Rxivist logo

A nutritional memory impairs survival, transcriptional and metabolic response to dietary restriction in old mice

By Oliver Hahn, Lisa F. Drews, An Nguyen, Takashi Tatsuta, Lisonia Gkioni, Oliver Hendrich, Qifeng Zhang, Thomas Langer, Scott Pletcher, Michael J. O. Wakelam, Andreas Beyer, Sebastian Grönke, Linda Partridge

Posted 09 Aug 2019
bioRxiv DOI: 10.1101/730853

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 conducted a late-life DR switch experiment employing 800 mice, by switching old animals from ad libitum (AL) to DR and vice versa. Strikingly, the switch from DR-to-AL acutely increased mortality, while the switch from AL-to-DR caused only a weak and gradual increase in survival, highlighting a memory of earlier nutrition. A significant association between fat preservation and survival response pointed to the white adipose tissue (WAT) as a potential memory source. Consistently, post-switch RNA-seq profiling in liver and WAT demonstrated that the transcriptional and metabolic program of chronic DR remained largely refractory to the AL-to-DR switch specifically in adipose tissue. Integration of lipidomics confirmed impaired membrane lipogenesis and limited mitochondrial copy number increase under late-life DR as functional consequences of this memory effect. Together, our results provide evidence for a nutritional memory as a limiting factor for DR-induced longevity and metabolic remodeling of WAT in mammals.

Download data

  • Downloaded 572 times
  • Download rankings, all-time:
    • Site-wide: 21,855 out of 77,930
    • In physiology: 108 out of 1,018
  • Year to date:
    • Site-wide: 36,608 out of 77,930
  • Since beginning of last month:
    • Site-wide: 37,502 out of 77,930

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)