A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan.
A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan.
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DOI：
10.1016/j.cmet.2015.05.012
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发表时间：
2015-07-07
期刊：
影响因子：
29
通讯作者：
Longo VD
中科院分区：
文献类型：
--
作者：
Brandhorst S;Choi IY;Wei M;Cheng CW;Sedrakyan S;Navarrete G;Dubeau L;Yap LP;Park R;Vinciguerra M;Di Biase S;Mirzaei H;Mirisola MG;Childress P;Ji L;Groshen S;Penna F;Odetti P;Perin L;Conti PS;Ikeno Y;Kennedy BK;Cohen P;Morgan TE;Dorff TB;Longo VD
长时间禁食(PF)可提高抗应激能力，但其对长寿的影响却知之甚少。我们表明，交替的PF和营养丰富的培养基延长了酵母的寿命，而不依赖于已建立的长寿基因。在小鼠中，四天的饮食模拟禁食(FMD)，以最大限度地减少PF的负担，减少了多个器官/系统的大小；随着祖细胞和干细胞数量的增加和再生，这种效果随之而来。两个月一次的FMD周期从中年开始，可以延长寿命，降低内脏脂肪，减少癌症发病率和皮肤损害，恢复免疫系统，并延缓骨密度损失。在老年小鼠中，FMD循环促进了海马神经发生，降低了IGF-1水平和PKA活性，提高了NeuroD1，并改善了认知能力。在一项试点临床试验中，三个FMD周期降低了衰老、糖尿病、心血管疾病和癌症的风险因素/生物标记物，没有重大不良影响，为使用FMD促进健康提供了支持。
Prolonged fasting (PF) promotes stress resistance but its effects on longevity are poorly understood. We show that alternating PF and nutrient-rich medium extended yeast lifespan independently of established pro-longevity genes. In mice, four days of a diet that mimics fasting (FMD), developed to minimize the burden of PF, decreased the size of multiple organs/systems; an effect followed upon re-feeding by an elevated number of progenitor and stem cells and regeneration. Bi-monthly FMD cycles started at middle age extended longevity, lowered visceral fat, reduced cancer incidence and skin lesions, rejuvenated the immune system, and retarded bone mineral density loss. In old mice, FMD cycles promoted hippocampal neurogenesis, lowered IGF-1 levels and PKA activity, elevated NeuroD1, and improved cognitive performance. In a pilot clinical trial, three FMD cycles decreased risk factors/biomarkers for aging, diabetes, cardiovascular disease and cancer without major adverse effects, providing support for the use of FMDs to promote healthspan.