PMID- 25456069
OWN - NLM
STAT- MEDLINE
DCOM- 20150324
LR  - 20211203
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 156
IP  - 2
DP  - 2015 Feb
TI  - Regulation of mTOR activity in Snell dwarf and GH receptor gene-disrupted mice.
PG  - 565-75
LID - 10.1210/en.2014-1690 [doi]
AB  - The involvement of mammalian target of rapamycin (mTOR) in lifespan control in 
      invertebrates, calorie-restricted rodents, and extension of mouse lifespan by 
      rapamycin have prompted speculation that diminished mTOR function may contribute 
      to mammalian longevity in several settings. We show here that mTOR complex-1 
      (mTORC1) activity is indeed lower in liver, muscle, heart, and kidney tissue of 
      Snell dwarf and global GH receptor (GHR) gene-disrupted mice (GHR-/-), consistent 
      with previous studies. Surprisingly, activity of mTORC2 is higher in fasted Snell 
      and GHR-/- than in littermate controls in all 4 tissues tested. Resupply of food 
      enhanced mTORC1 activity in both controls and long-lived mutant mice but 
      diminished mTORC2 activity only in the long-lived mice. Mice in which GHR has 
      been disrupted only in the liver do not show extended lifespan and also fail to 
      show the decline in mTORC1 and increase in mTORC2 seen in mice with global loss 
      of GHR. The data suggest that the antiaging effects in the Snell dwarf and GHR-/- 
      mice are accompanied by both a decline in mTORC1 in multiple organs and an 
      increase in fasting levels of mTORC2. Neither the lifespan nor mTOR effects 
      appear to be mediated by direct GH effects on liver or by the decline in plasma 
      IGF-I, a shared trait in both global and liver-specific GHR-/- mice. Our data 
      suggest that a more complex pattern of hormonal effects and intertissue 
      interactions may be responsible for regulating both lifespan and mTORC2 function 
      in these mouse models of delayed aging.
FAU - Dominick, Graham
AU  - Dominick G
AD  - Department of Molecular, Cellular, and Developmental Biology (G.D.), University 
      of Michigan College of Literature, Science and the Arts, Ann Arbor, Michigan 
      48109; Edison Biotechnology Institute (D.E.B., E.O.L., J.J.K.), Ohio University, 
      Athens, Ohio 45701; Department of Pathology (X.L., R.A.M., G.G.G.), University of 
      Michigan School of Medicine Ann Arbor, Michigan 48109; and University of Michigan 
      Geriatrics Center (R.A.M.), Ann Arbor, Michigan 48109.
FAU - Berryman, Darlene E
AU  - Berryman DE
FAU - List, Edward O
AU  - List EO
FAU - Kopchick, John J
AU  - Kopchick JJ
FAU - Li, Xinna
AU  - Li X
FAU - Miller, Richard A
AU  - Miller RA
FAU - Garcia, Gonzalo G
AU  - Garcia GG
LA  - eng
GR  - R01 AG019899/AG/NIA NIH HHS/United States
GR  - P30 AG024824/AG/NIA NIH HHS/United States
GR  - AG031736/AG/NIA NIH HHS/United States
GR  - AG019899/AG/NIA NIH HHS/United States
GR  - P30 AG013283/AG/NIA NIH HHS/United States
GR  - P01 AG031736/AG/NIA NIH HHS/United States
GR  - AG013283/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20141202
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Receptors, Somatotropin)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Dwarfism, Pituitary/*metabolism
MH  - Fasting/*physiology
MH  - Female
MH  - Liver/metabolism
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mechanistic Target of Rapamycin Complex 2
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Multiprotein Complexes/*metabolism
MH  - Receptors, Somatotropin/*metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC4298324
EDAT- 2014/12/03 06:00
MHDA- 2015/03/25 06:00
PMCR- 2016/02/01
CRDT- 2014/12/03 06:00
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/03/25 06:00 [medline]
PHST- 2016/02/01 00:00 [pmc-release]
AID - EN-14-1690 [pii]
AID - 10.1210/en.2014-1690 [doi]
PST - ppublish
SO  - Endocrinology. 2015 Feb;156(2):565-75. doi: 10.1210/en.2014-1690. Epub 2014 Dec 
      2.