Barbieri M, Rizzo M R, Manzella D, Paolisso G
Department of Geriatric Medicine and Metabolic Diseases, II University of Naples, I-80138 Naples, Italy.
Diabetes Metab Res Rev. 2001 Jan-Feb;17(1):19-26. doi: 10.1002/dmrr.178.
It is widely known that advancing age is associated with impaired glucose handling. A unifying hypothesis explaining the relationship between aging and insulin resistance might encompass four main pathways, namely: (a) anthropometric changes (relative and absolute increase in body fat combined with a decline in fat free mass) which could be the anatomic substrate for explaining the reduction in active metabolic tissue; (b) environmental causes, mainly diet style and physical activity; (c) neuro-hormonal variations [decline in plasma dehydroepandrosterone sulphate (DHEAS) and IGF-1]; and finally (d) the rise in oxidative stress. Indeed previous studies have also investigated the occurrence and the degree of insulin resistance in healthy centenarians. Such data demonstrated that age-related insulin resistance is not an obligatory finding in the elderly and that healthy centenarians have a preserved insulin action compared to aged subjects. Why insulin action is preserved in centenarians is still not known. Nevertheless, a possible approach to the question is to outline the centenarians' anthropometric, endocrine and metabolic characteristics in order to design a clinical picture of such metabolic "successful aging". According to the remodeling theory of age, the preserved insulin action in centenarians might be the net result of the continuous adaptation of the body to the deleterious changes that occur over time. Nevertheless, only future longitudinal studies specifically designed to investigate the relationship between extreme old age and degree of insulin sensitivity will provide a conclusive answer with regard to the pathophysiology of adaptive metabolic changes occurring in the elderly.
众所周知，年龄增长与葡萄糖代谢受损有关。一个解释衰老与胰岛素抵抗之间关系的统一假说可能包含四个主要途径，即：(a) 人体测量学变化（体脂相对和绝对增加，同时去脂体重下降），这可能是解释活跃代谢组织减少的解剖学基础；(b) 环境因素，主要是饮食方式和身体活动；(c) 神经激素变化 [血浆硫酸脱氢表雄酮 (DHEAS) 和胰岛素样生长因子-1 (IGF-1) 下降]；最后 (d) 氧化应激增加。事实上，先前的研究也调查了健康百岁老人中胰岛素抵抗的发生情况和程度。这些数据表明，与年龄相关的胰岛素抵抗在老年人中并非必然出现，与老年受试者相比，健康百岁老人具有保留的胰岛素作用。百岁老人的胰岛素作用为何得以保留仍不清楚。然而，解决这个问题的一种可能方法是概述百岁老人的人体测量学、内分泌和代谢特征，以便勾勒出这种代谢“成功衰老”的临床图景。根据年龄重塑理论，百岁老人保留的胰岛素作用可能是身体对随时间发生的有害变化持续适应的最终结果。然而，只有未来专门设计用于研究极端老年与胰岛素敏感性程度之间关系的纵向研究，才能就老年人适应性代谢变化的病理生理学提供确凿答案。
