PMID- 28768896
OWN - NLM
STAT- MEDLINE
DCOM- 20180424
LR  - 20220129
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 9
IP  - 7
DP  - 2017 Jul 31
TI  - The effects of graded levels of calorie restriction: XI. Evaluation of the main 
      hypotheses underpinning the life extension effects of CR using the hepatic 
      transcriptome.
PG  - 1770-1824
LID - 10.18632/aging.101269 [doi]
AB  - Calorie restriction (CR) may extend longevity by modulating the mechanisms 
      involved in aging. Different hypotheses have been proposed for its main mode of 
      action. We quantified hepatic transcripts of male C57BL/6 mice exposed to graded 
      levels of CR (0% to 40% CR) for three months, and evaluated the responses 
      relative to these various hypotheses. Of the four main signaling pathways implied 
      to be linked to the impact of CR on lifespan (insulin/insulin like growth factor 
      1 (IGF-1), nuclear factor-kappa beta (NF-kB), mechanistic target of rapamycin 
      (mTOR) and sirtuins (SIRTs)), all the pathways except SIRT were altered in a 
      manner consistent with increased lifespan. However, the expression levels of 
      SIRT4 and SIRT7 were decreased with increasing levels of CR. Changes consistent 
      with altered fuel utilization under CR may reduce reactive oxygen species 
      production, which was paralleled by reduced protection. Downregulated major 
      urinary protein (MUP) transcription suggested reduced reproductive investment. 
      Graded CR had a positive effect on autophagy and xenobiotic metabolism, and was 
      protective with respect to cancer signaling. CR had no significant effect on 
      fibroblast growth factor-21 (FGF21) transcription but affected transcription in 
      the hydrogen sulfide production pathway. Responses to CR were consistent with 
      several different hypotheses, and the benefits of CR on lifespan likely reflect 
      the combined impact on multiple aging related processes.
FAU - Derous, Davina
AU  - Derous D
AD  - Institute of Biological and Environmental Sciences, University of Aberdeen, 
      Aberdeen, Scotland, UK.
AD  - Centre for Genome Enabled Biology and Medicine, University of Aberdeen, Aberdeen, 
      Scotland, UK.
FAU - Mitchell, Sharon E
AU  - Mitchell SE
AD  - Institute of Biological and Environmental Sciences, University of Aberdeen, 
      Aberdeen, Scotland, UK.
FAU - Wang, Lu
AU  - Wang L
AD  - State Key laboratory of Molecular Developmental Biology, Institute of Genetics 
      and Developmental Biology, Chinese Academy of Sciences, Chaoyang, Beijing, China.
FAU - Green, Cara L
AU  - Green CL
AD  - Institute of Biological and Environmental Sciences, University of Aberdeen, 
      Aberdeen, Scotland, UK.
FAU - Wang, Yingchun
AU  - Wang Y
AD  - State Key laboratory of Molecular Developmental Biology, Institute of Genetics 
      and Developmental Biology, Chinese Academy of Sciences, Chaoyang, Beijing, China.
FAU - Chen, Luonan
AU  - Chen L
AD  - Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese 
      Academy of Sciences-Max Planck Partner Institute for Computational Biology, 
      Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 
      Shanghai, China.
FAU - Han, Jing-Dong J
AU  - Han JJ
AD  - Key laboratory of Systems Biology, Innovation Center for Cell Signaling Network, 
      Institute of Biochemistry and Cell Biology, Shanghai Institute of Biological 
      Sciences, Chinese Academy of Sciences, Shanghai, China.
FAU - Promislow, Daniel E L
AU  - Promislow DEL
AD  - Department of Pathology, University of Washington, Seattle, WA 98195, USA.
AD  - Department of Biology, University of Washington, Seattle, WA 98195, USA.
FAU - Lusseau, David
AU  - Lusseau D
AD  - Institute of Biological and Environmental Sciences, University of Aberdeen, 
      Aberdeen, Scotland, UK.
FAU - Douglas, Alex
AU  - Douglas A
AD  - Institute of Biological and Environmental Sciences, University of Aberdeen, 
      Aberdeen, Scotland, UK.
AD  - Centre for Genome Enabled Biology and Medicine, University of Aberdeen, Aberdeen, 
      Scotland, UK.
FAU - Speakman, John R
AU  - Speakman JR
AD  - Institute of Biological and Environmental Sciences, University of Aberdeen, 
      Aberdeen, Scotland, UK.
AD  - State Key laboratory of Molecular Developmental Biology, Institute of Genetics 
      and Developmental Biology, Chinese Academy of Sciences, Chaoyang, Beijing, China.
LA  - eng
GR  - BB/G009953/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
SB  - IM
MH  - Animal Feed/analysis
MH  - Animals
MH  - *Caloric Restriction
MH  - Gene Expression Regulation
MH  - Life Expectancy
MH  - Longevity/*drug effects/genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
PMC - PMC5559174
OTO - NOTNLM
OT  - aging
OT  - calorie restriction
OT  - gene expression
OT  - liver
OT  - transcriptomics
COIS- CONFLICTS OF INTEREST Authors declare no conflict of interest.
EDAT- 2017/08/05 06:00
MHDA- 2018/04/25 06:00
PMCR- 2017/07/01
CRDT- 2017/08/04 06:00
PHST- 2017/04/27 00:00 [received]
PHST- 2017/07/27 00:00 [accepted]
PHST- 2017/08/04 06:00 [entrez]
PHST- 2017/08/05 06:00 [pubmed]
PHST- 2018/04/25 06:00 [medline]
PHST- 2017/07/01 00:00 [pmc-release]
AID - 101269 [pii]
AID - 10.18632/aging.101269 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2017 Jul 31;9(7):1770-1824. doi: 10.18632/aging.101269.