A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms

被引:358
作者
Choi, In Young [1 ,2 ]
Piccio, Laura [3 ,4 ]
Childress, Patra [5 ]
Bollman, Bryan [3 ,4 ]
Ghosh, Arko [6 ]
Brandhorst, Sebastian [1 ,2 ]
Suarez, Jorge [1 ,2 ]
Michalsen, Andreas [7 ]
Cross, Anne H. [3 ,4 ]
Morgan, Todd E. [1 ,2 ]
Wei, Min [1 ,2 ]
Paul, Friedemann [8 ,9 ,10 ,11 ]
Bock, Markus [8 ,9 ,10 ,11 ]
Longo, Valter D. [1 ,2 ,6 ,12 ,13 ]
机构
[1] Univ So Calif, Sch Gerontol, Longev Inst, Los Angeles, CA 90089 USA
[2] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA
[3] Washington Univ, Sch Med, Dept Neurol & Neurosurg, St Louis, MO 63110 USA
[4] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO 63110 USA
[5] Univ So Calif, Keck Sch Med, Global Med Program, Los Angeles, CA 90089 USA
[6] Univ So Calif, Dana & David Dornsife Coll Letters Arts & Sci, Dept Neurosci, Los Angeles, CA 90089 USA
[7] Charite, Inst Social Med Epidemiol & Hlth Econ, D-10117 Berlin, Germany
[8] Charite, NeuroCure Clin Res Ctr, D-10117 Berlin, Germany
[9] Charite, Clin & Expt Multiple Sclerosis Res Ctr, Dept Neurol, D-10117 Berlin, Germany
[10] Fac Med Charite, Expt & Clin Res Ctr, D-10117 Berlin, Germany
[11] Max Delbruck Ctr Mol Med, D-10117 Berlin, Germany
[12] Univ So Calif, Keck Sch Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90089 USA
[13] FIRC Inst Mol Oncol, IFOM, I-20139 Milan, Italy
基金
美国国家卫生研究院;
关键词
CENTRAL-NERVOUS-SYSTEM; CALORIE RESTRICTION; ANIMAL-MODELS; T-CELLS; ENCEPHALOMYELITIS; LESIONS; GLUCOCORTICOIDS; DISEASE; OLIGODENDROCYTES; IMMUNOLOGY;
D O I
10.1016/j.celrep.2016.05.009
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Dietary interventions have not been effective in the treatment of multiple sclerosis (MS). Here, we show that periodic 3-day cycles of a fasting mimicking diet (FMD) are effective in ameliorating demyelination and symptoms in a murine experimental autoimmune encephalomyelitis (EAE) model. The FMD reduced clinical severity in all mice and completely reversed symptoms in 20% of animals. These improvements were associated with increased corticosterone levels and regulatory T (T-reg) cell numbers and reduced levels of pro-inflammatory cytokines, T(H)1 and T(H)17 cells, and antigen-presenting cells (APCs). Moreover, the FMD promoted oligodendrocyte precursor cell regeneration and remyelination in axons in both EAE and cuprizone MS models, supporting its effects on both suppression of autoimmunity and remyelination. We also report preliminary data suggesting that an FMD or a chronic ketogenic diet are safe, feasible, and potentially effective in the treatment of relapsing-remitting multiple sclerosis (RRMS) patients.
引用
收藏
页码:2136 / 2146
页数:11
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