Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
Nat Commun. 2024 Jun 18;15(1):5217. doi: 10.1038/s41467-024-49589-z.
Dietary protein is a critical regulator of metabolic health and aging. Low protein diets are associated with healthy aging in humans, and dietary protein restriction extends the lifespan and healthspan of mice. In this study, we examined the effect of protein restriction (PR) on metabolic health and the development and progression of Alzheimer's disease (AD) in the 3xTg mouse model of AD. Here, we show that PR promotes leanness and glycemic control in 3xTg mice, specifically rescuing the glucose intolerance of 3xTg females. PR induces sex-specific alterations in circulating and brain metabolites, downregulating sphingolipid subclasses in 3xTg females. PR also reduces AD pathology and mTORC1 activity, increases autophagy, and improves the cognition of 3xTg mice. Finally, PR improves the survival of 3xTg mice. Our results suggest that PR or pharmaceutical interventions that mimic the effects of this diet may hold promise as a treatment for AD.
饮食蛋白质是代谢健康和衰老的关键调节因子。低蛋白饮食与人类的健康衰老有关，而饮食蛋白质限制延长了小鼠的寿命和健康寿命。在这项研究中，我们研究了蛋白质限制（PR）对 AD 3xTg 小鼠模型的代谢健康以及阿尔茨海默病（AD）的发展和进展的影响。在这里，我们表明 PR 促进了 3xTg 小鼠的苗条和血糖控制，特别是纠正了 3xTg 雌性的葡萄糖不耐受。PR 诱导了循环和大脑代谢物的性别特异性改变，下调了 3xTg 雌性的鞘脂亚类。PR 还减少了 AD 病理和 mTORC1 活性，增加了自噬，并改善了 3xTg 小鼠的认知能力。最后，PR 提高了 3xTg 小鼠的存活率。我们的结果表明，PR 或模仿这种饮食效果的药物干预可能有望成为 AD 的治疗方法。
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