A nutritional memory effect counteracts the benefits of dietary restriction in old mice

被引：79

作者：

Hahn, Oliver ^{[1
,2
,3
]}

Drews, Lisa F. ^{[1
]}

An Nguyen ^{[4
]}

Tatsuta, Takashi ^{[1
]}

Gkioni, Lisonia ^{[1
]}

Hendrich, Oliver ^{[1
]}

Zhang, Qifeng ^{[4
]}

Langer, Thomas ^{[1
]}

Pletcher, Scott ^{[5
,6
]}

Wakelam, Michael J. O. ^{[4
]}

Beyer, Andreas ^{[2
,7
]}

Groenke, Sebastian ^{[1
]}

Partridge, Linda ^{[1
,8
]}

机构：

[1] Max Planck Inst Biol Ageing, Cologne, Germany

[2] Univ Cologne, CECAD, Cellular Networks & Syst Biol, Cologne, Germany

[3] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA USA

[4] Babraham Inst, Inositide Lab, Cambridge, England

[5] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA

[6] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA

[7] Univ Cologne, Ctr Mol Med Cologne, Cologne, Germany

[8] UCL, Inst Hlth Ageing, Dept Genet Evolut & Environm, London, England

来源：

NATURE METABOLISM | 2019年 / 1卷 / 11期

基金：

欧洲研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

WHITE ADIPOSE-TISSUE; CALORIC RESTRICTION; BROWN; LONGEVITY; PHOSPHATIDYLCHOLINE; METABOLISM; CANCER; HEALTH; THERMOGENESIS; RETARDATION;

D O I：

10.1038/s42255-019-0121-0

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Dietary restriction (DR) during adulthood can greatly extend lifespan and improve metabolic health in diverse species. However, whether DR in mammals is still effective when applied for the first time at old age remains elusive. Here, we report results of a late-life DR-switch experiment using 800 mice. Female mice aged 24 months were switched from an ad libitum (AL) diet to DR or vice versa. Strikingly, the switch from DR to AL acutely increases mortality, whereas the switch from AL to DR causes only a weak and gradual increase in survival, suggesting the body has a memory of earlier nutrition. RNA sequencing in liver and brown and white adipose tissue (BAT and WAT, respectively) demonstrates a largely refractory transcriptional and metabolic response in fat tissue to DR after an AL diet, particularly in WAT, and a proinflammatory signature in aged preadipocytes, which is prevented by chronic DR feeding. Our results provide evidence for a 'nutritional memory' as a limiting factor for DR-induced longevity and metabolic remodelling of WAT in mammals.

引用

页码：1059 / +

页数：26

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