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Role of macrophages in age-related oxidative stress and lipofuscin accumulation in mice

机译：巨噬细胞在小鼠年龄相关的氧化应激和脂褐素积累中的作用

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Highlights ? Peritoneal macrophages from old mice have higher oxidant levels than lymphocytes. ? Long-lived mice have a well-preserved redox state in both macrophages and lymphocytes. ? Peritoneal macrophages have higher lipofuscin levels than lymphocytes along aging. The age-related changes in the immune functions (immunosenescence) may be mediated by an increase of oxidative stress and damage affecting leukocytes. Although the “oxidation-inflammation” theory of aging proposes that phagocytes are the main immune cells contributing to “oxi-inflamm-aging”, this idea has not been corroborated. The aim of this work was to characterize the age-related changes in several parameters of oxidative stress and immune function, as well as in lipofuscin accumulation (“a hallmark of aging”), in both total peritoneal leukocyte population and isolated peritoneal macrophages. Adult, mature, old and long-lived mice (7, 13, 18 and 30 months of age, respectively) were used. The xanthine oxidase (XO) activity-expression, basal levels of superoxide anion and ROS, catalase activity, oxidized (GSSG) and reduced (GSH) glutathione content and lipofuscin levels, as well as both phagocytosis and digestion capacity were evaluated. The results showed an age-related increase of oxidative stress and lipofuscin accumulation in murine peritoneal leukocytes, but especially in macrophages. Macrophages from old mice showed lower antioxidant defenses (catalase activity and GSH levels), higher oxidizing compounds (XO activity/expression and superoxide, ROS and GSSG levels) and lipofuscin levels, together with an impaired macrophage functions, in comparison to adults. In contrast, long-lived mice showed in their peritoneal leukocytes, and especially in macrophages, a well-preserved redox state and maintenance of their immune functions, all which could account for their high longevity. Interestingly, macrophages showed higher XO activity and lipofuscin accumulation than lymphocytes in all the ages analyzed. Our results support that macrophages play a central role in the chronic oxidative stress associated with aging, and the fact that phagocytes are key cells contributing to immunosenescence and “oxi-inflamm-aging”. Moreover, the determination of oxidative stress and immune function parameters, together with the lipofuscin quantification, in macrophages, can be used as useful markers of the rate of aging and longevity. Graphical Figure options
机译：强调 ？老年小鼠的腹膜巨噬细胞的氧化剂水平高于淋巴细胞。 ？长寿小鼠的巨噬细胞和淋巴细胞均具有良好的氧化还原状态。 ？沿衰老，腹膜巨噬细胞的脂褐素水平高于淋巴细胞。免疫功能（免疫衰老）的年龄相关变化可能是由氧化应激的增加和影响白细胞的损害所介导的。尽管衰老的“氧化-炎症”理论认为吞噬细胞是导致“氧化-炎症-衰老”的主要免疫细胞，但这一观点尚未得到证实。这项工作的目的是表征总腹膜白细胞群和孤立的腹膜巨噬细胞中氧化应激和免疫功能的几个参数以及脂褐素积聚（“衰老的标志”）中与年龄相关的变化。使用成年，成年，老年和长寿小鼠（分别为7、13、18和30个月大）。黄嘌呤氧化酶（XO）的活性表达，基础水平的超氧阴离子和ROS，过氧化氢酶活性，氧化（GSSG）和还原的（GSH）谷胱甘肽含量和脂褐素水平以及吞噬作用和消化能力均得到评估。结果显示，鼠腹膜白细胞，尤其是巨噬细胞中，氧化应激和脂褐素积累与年龄有关。与成年小鼠相比，成年小鼠的巨噬细胞显示出较低的抗氧化剂防御能力（​​过氧化氢酶活性和GSH水平），较高的氧化性化合物（XO活性/表达和超氧化物，ROS和GSSG水平）和脂褐素水平，以及巨噬细胞功能受损。相反，长寿小鼠的腹膜白细胞，特别是巨噬细胞，具有良好的氧化还原状态并维持其免疫功能，所有这些都可以说明它们的长寿。有趣的是，在所有年龄段中，巨噬细胞均比淋巴细胞显示更高的XO活性和脂褐素积累。我们的研究结果支持巨噬细胞在与衰老相关的慢性氧化应激中起着核心作用，而吞噬细胞是促成免疫衰老和“氧化-炎症-衰老”的关键细胞这一事实。此外，巨噬细胞中氧化应激和免疫功能参数的测定以及脂褐素的定量可以用作衰老和长寿率的有用标志。图形图形选项

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