PMID- 38535998
OWN - NLM
STAT- MEDLINE
DCOM- 20240408
LR  - 20240425
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 16
IP  - 6
DP  - 2024 Mar 25
TI  - Targeting mitochondrial dysfunction using methylene blue or mitoquinone to 
      improve skeletal aging.
PG  - 4948-4964
LID - 10.18632/aging.205147 [doi]
AB  - Methylene blue (MB) is a well-established antioxidant that has been shown to 
      improve mitochondrial function in both in vitro and in vivo settings. Mitoquinone 
      (MitoQ) is a selective antioxidant that specifically targets mitochondria and 
      effectively reduces the accumulation of reactive oxygen species. To investigate 
      the effect of long-term administration of MB on skeletal morphology, we 
      administered MB to aged (18 months old) female C57BL/J6 mice, as well as to adult 
      male and female mice with a genetically diverse background (UM-HET3). 
      Additionally, we used MitoQ as an alternative approach to target mitochondrial 
      oxidative stress during aging in adult female and male UM-HET3 mice. Although we 
      observed some beneficial effects of MB and MitoQ in vitro, the administration of 
      these compounds in vivo did not alter the progression of age-induced bone loss. 
      Specifically, treating 18-month-old female mice with MB for 6 or 12 months did 
      not have an effect on age-related bone loss. Similarly, long-term treatment with 
      MB from 7 to 22 months or with MitoQ from 4 to 22 months of age did not affect 
      the morphology of cortical bone at the mid-diaphysis of the femur, trabecular 
      bone at the distal-metaphysis of the femur, or trabecular bone at the lumbar 
      vertebra-5 in UM-HET3 mice. Based on our findings, it appears that long-term 
      treatment with MB or MitoQ alone, as a means to reduce skeletal oxidative stress, 
      is insufficient to inhibit age-associated bone loss. This supports the notion 
      that interventions solely with antioxidants may not provide adequate protection 
      against skeletal aging.
FAU - Poudel, Sher Bahadur
AU  - Poudel SB
AD  - Department of Molecular Pathobiology, David B. Kriser Dental Center, New York 
      University College of Dentistry, New York, NY 10010-4086, USA.
FAU - Frikha-Benayed, Dorra
AU  - Frikha-Benayed D
AD  - Department of Biomedical Engineering, City College of New York, New York, NY 
      10031, USA.
FAU - Ruff, Ryan R
AU  - Ruff RR
AD  - Department of Epidemiology and Health Promotion, David B. Kriser Dental Center, 
      New York University College of Dentistry, New York, NY 10010-4086, USA.
FAU - Yildirim, Gozde
AU  - Yildirim G
AD  - Department of Molecular Pathobiology, David B. Kriser Dental Center, New York 
      University College of Dentistry, New York, NY 10010-4086, USA.
FAU - Dixit, Manisha
AU  - Dixit M
AD  - Department of Molecular Pathobiology, David B. Kriser Dental Center, New York 
      University College of Dentistry, New York, NY 10010-4086, USA.
FAU - Korstanje, Ron
AU  - Korstanje R
AD  - Jackson Aging Center, Nathan Shock Center for Excellence in the Basic Biology of 
      Aging, The Jackson’s Laboratories, Aging Center, Bar Harbor, ME 04609, 
      USA.
FAU - Robinson, Laura
AU  - Robinson L
AD  - Jackson Aging Center, Nathan Shock Center for Excellence in the Basic Biology of 
      Aging, The Jackson’s Laboratories, Aging Center, Bar Harbor, ME 04609, 
      USA.
FAU - Miller, Richard A
AU  - Miller RA
AD  - Department of Pathology and Geriatrics Center, University of Michigan, Ann Arbor, 
      MI 48109, USA.
FAU - Harrison, David E
AU  - Harrison DE
AD  - The Jackson Laboratory, Bar Harbor, ME 04609, USA.
FAU - Strong, John R
AU  - Strong JR
AD  - Geriatric Research, Education and Clinical Center and Research Service, South 
      Texas Veterans Health Care System, San Antonio, TX 78229, USA.
AD  - Department of Pharmacology, Barshop Institute for Longevity and Aging Studies, 
      The University of Texas Health Science Center, San Antonio, TX 78229, USA.
FAU - Schaffler, Mitchell B
AU  - Schaffler MB
AD  - Department of Biomedical Engineering, City College of New York, New York, NY 
      10031, USA.
FAU - Yakar, Shoshana
AU  - Yakar S
AD  - Department of Molecular Pathobiology, David B. Kriser Dental Center, New York 
      University College of Dentistry, New York, NY 10010-4086, USA.
LA  - eng
GR  - P30 AG038070/AG/NIA NIH HHS/United States
GR  - S10 OD010751/OD/NIH HHS/United States
GR  - R01 AG056397/AG/NIA NIH HHS/United States
GR  - S10 OD026699/OD/NIH HHS/United States
GR  - U01 AG022308/AG/NIA NIH HHS/United States
GR  - U01 AG022303/AG/NIA NIH HHS/United States
GR  - P30 AG013319/AG/NIA NIH HHS/United States
PT  - Journal Article
DEP - 20240325
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 47BYS17IY0 (mitoquinone)
RN  - 0 (Antioxidants)
RN  - T42P99266K (Methylene Blue)
RN  - 0 (Organophosphorus Compounds)
RN  - 1339-63-5 (Ubiquinone)
SB  - IM
MH  - Male
MH  - Female
MH  - Mice
MH  - Animals
MH  - *Antioxidants/pharmacology
MH  - Methylene Blue/pharmacology
MH  - Mice, Inbred C57BL
MH  - Oxidative Stress
MH  - Aging
MH  - *Mitochondrial Diseases
MH  - *Organophosphorus Compounds
MH  - Ubiquinone/*analogs & derivatives
PMC - PMC11006499
OTO - NOTNLM
OT  - antioxidants
OT  - bone
OT  - methylene blue
OT  - micro-CT
OT  - mitoquinone
COIS- CONFLICTS OF INTEREST: The authors declare no conflicts of interest related to 
      this study.
EDAT- 2024/03/27 12:48
MHDA- 2024/04/08 06:43
PMCR- 2024/03/31
CRDT- 2024/03/27 10:13
PHST- 2023/06/28 00:00 [received]
PHST- 2023/09/27 00:00 [accepted]
PHST- 2024/04/08 06:43 [medline]
PHST- 2024/03/27 12:48 [pubmed]
PHST- 2024/03/27 10:13 [entrez]
PHST- 2024/03/31 00:00 [pmc-release]
AID - 205147 [pii]
AID - 10.18632/aging.205147 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2024 Mar 25;16(6):4948-4964. doi: 10.18632/aging.205147. Epub 
      2024 Mar 25.