Difference between revisions of "Elliehausen 2021 Exp Gerontol"
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|title=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 | |title=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 | ||
|info=Exp Gerontol 155:111579. [https://www.ncbi.nlm.nih.gov/pubmed/34601078 PMID: 34601078 Open Access] | |info=Exp Gerontol 155:111579. [https://www.ncbi.nlm.nih.gov/pubmed/34601078 PMID: 34601078 Open Access] | ||
|authors=Elliehausen | |authors=Elliehausen Chrisitian J, Minton Dennis M, Nichol Alexander D, Konopka Adam R | ||
|year=2021 | |year=2021 | ||
|journal=Exp Gerontol | |journal=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 ( | |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 (H<sub>2</sub>O<sub>2</sub>) 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 H<sub>2</sub>O<sub>2</sub> 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 | |keywords=Aging, Healthspan, Metformin, Mitochondria, mTOR | ||
|editor=[[Plangger M]] | |editor=[[Plangger M]] | ||
|mipnetlab=US WI Madison Konopka A | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration | |area=Respiration, Pharmacology;toxicology | ||
|instruments=Oxygraph-2k | |diseases=Aging;senescence, Other | ||
|organism=Guinea pig | |||
|tissues=Skeletal muscle | |||
|preparations=Permeabilized tissue | |||
|couplingstates=LEAK, OXPHOS, ET | |||
|pathways=N, S, NS, ROX | |||
|instruments=Oxygraph-2k, O2k-Fluorometer | |||
|additional=2022-09 | |additional=2022-09 | ||
}} | }} |
Latest revision as of 12:57, 19 September 2022
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 |
Β» 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. β’ Keywords: Aging, Healthspan, Metformin, Mitochondria, mTOR β’ Bioblast editor: Plangger M β’ 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