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

Hahn, O; Drews, LF; Nguyen, A; Tatsuta, T; Gkioni, L; Hendrich, O; Zhang, Q; ... Partridge, L; + view all (2019) A nutritional memory effect counteracts the benefits of dietary restriction in old mice. Nature Metabolism , 1 pp. 1059-1073. 10.1038/s42255-019-0121-0. Green open access

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Abstract

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.

Type: Article
Title: A nutritional memory effect counteracts the benefits of dietary restriction in old mice
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s42255-019-0121-0
Publisher version: https://doi.org/10.1038/s42255-019-0121-0
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Ageing, Fat metabolism
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10085239
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