PMID- 26009878
OWN - NLM
STAT- MEDLINE
DCOM- 20160408
LR  - 20220310
IS  - 1474-9726 (Electronic)
IS  - 1474-9718 (Print)
IS  - 1474-9718 (Linking)
VI  - 14
IP  - 4
DP  - 2015 Aug
TI  - Increases of M2a macrophages and fibrosis in aging muscle are influenced by bone 
      marrow aging and negatively regulated by muscle-derived nitric oxide.
PG  - 678-88
LID - 10.1111/acel.12350 [doi]
AB  - Muscle aging is associated with changes in myeloid cell phenotype that may 
      influence age-related changes in muscle structure. We tested whether preventing 
      age-related reductions in muscle neuronal nitric oxide synthase (nNOS) would 
      obviate age-related changes in myeloid cells in muscle. Our findings show that 
      muscle aging is associated with elevations of anti-inflammatory M2a macrophages 
      that can increase muscle fibrosis. Expression of a muscle-specific nNOS transgene 
      in mice prevented age-related increases in M2a macrophages. Transgene expression 
      also reduced expression of collagens and decreased muscle fibrosis. The nNOS 
      transgene prevented age-related increases in arginase-1 but did not influence 
      TGFbeta expression, indicating that the transgene may prevent age-related muscle 
      fibrosis by inhibiting the arginase-dependent profibrotic pathway. Although aged 
      satellite cells or fibro-adipogenic precursor (FAPs) cells also promote fibrosis, 
      transgene expression had no effect on the expression of key signaling molecules 
      that regulate fibrogenic activity of those cells. Finally, we tested whether 
      increases in M2a macrophages and the associated increase in fibrosis were 
      attributable to aging of myeloid lineage cells. Young bone marrow cells (BMCs) 
      were transplanted into young or old mice, and muscles were collected 8 months 
      later. Muscles of young mice receiving young BMCs showed no effect on M2a 
      macrophage number or collagen accumulation compared to age-matched, 
      nontransplanted controls. However, muscles of old mice receiving young BMCs 
      showed fewer M2a macrophages and less accumulation of collagen. Thus, the 
      age-related increase in M2a macrophages in aging muscle and the associated muscle 
      fibrosis are determined in part by the age of bone marrow cells.
CI  - (c) 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley 
      & Sons Ltd.
FAU - Wang, Ying
AU  - Wang Y
AD  - Molecular, Cellular & Integrative Physiology Program, University of California, 
      Los Angeles, CA, 90095, USA.
FAU - Wehling-Henricks, Michelle
AU  - Wehling-Henricks M
AD  - Department of Integrative Biology and Physiology, University of California, Los 
      Angeles, CA, 90095, USA.
FAU - Samengo, Giuseppina
AU  - Samengo G
AD  - Department of Integrative Biology and Physiology, University of California, Los 
      Angeles, CA, 90095, USA.
FAU - Tidball, James G
AU  - Tidball JG
AD  - Molecular, Cellular & Integrative Physiology Program, University of California, 
      Los Angeles, CA, 90095, USA.
AD  - Department of Integrative Biology and Physiology, University of California, Los 
      Angeles, CA, 90095, USA.
AD  - Department of Pathology and Laboratory Medicine, David Geffen School of Medicine 
      at UCLA, University of California, Los Angeles, CA, 90095, USA.
LA  - eng
GR  - R01 AG041147/AG/NIA NIH HHS/United States
GR  - R01 AR054451/AR/NIAMS NIH HHS/United States
GR  - R01AR054451/AR/NIAMS NIH HHS/United States
GR  - R01AG041147/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150525
PL  - England
TA  - Aging Cell
JT  - Aging cell
JID - 101130839
RN  - 0 (Transforming Growth Factor beta)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 9007-34-5 (Collagen)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 1.14.13.39 (Nos1 protein, mouse)
RN  - EC 3.5.3.1 (Arg1 protein, mouse)
RN  - EC 3.5.3.1 (Arginase)
SB  - IM
MH  - Aging/genetics/*pathology
MH  - Animals
MH  - Arginase/genetics/metabolism
MH  - Bone Marrow Cells/metabolism/pathology
MH  - Cell Count
MH  - Collagen/genetics/metabolism
MH  - Female
MH  - Fibrosis
MH  - Gene Expression Regulation, Developmental
MH  - Humans
MH  - Macrophages/metabolism/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Muscle, Skeletal/metabolism/*pathology
MH  - Neurons/metabolism/pathology
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Synthase Type I/genetics/*metabolism
MH  - Satellite Cells, Skeletal Muscle/metabolism/pathology
MH  - Transforming Growth Factor beta/genetics/metabolism
MH  - Transgenes
PMC - PMC4531081
OTO - NOTNLM
OT  - aging
OT  - fibrosis
OT  - inflammation
OT  - macrophage
OT  - mouse
OT  - nitric oxide synthase
OT  - skeletal muscle
EDAT- 2015/05/27 06:00
MHDA- 2016/04/09 06:00
PMCR- 2015/08/01
CRDT- 2015/05/27 06:00
PHST- 2015/04/05 00:00 [accepted]
PHST- 2015/05/27 06:00 [entrez]
PHST- 2015/05/27 06:00 [pubmed]
PHST- 2016/04/09 06:00 [medline]
PHST- 2015/08/01 00:00 [pmc-release]
AID - 10.1111/acel.12350 [doi]
PST - ppublish
SO  - Aging Cell. 2015 Aug;14(4):678-88. doi: 10.1111/acel.12350. Epub 2015 May 25.