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.
Preview |
Text (Article)
Wright article_1-2.pdf - Accepted Version Download (813kB) | Preview |
Preview |
Spreadsheet (Spreadsheet)
Wright Supplementary Table 1-4.pdf - Accepted Version Download (560kB) | Preview |
Preview |
Spreadsheet
Wright Supplementary Table 5.pdf - Accepted Version Download (317kB) | Preview |
Preview |
Image (Figure 1)
Wright figure_1.pdf - Accepted Version Download (197kB) | Preview |
Preview |
Image (Figure 2)
Wright figure_2.pdf - Accepted Version Download (24kB) | Preview |
Preview |
Image (Figure 3)
Wright figure_3.pdf - Accepted Version Download (1MB) | Preview |
Preview |
Image (Figure 4)
Wright figure_4.pdf - Accepted Version Download (490kB) | Preview |
Preview |
Image (Figure 5)
Wright figure_5.pdf - Accepted Version Download (712kB) | Preview |
Preview |
Image (Figure 6)
Wright figure_6.pdf - Accepted Version Download (523kB) | Preview |
Preview |
Image (Figure 7)
Wright figure_7.pdf - Accepted Version Download (69kB) | Preview |
Preview |
Image (Figure 8)
figure_8.tif - Accepted Version Download (282kB) | Preview |
Preview |
Image (Figure 9)
figure_9.tif - Accepted Version Download (10MB) | Preview |
Preview |
Image (Figure 10)
figure_10.tif - Accepted Version Download (8MB) | Preview |
Preview |
Image (Figure 11)
figure_11.tif - Accepted Version Download (888kB) | Preview |
Preview |
Image (Figure 12)
figure_12.tif - Accepted Version Download (128kB) | Preview |
Preview |
Image (Figure 13)
figure_13.tif - Accepted Version Download (26MB) | Preview |
Preview |
Image (Figure 14)
figure_14.tif - Accepted Version Download (659kB) | Preview |
Preview |
Image (Figure 15)
figure_15.tif - Accepted Version Download (1MB) | Preview |
Preview |
Image (Figure 16)
figure_16.tif - Accepted Version Download (11MB) | Preview |
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.
Archive Staff Only
 |
View Item |
