Preclinical rodent models are essential research tools for improving understanding of physiological aging processes in humans. However, the translatability of findings obtained leveraging rodent models to humans is limited, likely due in part to differences in macronutrient composition of the diets. Here, we investigated the impact of a 3-month diet intervention in old male C57BL/6JN mice in which the macronutrient composition was aligned with that of a midlife/older adult in the United States, compared to a traditional rodent diet, and assessed various phenotypes that are typically altered with aging. Following the diet period, mice fed the human macronutrient-matched diet had greater quadricep and subcutaneous adipose and visceral adipose tissue masses compared to animals fed a traditional mouse diet. Frailty, assessed using a clinical frailty index, was lower, while grip strength was higher in mice fed the human-matched diet. Circulating metabolite and inflammatory cytokine profiles were altered in mice fed the human-matched diet. Notably, mortality rate (assessed in animals who died or were euthanized per veterinary recommendation before the pre-determined end of study euthanasia), tended to be lower in mice fed the human-matched diet. The present study underscores the importance of diet in rodent studies of aging, as differences in macronutrient composition can affect various physiological processes in old mice that are relevant to aging research.

临床前啮齿动物模型是提高对人类生理衰老过程的理解的重要研究工具。然而，利用啮齿动物模型获得的发现对人类的可转化性是有限的，这可能部分是由于饮食中宏量营养素成分的差异。在这里，我们调查了对老年雄性 C57BL/6JN 小鼠进行 3 个月饮食干预的影响，与传统啮齿动物饮食相比，其中宏量营养素成分与美国中年/老年人的宏量营养素组成一致，并评估了通常随着年龄增长而改变的各种表型。在饮食期之后，与饲喂传统小鼠饮食的动物相比，喂食人类宏量营养素匹配饮食的小鼠具有更大的股四头肌和皮下脂肪以及内脏脂肪组织肿块。使用临床衰弱指数评估的衰弱程度较低，而饲喂人类匹配饮食的小鼠的握力较高。在喂食人类匹配饮食的小鼠中，循环代谢物和炎性细胞因子谱发生改变。值得注意的是，在预先确定的研究安乐死结束之前，根据兽医建议死亡或被安乐死的动物的死亡率（在预先确定的研究结束安乐死之前评估）在喂食人类匹配饮食的小鼠中往往较低。本研究强调了饮食在啮齿动物衰老研究中的重要性，因为宏量营养素组成的差异会影响与衰老研究相关的老年小鼠的各种生理过程。