异亮氨酸的饮食限制增加了遗传异质小鼠的健康寿命和寿命。

Cara L Green, Michaela E Trautman, Krittisak Chaiyakul, Raghav Jain, Yasmine H Alam, Reji Babygirija, Heidi H Pak, Michelle M Sonsalla, Mariah F Calubag, Chung-Yang Yeh, Anneliese Bleicher, Grace Novak, Teresa T Liu, Sarah Newman, Will A Ricke, Kristina A Matkowskyj, Irene M Ong, Cholsoon Jang, Judith Simcox, Dudley W Lamming
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引用次数: 0

摘要

低蛋白饮食可以促进不同物种的健康和长寿。支链氨基酸(BCAAs)亮氨酸、异亮氨酸和缬氨酸的限制在年轻C57BL/6J小鼠中概括了许多这些益处。限制饮食中的异亮氨酸(IleR)足以促进代谢健康,并且是C57BL/6J雄性低蛋白饮食的许多益处所必需的。在这里,我们检验了IleR将促进遗传异质性成年UM-HET3小鼠健康衰老的假设。我们发现IleR改善了年轻和老年HET3小鼠的代谢健康,促进了两性的瘦度和血糖控制,并以性别特异性的方式重新编程肝脏代谢。IleR可以减少雄性和雌性小鼠的虚弱,延长它们的寿命,但在雄性小鼠中的作用更大。我们的研究结果表明,IleR可以增加遗传多样性小鼠的健康寿命和寿命,并表明IleR或模拟这种效果的药物可能具有保护性干预的潜力。
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Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice.

Low-protein diets promote health and longevity in diverse species. Restriction of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine recapitulates many of these benefits in young C57BL/6J mice. Restriction of dietary isoleucine (IleR) is sufficient to promote metabolic health and is required for many benefits of a low-protein diet in C57BL/6J males. Here, we test the hypothesis that IleR will promote healthy aging in genetically heterogeneous adult UM-HET3 mice. We find that IleR improves metabolic health in young and old HET3 mice, promoting leanness and glycemic control in both sexes, and reprograms hepatic metabolism in a sex-specific manner. IleR reduces frailty and extends the lifespan of male and female mice, but to a greater degree in males. Our results demonstrate that IleR increases healthspan and longevity in genetically diverse mice and suggests that IleR, or pharmaceuticals that mimic this effect, may have potential as a geroprotective intervention.

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