PMID- 18287083
OWN - NLM
STAT- MEDLINE
DCOM- 20080313
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 105
IP  - 7
DP  - 2008 Feb 19
TI  - Nrf2 mediates cancer protection but not prolongevity induced by caloric 
      restriction.
PG  - 2325-30
LID - 10.1073/pnas.0712162105 [doi]
AB  - Caloric restriction (CR) is the most potent intervention known to both protect 
      against carcinogenesis and extend lifespan in laboratory animals. A variety of 
      anticarcinogens and CR mimetics induce and activate the NF-E2-related factor 2 
      (Nrf2) pathway. Nrf2, in turn, induces a number of antioxidative and 
      carcinogen-detoxifying enzymes. Thus, Nrf2 offers a promising target for 
      anticarcinogenesis and antiaging interventions. We used Nrf2-disrupted (KO) mice 
      to examine its role on the biological effects of CR. Here, we show that Nrf2 is 
      responsible for most of the anticarcinogenic effects of CR, but is dispensable 
      for increased insulin sensitivity and lifespan extension. Nrf2-deficient mice 
      developed tumors more readily in response to carcinogen exposure than did WT 
      mice, and CR was ineffective in suppressing tumors in the KO mice. However, CR 
      extended lifespan and increased insulin sensitivity similarly in KO and WT mice. 
      These findings identify a molecular pathway that dissociates the prolongevity and 
      anticarcinogenic effects of CR.
FAU - Pearson, Kevin J
AU  - Pearson KJ
AD  - Laboratories of Experimental Gerontology, Clinical Investigation, and Immunology 
      and Research Resources Branch, National Institute on Aging, National Institutes 
      of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
FAU - Lewis, Kaitlyn N
AU  - Lewis KN
FAU - Price, Nathan L
AU  - Price NL
FAU - Chang, Joy W
AU  - Chang JW
FAU - Perez, Evelyn
AU  - Perez E
FAU - Cascajo, Maria Victoria
AU  - Cascajo MV
FAU - Tamashiro, Kellie L
AU  - Tamashiro KL
FAU - Poosala, Suresh
AU  - Poosala S
FAU - Csiszar, Anna
AU  - Csiszar A
FAU - Ungvari, Zoltan
AU  - Ungvari Z
FAU - Kensler, Thomas W
AU  - Kensler TW
FAU - Yamamoto, Masayuki
AU  - Yamamoto M
FAU - Egan, Josephine M
AU  - Egan JM
FAU - Longo, Dan L
AU  - Longo DL
FAU - Ingram, Donald K
AU  - Ingram DK
FAU - Navas, Placido
AU  - Navas P
FAU - de Cabo, Rafael
AU  - de Cabo R
LA  - eng
GR  - R00 HD055030/HD/NICHD NIH HHS/United States
GR  - HD055030/HD/NICHD NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
GR  - R01 DK077623/DK/NIDDK NIH HHS/United States
GR  - K99 HD055030/HD/NICHD NIH HHS/United States
GR  - DK077623/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080219
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Insulin)
RN  - 0 (NF-E2-Related Factor 2)
RN  - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone))
RN  - EC 1.6.5.2 (Nqo1 protein, mouse)
RN  - EC 1.6.99.1 (NADPH Dehydrogenase)
SB  - IM
MH  - Animals
MH  - *Caloric Restriction
MH  - Gene Expression Regulation
MH  - Insulin/metabolism
MH  - Longevity/physiology
MH  - Mice
MH  - Mice, Knockout
MH  - NAD(P)H Dehydrogenase (Quinone)
MH  - NADPH Dehydrogenase/genetics/metabolism
MH  - NF-E2-Related Factor 2/deficiency/genetics/*metabolism
MH  - Neoplasms/genetics/*metabolism/*prevention & control
MH  - Sensitivity and Specificity
MH  - Survival Rate
PMC - PMC2268135
COIS- The authors declare no conflict of interest.
EDAT- 2008/02/22 09:00
MHDA- 2008/03/14 09:00
PMCR- 2008/02/19
CRDT- 2008/02/22 09:00
PHST- 2008/02/22 09:00 [pubmed]
PHST- 2008/03/14 09:00 [medline]
PHST- 2008/02/22 09:00 [entrez]
PHST- 2008/02/19 00:00 [pmc-release]
AID - 0712162105 [pii]
AID - 9388 [pii]
AID - 10.1073/pnas.0712162105 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2325-30. doi: 
      10.1073/pnas.0712162105. Epub 2008 Feb 19.