PMID- 26694192
OWN - NLM
STAT- MEDLINE
DCOM- 20160627
LR  - 20240324
IS  - 1474-760X (Electronic)
IS  - 1474-7596 (Print)
IS  - 1474-7596 (Linking)
VI  - 16
DP  - 2015 Dec 22
TI  - Transcriptome analysis in calorie-restricted rats implicates epigenetic and 
      post-translational mechanisms in neuroprotection and aging.
PG  - 285
LID - 10.1186/s13059-015-0847-2 [doi]
LID - 285
AB  - BACKGROUND: Caloric restriction (CR) can increase longevity in rodents and 
      improve memory function in humans. alpha-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.
FAU - Wood, Shona H
AU  - Wood SH
AD  - Integrative Genomics of Ageing Group, Institute of Integrative Biology, 
      University of Liverpool, Liverpool, UK.
FAU - van Dam, Sipko
AU  - van Dam S
AD  - Integrative Genomics of Ageing Group, Institute of Integrative Biology, 
      University of Liverpool, Liverpool, UK.
FAU - Craig, Thomas
AU  - Craig T
AD  - Integrative Genomics of Ageing Group, Institute of Integrative Biology, 
      University of Liverpool, Liverpool, UK.
FAU - Tacutu, Robi
AU  - Tacutu R
AD  - Integrative Genomics of Ageing Group, Institute of Integrative Biology, 
      University of Liverpool, Liverpool, UK.
FAU - O'Toole, Amy
AU  - O'Toole A
AD  - Integrative Genomics of Ageing Group, Institute of Integrative Biology, 
      University of Liverpool, Liverpool, UK.
FAU - Merry, Brian J
AU  - Merry BJ
AD  - Integrative Genomics of Ageing Group, Institute of Integrative Biology, 
      University of Liverpool, Liverpool, UK.
FAU - de Magalhaes, Joao Pedro
AU  - de Magalhaes JP
AD  - Integrative Genomics of Ageing Group, Institute of Integrative Biology, 
      University of Liverpool, Liverpool, UK. jp@senescence.info.
LA  - eng
GR  - BB/H008497/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - ERA164170/Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151222
PL  - England
TA  - Genome Biol
JT  - Genome biology
JID - 100960660
RN  - 73Y7P0K73Y (Thioctic Acid)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Animals
MH  - *Caloric Restriction
MH  - Cerebral Cortex/drug effects/growth & development/*metabolism
MH  - *Epigenesis, Genetic
MH  - Histone Acetyltransferases/metabolism
MH  - Histone Deacetylases/metabolism
MH  - *Longevity
MH  - Male
MH  - Rats
MH  - Rats, Inbred BN
MH  - Thioctic Acid/pharmacology
MH  - *Transcriptome
PMC - PMC4699360
EDAT- 2015/12/24 06:00
MHDA- 2016/06/28 06:00
PMCR- 2015/12/22
CRDT- 2015/12/24 06:00
PHST- 2015/07/09 00:00 [received]
PHST- 2015/11/27 00:00 [accepted]
PHST- 2015/12/24 06:00 [entrez]
PHST- 2015/12/24 06:00 [pubmed]
PHST- 2016/06/28 06:00 [medline]
PHST- 2015/12/22 00:00 [pmc-release]
AID - 10.1186/s13059-015-0847-2 [pii]
AID - 847 [pii]
AID - 10.1186/s13059-015-0847-2 [doi]
PST - epublish
SO  - Genome Biol. 2015 Dec 22;16:285. doi: 10.1186/s13059-015-0847-2.