Gene expression changes in cerebellum induced by dietary restriction

Lisanne J. van’t Sant, María B. Birkisdóttir, Rutger A. Ozinga, Ákos Gyenis, Jan H.J. Hoeijmakers, Wilbert P. Vermeij*, Dick Jaarsma*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Background: Dietary restriction (DR) is a well-established universal anti-aging intervention, and is neuroprotective in multiple models of nervous system disease, including models with cerebellar pathology. The beneficial effects of DR are associated with a rearrangement of gene expression that modulate metabolic and cytoprotective pathways. However, the effect of DR on the cerebellar transcriptome remained to be fully defined. Results: Here we analyzed the effect of a classical 30% DR protocol on the transcriptome of cerebellar cortex of young-adult male mice using RNAseq. We found that about 5% of expressed genes were differentially expressed in DR cerebellum, the far majority of whom showing subtle expression changes. A large proportion of down-regulated genes are implicated in signaling pathways, in particular pathways associated with neuronal signaling. DR up regulated pathways in large part were associated with cytoprotection and DNA repair. Analysis of the expression of cell-specific gene sets, indicated a strong enrichment of DR down genes in Purkinje cells, while genes specifically associated with granule cells did not show such a preferential down-regulation. Conclusion: Our data show that DR may have a clear effect on the cerebellar transcriptome inducing a mild shift from physiology towards maintenance and repair, and having cell-type specific effects.

Original languageEnglish
Article number1185665
JournalFrontiers in Molecular Neuroscience
Publication statusPublished - 24 May 2023

Bibliographical note

Funding Information:
We acknowledge financial support of the National Institute of Health (NIH)/National Institute of Aging (NIA) (AG17242), European Research Council Advanced Grants Dam2Age (to JH), ONCODE supported by the Dutch Cancer Society, ADPS Longevity Research Award (to WV), Memorabel (ZonMW 733050810), BBoL (NWO-ENW 737.016.015), Deutsche Forschungsgemeinschaft (DFG, German Research Foundation—Project-ID 73111208—SFB 829), Regiodeal Foodvalley (162135) and the European Joint Programme Rare Diseases (TC-NER RD20-113).

Publisher Copyright:
Copyright © 2023 van’t Sant, Birkisdóttir, Ozinga, Gyenis, Hoeijmakers, Vermeij and Jaarsma.


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