PMID- 19968875
OWN - NLM
STAT- MEDLINE
DCOM- 20100118
LR  - 20211020
IS  - 1471-2164 (Electronic)
IS  - 1471-2164 (Linking)
VI  - 10
DP  - 2009 Dec 7
TI  - Genes and gene expression modules associated with caloric restriction and aging 
      in the laboratory mouse.
PG  - 585
LID - 10.1186/1471-2164-10-585 [doi]
AB  - BACKGROUND: Caloric restriction (CR) counters deleterious effects of aging and, 
      for most mouse genotypes, increases mean and maximum lifespan. Previous analyses 
      of microarray data have identified gene expression responses to CR that are 
      shared among multiple mouse tissues, including the activation of anti-oxidant, 
      tumor suppressor and anti-inflammatory pathways. These analyses have provided 
      useful research directions, but have been restricted to a limited number of 
      tissues, and have focused on individual genes, rather than whole-genome 
      transcriptional networks. Furthermore, CR is thought to oppose age-associated 
      gene expression patterns, but detailed statistical investigations of this 
      hypothesis have not been carried out. RESULTS: Systemic effects of CR and aging 
      were identified by examining transcriptional responses to CR in 17 mouse tissue 
      types, as well as responses to aging in 22 tissues. CR broadly induced the 
      expression of genes known to inhibit oxidative stress (e.g., Mt1, Mt2), 
      inflammation (e.g., Nfkbia, Timp3) and tumorigenesis (e.g., Txnip, Zbtb16). 
      Additionally, a network-based investigation revealed that CR regulates a large 
      co-expression module containing genes associated with the metabolism and splicing 
      of mRNA (e.g., Cpsf6, Sfpq, Sfrs18). The effects of aging were, to a considerable 
      degree, similar among groups of co-expressed genes. Age-related gene expression 
      patterns characteristic of most mouse tissues were identified, including up 
      regulation of granulin (Grn) and secreted phosphoprotein 1 (Spp1). The 
      transcriptional association between CR and aging varied at different levels of 
      analysis. With respect to gene subsets associated with certain biological 
      processes (e.g., immunity and inflammation), CR opposed age-associated expression 
      patterns. However, among all genes, global transcriptional effects of CR were 
      only weakly related to those of aging. CONCLUSION: The study of aging, and of 
      interventions thought to combat aging, has much to gain from data-driven and 
      unbiased genomic investigations. Expression patterns identified in this analysis 
      characterize a generalized response of mammalian cells to CR and/or aging. These 
      patterns may be of importance in determining effects of CR on overall lifespan, 
      or as factors that underlie age-related disease. The association between CR and 
      aging warrants further study, but most evidence indicates that CR does not induce 
      a genome-wide "reversal" of age-associated gene expression patterns.
FAU - Swindell, William R
AU  - Swindell WR
AD  - Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 
      48109-2200, USA. wswindel@umich.edu
LA  - eng
GR  - T32-AG000114/AG/NIA NIH HHS/United States
GR  - T32-AR007197/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20091207
PL  - England
TA  - BMC Genomics
JT  - BMC genomics
JID - 100965258
SB  - IM
MH  - Aging/*genetics
MH  - Animals
MH  - Animals, Laboratory
MH  - *Caloric Restriction
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation
MH  - Mice
MH  - Oligonucleotide Array Sequence Analysis
PMC - PMC2795771
EDAT- 2009/12/09 06:00
MHDA- 2010/01/19 06:00
PMCR- 2009/12/07
CRDT- 2009/12/09 06:00
PHST- 2009/02/25 00:00 [received]
PHST- 2009/12/07 00:00 [accepted]
PHST- 2009/12/09 06:00 [entrez]
PHST- 2009/12/09 06:00 [pubmed]
PHST- 2010/01/19 06:00 [medline]
PHST- 2009/12/07 00:00 [pmc-release]
AID - 1471-2164-10-585 [pii]
AID - 10.1186/1471-2164-10-585 [doi]
PST - epublish
SO  - BMC Genomics. 2009 Dec 7;10:585. doi: 10.1186/1471-2164-10-585.