Elliehausen 2021 Exp Gerontol

Elliehausen CJ, Minton DM, Nichol AD, Konopka AR (2021) Skeletal muscle mitochondrial respiration in a model of age-related osteoarthritis is impaired after dietary rapamycin. https://doi.org/10.1016/j.exger.2021.111579

» Exp Gerontol 155:111579. PMID: 34601078 Open Access

Elliehausen Chrisitian J, Minton Dennis M, Nichol Alexander D, Konopka Adam R (2021) Exp Gerontol

Abstract: A decline in skeletal muscle mitochondrial function is associated with the loss of skeletal muscle size and function during knee osteoarthritis (OA). We have recently reported that 12-weeks of dietary rapamycin (Rap, 14 ppm), with or without metformin (Met, 1000 ppm), increased plasma glucose and OA severity in male Dunkin Hartley (DH) guinea pigs, a model of naturally occurring, age-related OA. The purpose of the current study was to determine if increased OA severity after dietary Rap and Rap+Met was accompanied by impaired skeletal muscle mitochondrial function. Mitochondrial respiration and hydrogen peroxide (H₂O₂) emissions were evaluated in permeabilized muscle fibers via high-resolution respirometry and fluorometry using either a saturating bolus or titration of ADP. Rap and Rap+Met decreased complex I (CI)-linked respiration and tended to increase ADP sensitivity, consistent with previous findings in patients with end-stage OA. The decrease in CI-linked respiration was accompanied with lower CI protein abundance. Rap and Rap+Met did not change mitochondrial H₂O₂ emissions. There were no differences between mitochondrial function in Rap versus Rap+Met suggesting that Rap was likely driving the change in mitochondrial function. This is the first inquiry into how lifespan extending treatments Rap and Rap+Met can influence skeletal muscle mitochondria in a model of age-related OA. Collectively, our data suggest that Rap with or without Met inhibits CI-linked capacity and increases ADP sensitivity in DH guinea pigs that have greater OA severity. • Keywords: Aging, Healthspan, Metformin, Mitochondria, mTOR • Bioblast editor: Plangger M • O2k-Network Lab: US WI Madison Konopka A

Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Aging;senescence, Other 

Organism: Guinea pig  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k, O2k-Fluorometer 

2022-09