Lutz Charles T, Quinn LeBris S
Department of Pathology and Laboratory Medicine, Department of Microbiology, Immunology, and Molecular Genetics, and the Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA.
Aging (Albany NY). 2012 Aug;4(8):535-46. doi: 10.18632/aging.100482.
Human aging is characterized by both physical and physiological frailty. A key feature of frailty, sarcopenia is the age-associated decline in skeletal muscle mass, strength, and endurance that characterize even the healthy elderly. Increases in adiposity, particularly in visceral adipose tissue, are almost universal in aging individuals and can contribute to sarcopenia and insulin resistance by increasing levels of inflammatory cytokines known collectively as adipokines. Aging also is associated with declines in adaptive and innate immunity, known as immune senescence, which are risk factors for cancer and all-cause mortality. The cytokine interleukin-15 (IL-15) is highly expressed in skeletal muscle tissue and declines in aging rodent models. IL-15 inhibits fat deposition and insulin resistance, is anabolic for skeletal muscle in certain situations, and is required for the development and survival of natural killer (NK) lymphocytes. We review the effect that adipokines and myokines have on NK cells, with special emphasis on IL-15. We posit that increased adipokine and decreased IL-15 levels during aging constitute a common mechanism for sarcopenia, obesity, and immune senescence.
人类衰老的特征是身体和生理上的虚弱。衰弱的一个关键特征是肌肉减少症，即与年龄相关的骨骼肌质量、力量和耐力下降，即使是健康的老年人也有此特征。肥胖增加，尤其是内脏脂肪组织的增加，在老年人中几乎普遍存在，并且通过增加统称为脂肪因子的炎症细胞因子水平，可导致肌肉减少症和胰岛素抵抗。衰老还与适应性免疫和先天性免疫的下降有关，即免疫衰老，这是癌症和全因死亡率的危险因素。细胞因子白细胞介素-15（IL-15）在骨骼肌组织中高度表达，在衰老的啮齿动物模型中表达下降。IL-15抑制脂肪沉积和胰岛素抵抗，在某些情况下对骨骼肌具有合成代谢作用，并且是自然杀伤（NK）淋巴细胞发育和存活所必需的。我们综述了脂肪因子和肌动蛋白对NK细胞的影响，特别强调了IL-15。我们认为，衰老过程中脂肪因子增加和IL-15水平降低是肌肉减少症、肥胖和免疫衰老的共同机制。
