PMID- 28556428
OWN - NLM
STAT- MEDLINE
DCOM- 20171201
LR  - 20221207
IS  - 1474-9726 (Electronic)
IS  - 1474-9718 (Print)
IS  - 1474-9718 (Linking)
VI  - 16
IP  - 4
DP  - 2017 Aug
TI  - Identification of tissue-specific transcriptional markers of caloric restriction 
      in the mouse and their use to evaluate caloric restriction mimetics.
PG  - 750-760
LID - 10.1111/acel.12608 [doi]
AB  - Caloric restriction (CR) without malnutrition has been shown to retard several 
      aspects of the aging process and to extend lifespan in different species. There 
      is strong interest in the identification of CR mimetics (CRMs), compounds that 
      mimic the beneficial effects of CR on lifespan and healthspan without restriction 
      of energy intake. Identification of CRMs in mammals is currently inefficient due 
      to the lack of screening tools. We have performed whole-genome transcriptional 
      profiling of CR in seven mouse strains (C3H/HeJ, CBA/J, DBA/2J, B6C3F1/J, 
      129S1/SvImJ, C57BL/6J, and BALB/cJ) in white adipose tissue (WAT), gastrocnemius 
      muscle, heart, and brain neocortex. This analysis has identified tissue-specific 
      panels of genes that change in expression in multiple mouse strains with CR. We 
      validated a subset of genes with qPCR and used these to evaluate the potential 
      CRMs bezafibrate, pioglitazone, metformin, resveratrol, quercetin, 
      2,4-dinitrophenol, and L-carnitine when fed to C57BL/6J 2-month-old mice for 
      3 months. Compounds were also evaluated for their ability to modulate previously 
      characterized biomarkers of CR, including mitochondrial enzymes citrate synthase 
      and SIRT3, plasma inflammatory cytokines TNF-alpha and IFN-gamma, glycated hemoglobin 
      (HbA1c) levels and adipocyte size. Pioglitazone, a PPAR-gamma agonist, and 
      L-carnitine, an amino acid involved in lipid metabolism, displayed the strongest 
      effects on both the novel transcriptional markers of CR and the additional CR 
      biomarkers tested. Our findings provide panels of tissue-specific transcriptional 
      markers of CR that can be used to identify novel CRMs, and also represent the 
      first comparative molecular analysis of several potential CRMs in multiple 
      tissues in mammals.
CI  - (c) 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley 
      & Sons Ltd.
FAU - Barger, Jamie L
AU  - Barger JL
AUID- ORCID: 0000-0001-8694-0068
AD  - LifeGen Technologies LLC, Madison, WI, USA.
FAU - Vann, James M
AU  - Vann JM
AD  - LifeGen Technologies LLC, Madison, WI, USA.
FAU - Cray, Nicole L
AU  - Cray NL
AD  - LifeGen Technologies LLC, Madison, WI, USA.
FAU - Pugh, Thomas D
AU  - Pugh TD
AD  - LifeGen Technologies LLC, Madison, WI, USA.
FAU - Mastaloudis, Angela
AU  - Mastaloudis A
AD  - Center for Anti-Aging Research, NSE Products, Inc., Provo, UT, USA.
FAU - Hester, Shelly N
AU  - Hester SN
AD  - Center for Anti-Aging Research, NSE Products, Inc., Provo, UT, USA.
FAU - Wood, Steven M
AU  - Wood SM
AD  - Center for Anti-Aging Research, NSE Products, Inc., Provo, UT, USA.
FAU - Newton, Michael A
AU  - Newton MA
AD  - Departments of Statistics and of Biostatistics and Medical Informatics, 
      University of Wisconsin, Madison, WI, USA.
FAU - Weindruch, Richard
AU  - Weindruch R
AD  - LifeGen Technologies LLC, Madison, WI, USA.
AD  - Department of Medicine, SMPH, University of Wisconsin, Madison, WI, USA.
AD  - Geriatric Research, Education and Clinical Center, William S. Middleton Memorial 
      Veterans Hospital, Madison, WI, USA.
FAU - Prolla, Tomas A
AU  - Prolla TA
AD  - LifeGen Technologies LLC, Madison, WI, USA.
AD  - Departments of Genetics and Medical Genetics, University of Wisconsin, Madison, 
      WI, USA.
LA  - eng
GR  - U54 AI117924/AI/NIAID NIH HHS/United States
GR  - R43 AG034833/AG/NIA NIH HHS/United States
GR  - R01 AG038679/AG/NIA NIH HHS/United States
PT  - Journal Article
DEP - 20170526
PL  - England
TA  - Aging Cell
JT  - Aging cell
JID - 101130839
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Sirt3 protein, mouse)
RN  - 0 (Stilbenes)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9100L32L2N (Metformin)
RN  - 9IKM0I5T1E (Quercetin)
RN  - EC 2.3.3.1 (Citrate (si)-Synthase)
RN  - EC 3.5.1.- (Sirtuin 3)
RN  - Q13SKS21MN (2,4-Dinitrophenol)
RN  - Q369O8926L (Resveratrol)
RN  - S7UI8SM58A (Carnitine)
RN  - X4OV71U42S (Pioglitazone)
RN  - Y9449Q51XH (Bezafibrate)
SB  - IM
MH  - 2,4-Dinitrophenol/pharmacology
MH  - Adipose Tissue, White/drug effects/metabolism
MH  - Aging/*drug effects/metabolism
MH  - Animals
MH  - Bezafibrate/pharmacology
MH  - *Caloric Restriction
MH  - Carnitine/*pharmacology
MH  - Citrate (si)-Synthase/genetics/metabolism
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation/*drug effects
MH  - Glycated Hemoglobin/genetics/metabolism
MH  - Interferon-gamma/genetics/metabolism
MH  - Male
MH  - Metformin/pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred CBA
MH  - Mice, Inbred DBA
MH  - Mice, Inbred Strains
MH  - Muscle, Skeletal/drug effects/metabolism
MH  - Myocardium/metabolism
MH  - Neocortex/drug effects/metabolism
MH  - Pioglitazone
MH  - Quercetin/pharmacology
MH  - Resveratrol
MH  - Sirtuin 3/genetics/metabolism
MH  - Stilbenes/pharmacology
MH  - Thiazolidinediones/*pharmacology
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
PMC - PMC5506434
OTO - NOTNLM
OT  - aging
OT  - biomarkers
OT  - caloric restriction
OT  - gene expression
OT  - mouse
EDAT- 2017/05/31 06:00
MHDA- 2017/12/02 06:00
PMCR- 2017/08/01
CRDT- 2017/05/31 06:00
PHST- 2017/03/28 00:00 [accepted]
PHST- 2017/05/31 06:00 [pubmed]
PHST- 2017/12/02 06:00 [medline]
PHST- 2017/05/31 06:00 [entrez]
PHST- 2017/08/01 00:00 [pmc-release]
AID - ACEL12608 [pii]
AID - 10.1111/acel.12608 [doi]
PST - ppublish
SO  - Aging Cell. 2017 Aug;16(4):750-760. doi: 10.1111/acel.12608. Epub 2017 May 26.