PMID- 31953150
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20210618
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Print)
IS  - 0891-5849 (Linking)
VI  - 152
DP  - 2020 May 20
TI  - Deletion of Nrf2 shortens lifespan in C57BL6/J male mice but does not alter the 
      health and survival benefits of caloric restriction.
PG  - 650-658
LID - S0891-5849(19)32365-2 [pii]
LID - 10.1016/j.freeradbiomed.2020.01.005 [doi]
AB  - Caloric restriction (CR) is the leading non-pharmaceutical dietary intervention 
      to improve health- and lifespan in most model organisms. A wide array of cellular 
      pathways is induced in response to CR and CR-mimetics, including the 
      transcriptional activator Nuclear factor erythroid-2-related factor 2 (Nrf2), 
      which is essential in the upregulation of multiple stress-responsive and 
      mitochondrial enzymes. Nrf2 is necessary in tumor protection but is not essential 
      for the lifespan extending properties of CR in outbred mice. Here, we sought to 
      study Nrf2-knockout (KO) mice and littermate controls in male C57BL6/J, an inbred 
      mouse strain. Deletion of Nrf2 resulted in shortened lifespan compared to 
      littermate controls only under ad libitum conditions. CR-mediated lifespan 
      extension and physical performance improvements did not require Nrf2. Metabolic 
      and protein homeostasis and activation of tissue-specific cytoprotective proteins 
      were dependent on Nrf2 expression. These results highlight an important 
      contribution of Nrf2 for normal lifespan and stress response.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Pomatto, Laura C D
AU  - Pomatto LCD
AD  - Translational Gerontology Branch, National Institute on Aging, National Institute 
      of Health, Baltimore, MD, 21224, USA; National Institute on General Medical 
      Sciences, National Institute of Health, Bethesda, MD, 20892, USA.
FAU - Dill, Theresa
AU  - Dill T
AD  - Translational Gerontology Branch, National Institute on Aging, National Institute 
      of Health, Baltimore, MD, 21224, USA.
FAU - Carboneau, Bethany
AU  - Carboneau B
AD  - Translational Gerontology Branch, National Institute on Aging, National Institute 
      of Health, Baltimore, MD, 21224, USA.
FAU - Levan, Sophia
AU  - Levan S
AD  - Translational Gerontology Branch, National Institute on Aging, National Institute 
      of Health, Baltimore, MD, 21224, USA.
FAU - Kato, Jonathan
AU  - Kato J
AD  - Translational Gerontology Branch, National Institute on Aging, National Institute 
      of Health, Baltimore, MD, 21224, USA.
FAU - Mercken, Evi M
AU  - Mercken EM
AD  - Translational Gerontology Branch, National Institute on Aging, National Institute 
      of Health, Baltimore, MD, 21224, USA.
FAU - Pearson, Kevin J
AU  - Pearson KJ
AD  - Translational Gerontology Branch, National Institute on Aging, National Institute 
      of Health, Baltimore, MD, 21224, USA.
FAU - Bernier, Michel
AU  - Bernier M
AD  - Translational Gerontology Branch, National Institute on Aging, National Institute 
      of Health, Baltimore, MD, 21224, USA.
FAU - de Cabo, Rafael
AU  - de Cabo R
AD  - Translational Gerontology Branch, National Institute on Aging, National Institute 
      of Health, Baltimore, MD, 21224, USA. Electronic address: decaboRa@mail.nih.gov.
LA  - eng
GR  - Z01 AG000362/ImNIH/Intramural NIH HHS/United States
GR  - Z01 AG000368/ImNIH/Intramural NIH HHS/United States
GR  - ZIA AG000361/ImNIH/Intramural NIH HHS/United States
GR  - FI2 GM123963/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20200115
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - Animals
MH  - *Caloric Restriction
MH  - *Longevity/genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NF-E2-Related Factor 2/genetics
PMC - PMC7382945
MID - NIHMS1551533
COIS- Declaration of competing interest None to declare.
EDAT- 2020/01/19 06:00
MHDA- 2021/06/22 06:00
PMCR- 2021/05/20
CRDT- 2020/01/19 06:00
PHST- 2019/11/21 00:00 [received]
PHST- 2020/01/02 00:00 [revised]
PHST- 2020/01/05 00:00 [accepted]
PHST- 2020/01/19 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/01/19 06:00 [entrez]
PHST- 2021/05/20 00:00 [pmc-release]
AID - S0891-5849(19)32365-2 [pii]
AID - 10.1016/j.freeradbiomed.2020.01.005 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2020 May 20;152:650-658. doi: 
      10.1016/j.freeradbiomed.2020.01.005. Epub 2020 Jan 15.