PMID- 17381838
OWN - NLM
STAT- MEDLINE
DCOM- 20070525
LR  - 20181113
IS  - 1471-2164 (Electronic)
IS  - 1471-2164 (Linking)
VI  - 8
DP  - 2007 Mar 23
TI  - Gene expression profiling of aging reveals activation of a p53-mediated 
      transcriptional program.
PG  - 80
AB  - BACKGROUND: Aging has been associated with widespread changes at the gene 
      expression level in multiple mammalian tissues. We have used high density 
      oligonucleotide arrays and novel statistical methods to identify specific 
      transcriptional classes that may uncover biological processes that play a central 
      role in mammalian aging. RESULTS: We identified 712 transcripts that are 
      differentially expressed in young (5 month old) and old (25-month old) mouse 
      skeletal muscle. Caloric restriction (CR) completely or partially reversed 87% of 
      the changes in expression. Examination of individual genes revealed a 
      transcriptional profile indicative of increased p53 activity in the older muscle. 
      To determine whether the increase in p53 activity is associated with 
      transcriptional activation of apoptotic targets, we performed RT-PCR on four well 
      known mediators of p53-induced apoptosis: puma, noxa, tnfrsf10b and bok. 
      Expression levels for these proapoptotic genes increased significantly with age 
      (P < 0.05), while CR significantly lowered expression levels for these genes as 
      compared to control fed old mice (P < 0.05). Age-related induction of p53-related 
      genes was observed in multiple tissues, but was not observed in young SOD2+/- and 
      GPX4+/- mice, suggesting that oxidative stress does not induce the expression of 
      these genes. Western blot analysis confirmed that protein levels for both p21 and 
      GADD45a, two established transcriptional targets of p53, were higher in the older 
      muscle tissue. CONCLUSION: These observations support a role for p53-mediated 
      transcriptional program in mammalian aging and suggest that mechanisms other than 
      reactive oxygen species are involved in the age-related transcriptional 
      activation of p53 targets.
FAU - Edwards, Michael G
AU  - Edwards MG
AD  - Department of Genetics and Medical Genetics, University of Wisconsin, Madison, 
      WI, USA. medward71@yahoo.com <medward71@yahoo.com>
FAU - Anderson, Rozalyn M
AU  - Anderson RM
FAU - Yuan, Ming
AU  - Yuan M
FAU - Kendziorski, Christina M
AU  - Kendziorski CM
FAU - Weindruch, Richard
AU  - Weindruch R
FAU - Prolla, Tomas A
AU  - Prolla TA
LA  - eng
GR  - T32 AG000213/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070323
PL  - England
TA  - BMC Genomics
JT  - BMC genomics
JID - 100965258
RN  - 0 (DNA, Complementary)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 9002-62-4 (Prolactin)
SB  - IM
MH  - Aging/*genetics
MH  - Animals
MH  - Cloning, Molecular
MH  - DNA, Complementary
MH  - Embryonic Development
MH  - Female
MH  - *Gene Expression Profiling
MH  - Goats
MH  - Placenta/*physiology
MH  - Pregnancy
MH  - Prolactin/*analogs & derivatives/genetics/*physiology
MH  - RNA, Messenger/genetics
MH  - Recombinant Proteins/metabolism
MH  - *Transcription, Genetic
MH  - Tumor Suppressor Protein p53/*genetics
PMC - PMC1847444
EDAT- 2007/03/27 09:00
MHDA- 2007/05/26 09:00
PMCR- 2007/03/23
CRDT- 2007/03/27 09:00
PHST- 2006/09/28 00:00 [received]
PHST- 2007/03/23 00:00 [accepted]
PHST- 2007/03/27 09:00 [pubmed]
PHST- 2007/05/26 09:00 [medline]
PHST- 2007/03/27 09:00 [entrez]
PHST- 2007/03/23 00:00 [pmc-release]
AID - 1471-2164-8-80 [pii]
AID - 10.1186/1471-2164-8-80 [doi]
PST - epublish
SO  - BMC Genomics. 2007 Mar 23;8:80. doi: 10.1186/1471-2164-8-80.