title: Transcriptome analysis in calorie-restricted rats implicates epigenetic and post-translational mechanisms in neuroprotection and aging.
abstract: BACKGROUND
  Caloric restriction (CR) can increase longevity in rodents and improve memory function in humans. α-Lipoic acid (LA) has been shown to improve memory function in rats, but not longevity. While studies have looked at survival in rodents after switching from one diet to another, the underlying mechanisms of the beneficial effects of CR and LA supplementation are unknown. Here, we use RNA-seq in cerebral cortex from rats subjected to CR and LA-supplemented rats to understand how changes in diet can affect aging, neurodegeneration and longevity.
  
  
  RESULTS
  Gene expression changes during aging in ad libitum-fed rats are largely prevented by CR, and neuroprotective genes are overexpressed in response to both CR and LA diets with a strong overlap of differentially expressed genes between the two diets. Moreover, a number of genes are differentially expressed specifically in rat cohorts exhibiting diet-induced life extension. Finally, we observe that LA supplementation inhibits histone deacetylase (HDAC) protein activity in vitro in rat astrocytes. We find a single microRNA, miR-98-3p, that is overexpressed during CR feeding and LA dietary supplementation; this microRNA alters HDAC and histone acetyltransferase (HAT) activity, which suggests a role for HAT/HDAC homeostasis in neuroprotection.
  
  
  CONCLUSIONS
  This study presents extensive data on the effects of diet and aging on the cerebral cortex transcriptome, and also emphasises the importance of epigenetics and post-translational modifications in longevity and neuroprotection.
authors.affiliation: Integrative Genomics of Ageing Group, Institute of Integrative Biology, University of Liverpool, Liverpool, UK.
authors.forename: Shona H
authors.initials: SH
authors.lastname: Wood
authors.affiliation: Integrative Genomics of Ageing Group, Institute of Integrative Biology, University of Liverpool, Liverpool, UK.
authors.forename: Sipko
authors.initials: S
authors.lastname: van Dam
authors.affiliation: Integrative Genomics of Ageing Group, Institute of Integrative Biology, University of Liverpool, Liverpool, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Craig
authors.affiliation: Integrative Genomics of Ageing Group, Institute of Integrative Biology, University of Liverpool, Liverpool, UK.
authors.forename: Robi
authors.initials: R
authors.lastname: Tacutu
authors.affiliation: Integrative Genomics of Ageing Group, Institute of Integrative Biology, University of Liverpool, Liverpool, UK.
authors.forename: Amy
authors.initials: A
authors.lastname: O'Toole
authors.affiliation: Integrative Genomics of Ageing Group, Institute of Integrative Biology, University of Liverpool, Liverpool, UK.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Merry
authors.affiliation: Integrative Genomics of Ageing Group, Institute of Integrative Biology, University of Liverpool, Liverpool, UK. jp@senescence.info.
authors.forename: João Pedro
authors.initials: JP
authors.lastname: de Magalhães
mesh_terms: D000818:Animals; D031204:Caloric Restriction; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D044127:Epigenesis, Genetic; D051548:Histone Acetyltransferases / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D008136:Longevity; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D008063:Thioctic Acid / Q000494:pharmacology; D059467:Transcriptome
chemical_list: D008063:Thioctic Acid; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases