化，并且通过减少饮食中消耗的 AGEs 量，可减少 CKD 患者中 AGER1 的表型变化。这些数据表明，正常衰老过程中肾功能的变化可能受到控制，这个问题值得重新关注。
