Methionine Restriction Extends Lifespan in Progeroid Mice and Alters Lipid and Bile Acid Metabolism

被引：136

作者：

Barcena, Clea ^{[1
,2
]}

Quiros, Pedro M. ^{[1
,2
]}

Durand, Sylvere ^{[3
,4
,5
,6
]}

Mayoral, Pablo ^{[1
]}

Rodriguez, Francisco ^{[1
]}

Caravia, Xurde M. ^{[1
]}

Marino, Guillermo ^{[7
,8
]}

Garabaya, Cecilia ^{[1
]}

Teresa Fernandez-Garcia, Maria ^{[9
]}

Kroemer, Guido ^{[3
,4
,5
,6
,10
,11
,12
]}

Freije, Jose M. P. ^{[1
,2
]}

Lopez-Otin, Carlos ^{[1
,2
]}

机构：

[1] Univ Oviedo, Inst Univ Oncol IUOPA, Fac Med, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain

[2] Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain

[3] Cell Biol & Metabol Platforms, Gustave Roussy Canc Campus, Villejuif, France

[4] Ctr Rech Cordeliers, Equipe Labellisee Ligue Canc 11, Paris, France

[5] INSERM, U1138, Paris, France

[6] Univ Paris 05, Sorbonne Paris Cite, Paris, France

[7] IISPA, Grp Autofagia & Metab, Oviedo, Spain

[8] Univ Oviedo, Fac Med, Dept Biol Func, E-33006 Oviedo, Spain

[9] Univ Oviedo, IUOPA, Unidad Histopatol Mol, E-33006 Oviedo, Spain

[10] Univ Paris 06, Paris, France

[11] Hop Europeen Georges Pompidou, AP HP, Pole Biol, Paris, France

[12] Karolinska Inst, Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Stockholm, Sweden

来源：

CELL REPORTS | 2018年 / 24卷 / 09期

基金：

欧洲研究理事会;

关键词：

CALORIC RESTRICTION; DIETARY RESTRICTION; CELL-PROLIFERATION; LITHOCHOLIC ACID; BINDING-PROTEINS; SOMATOTROPH AXIS; DEFICIENT MICE; IN-VIVO; LONGEVITY; STRESS;

D O I：

10.1016/j.celrep.2018.07.089

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Dietary intervention constitutes a feasible approach for modulating metabolism and improving the health span and lifespan. Methionine restriction (MR) delays the appearance of age-related diseases and increases longevity in normal mice. However, the effect of MR on premature aging remains to be elucidated. Here, we describe that MR extends lifespan in two different mouse models of Hutchinson-Gilford progeria syndrome (HGPS) by reversing the transcriptome alterations in inflammation and DNA-damage response genes present in this condition. Further, MR improves the lipid profile and changes bile acid levels and conjugation, both in wild-type and in progeroid mice. Notably, treatment with cholic acid improves the health span and lifespan in vivo. These results suggest the existence of a metabolic pathway involved in the longevity extension achieved by MR and support the possibility of dietary interventions for treating progeria.

引用

页码：2392 / 2403

页数：12

共 58 条

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