Dantas 2024 Abstract IOC163
| Dantas WS, Heintz EC, Zunica ERM, Dousay M, Davuluri G, Yu CS, Murphy MP, Axelrod CL, Kirwan JP (2024) Mito-Q supplementation reverses sarcopenic obesity in aged mice by restoring mitochondrial function and enhancing antioxidant response. Mitochondr Physiol Network 28.11. |
Link: IOC163
Dantas Wagner S, Heintz Elizabeth C, Zunica Elizabeth RM, Dousay Megan, Davuluri Gangarao, Yu Chak S, Murphy Michael P, Axelrod Christopher L, Kirwan John P (2024)
Event: IOC163
Sarcopenic obesity is a highly prevalent disease with poor survival and ineffective medical interventions. Mitochondrial dysfunction is purported to be central to the underlying pathogenesis and is thought to impair both organelle biogenesis and quality control. Obesity and aging are primary contributors to sarcopenic obesity, and both increase mitochondria-derived reactive oxygen species (mtROS). However, the mechanisms underlying sarcopenic obesity are incompletely understood.
To examine whether the novel mitochondria-specific antioxidant, mitoquinone mesylate (Mito-Q), improves mitochondrial function and restores muscle quality during sarcopenic obesity.
76-week-old male C57BL/6J mice were randomized by body weight to 12 weeks of low-fat (LFD) or high-fat diet (HFD) treatment. Following 4 weeks of diet, animals on the HFD were further randomized based on body weight to Mito-Q (400 ΞΌM in tap water) or vehicle (400 ΞΌM of triphenylphosphonium cation (dTPP) in tap water) for 8 weeks. Body composition (NMR), food and water intake, and muscle function (grip strength) were determined at 0, 4, and 12 weeks. At 12 weeks, skeletal muscle was harvested and evaluated for mitochondrial function (high-resolution respirometry).
Mito-Q decreased body weight and fat mass in HFD mice (~27% and 39% reduction, respectively, vs. HFD + dTPP, P<0.001). Mito-Q attenuated the loss of lean mass in aged HFD mice (~70% increase vs. HFD + dTPP, P<0.0001). Conversely, Mito-Q restored grip strength (~91% increase vs. HFD + dTPP, P<0.0001) and attenuated the reduction in exercise capacity in the aged HFD mice (~76% increase vs. HFD + dTPP, P<0.0001). Interestingly, Mito-Q reduced frailty in aged HFD mice (~76% reduction vs. HFD + dTPP, P<0.0001). Improvements in physical function and frailty in aged HFD + Mito-Q mice were mediated by restoration of NADH- and succinate-linked OXPHOS (P<0.0001 vs. HFD + dTPP) and greater reduced coenzyme Q9 (CoQ9H2) (P<0.0001 vs. HFD + dTPP).
Mito-Q, a mitochondrial-specific antioxidant, may mitigate the age-related decline in muscle mass and function through cellular bioenergetic adaptations that confer protection against sarcopenia and restoration of defects in OXPHOS and the antioxidant response.
β’ Bioblast editor: Plangger M
β’ O2k-Network Lab: US LA Baton Rouge Noland RC
Labels: MiParea: Respiration, Pharmacology;toxicology Pathology: Aging;senescence, Obesity
Organism: Mouse
Coupling state: OXPHOS
Pathway: N, S
HRR: Oxygraph-2k
Affiliations
- Pennington Biomedical Research Center, Baton Rouge, LA
- Mitochondrial Biology Unit, University of Cambridge, UK
