Aging is a complex physiological process that leads to the progressive decline of metabolic and immune function, among other biological mechanisms. As global life expectancy increases, it is important to understand determinants of healthy aging—including environmental and genetic factors—and thus slow the onset or progression of age-related disease. Environmental enrichment (EE) is a housing environment wherein laboratory animals engage with complex physical and social stimulation. EE is a prime model to understand environmental influences on aging dynamics, as it confers an antiobesity and anticancer phenotype that has been implicated in healthy aging and health span extension. Although EE is frequently used to study malignancies in young mice, fewer studies characterize EE-cancer outcomes in older mice. Here, we used young (3-month-old) and aged (14-month-old) female C57BL/6 mice to determine whether EE would be able to mitigate age-related deficiencies in metabolic function and thus alter Lewis lung carcinoma (LLC) growth. Overall, EE improved metabolic function, resulting in reduced fat mass, increased lean mass, and improved glycemic processing; many of these effects were stronger in the aged cohort than in the young cohort, indicating an age-driven effect on metabolic responses. In the aged-EE cohort, subcutaneously implanted LLC tumor growth was inhibited and tumors exhibited alterations in various markers of apoptosis, proliferation, angiogenesis, inflammation, and malignancy. These results validate EE as an anticancer model in aged mice and underscore the importance of understanding environmental influences on cancer malignancy in aged populations. Prevention Relevance: Environmental enrichment (EE) serves as a model of complex physical and social stimulation. This study validates EE as an anticancer intervention paradigm in aged mice and underscores the importance of understanding environmental influences on cancer malignancy in aged populations.

中文翻译：

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环境富集减轻老年雌性小鼠与年龄相关的代谢衰退和刘易斯肺癌的生长

衰老是一个复杂的生理过程，它会导致代谢和免疫功能的逐渐下降，以及其他生物学机制。随着全球预期寿命的增加，了解健康老龄化的决定因素（包括环境和遗传因素）从而减缓与年龄相关的疾病的发作或进展非常重要。环境富集 (EE) 是一种居住环境，其中实验动物参与复杂的身体和社会刺激。EE 是了解环境对衰老动态影响的主要模型，因为它赋予了与健康衰老和健康跨度延长有关的抗肥胖和抗癌表型。尽管 EE 经常用于研究年轻小鼠的恶性肿瘤，但很少有研究描述老年小鼠的 EE 癌症结果。这里，我们使用年轻（3 个月大）和老年（14 个月大）雌性 C57BL/6 小鼠来确定 EE 是否能够减轻与年龄相关的代谢功能缺陷，从而改变 Lewis 肺癌 (LLC) 的生长. 总体而言，EE 改善了代谢功能，从而减少了脂肪量、增加了瘦肉量并改善了血糖处理；许多这些影响在老年人群中比在年轻人群中更强，表明年龄驱动对代谢反应的影响。在老年 EE 队列中，皮下植入的 LLC 肿瘤生长受到抑制，肿瘤在凋亡、增殖、血管生成、炎症和恶性肿瘤的各种标志物中表现出改变。这些结果验证了 EE 作为老年小鼠的抗癌模型，并强调了了解环境对老年人癌症恶性肿瘤的影响的重要性。预防相关性：环境丰富（EE）是复杂的物理和社会刺激的模型。本研究验证了 EE 作为老年小鼠的抗癌干预范式，并强调了了解环境对老年人癌症恶性肿瘤的影响的重要性。