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Research Paper|Volume 16, Issue 6|pp 4948—4964

Targeting mitochondrial dysfunction using methylene blue or mitoquinone to improve skeletal aging

Sher Bahadur Poudel1, Dorra Frikha-Benayed2, Ryan R. Ruff3, Gozde Yildirim1, Manisha Dixit1, Ron Korstanje4, Laura Robinson4, Richard A. Miller5, David E. Harrison6, John R. Strong7,8, Mitchell B. Schaffler2, Shoshana Yakar1
  • 1Department of Molecular Pathobiology, David B. Kriser Dental Center, New York University College of Dentistry, New York, NY 10010-4086, USA
  • 2Department of Biomedical Engineering, City College of New York, New York, NY 10031, USA
  • 3Department of Epidemiology and Health Promotion, David B. Kriser Dental Center, New York University College of Dentistry, New York, NY 10010-4086, USA
  • 4Jackson Aging Center, Nathan Shock Center for Excellence in the Basic Biology of Aging, The Jackson’s Laboratories, Aging Center, Bar Harbor, ME 04609, USA
  • 5Department of Pathology and Geriatrics Center, University of Michigan, Ann Arbor, MI 48109, USA
  • 6The Jackson Laboratory, Bar Harbor, ME 04609, USA
  • 7Geriatric Research, Education and Clinical Center and Research Service, South Texas Veterans Health Care System, San Antonio, TX 78229, USA
  • 8Department of Pharmacology, Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center, San Antonio, TX 78229, USA
Received: June 28, 2023Accepted: September 27, 2023Published: March 25, 2024
https://doi.org/10.18632/aging.205147

Copyright: © 2024 Poudel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.