A nutritional memory effect counteracts benefits of dietary restriction in old mice
| Autor: | Sebastian Grönke, An Nguyen, Andreas Beyer, Lisa F Drews, Oliver Hendrich, Linda Partridge, Oliver Hahn, Michael J.O. Wakelam, Takashi Tatsuta, Lisonia Gkioni, Thomas Langer, Scott D. Pletcher, Qifeng Zhang |
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| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism media_common.quotation_subject Longevity Adipose tissue Lipid metabolism Cell Biology White adipose tissue Biology Proinflammatory cytokine Endocrinology Ageing Physiology (medical) Internal medicine Internal Medicine medicine Gradual increase Metabolic health media_common |
| Zdroj: | Nat Metab |
| Popis: | 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. Dietary restriction (DR) late in life does not improve survival and has little benefit in metabolic health in mice. The absence of a DR gene-expression signature in fat tissue suggests that a ‘nutritional memory’ interferes with the benefits of DR. |
| Databáze: | OpenAIRE |
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