Bhaskaran 2020 Aging Cell

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Publications in the MiPMap
Bhaskaran S, Pollock N, C Macpherson P, Ahn B, Piekarz KM, Staunton CA, Brown JL, Qaisar R, Vasilaki A, Richardson A, McArdle A, Jackson MJ, Brooks SV, Van Remmen H (2020) Neuron-specific deletion of CuZnSOD leads to an advanced sarcopenic phenotype in older mice. Aging Cell 19:e13225.

» PMID: 32886862 Open Access

Bhaskaran Shylesh, Pollock Natalie, Macpherson Peter C, Ahn Bumsoo, Piekarz Katarzyna M, Staunton Caroline A, Brown Jacob L, Qaisar Rizwan, Vasilaki Aphrodite, Richardson Arlan, McArdle Anne, Jackson Malcolm J, Brooks Susan V, Van Remmen Holly (2020) Aging Cell

Abstract: Age-associated loss of muscle mass and function (sarcopenia) has a profound effect on the quality of life in the elderly. Our previous studies show that CuZnSOD deletion in mice (Sod1-/- mice) recapitulates sarcopenia phenotypes, including elevated oxidative stress and accelerated muscle atrophy, weakness, and disruption of neuromuscular junctions (NMJs). To determine whether deletion of Sod1 initiated in neurons in adult mice is sufficient to induce muscle atrophy, we treated young (2- to 4-month-old) Sod1flox/SlickHCre mice with tamoxifen to generate i-mn-Sod1KO mice. CuZnSOD protein was 40-50% lower in neuronal tissue in i-mn-Sod1KO mice. Motor neuron number in ventral spinal cord was reduced 28% at 10 months and more than 50% in 18- to 22-month-old i-mn-Sod1KO mice. By 24 months, 22% of NMJs in i-mn-Sod1KO mice displayed a complete lack of innervation and deficits in specific force that are partially reversed by direct muscle stimulation, supporting the loss of NMJ structure and function. Muscle mass was significantly reduced by 16 months of age and further decreased at 24 months of age. Overall, our findings show that neuronal-specific deletion of CuZnSOD is sufficient to cause motor neuron loss in young mice, but that NMJ disruption, muscle atrophy, and weakness are not evident until past middle age. These results suggest that loss of innervation is critical but may not be sufficient until the muscle reaches a threshold beyond which it cannot compensate for neuronal loss or rescue additional fibers past the maximum size of the motor unit. Keywords: CuZnSOD, Aging, Denervation, Motor neuron, Sarcopenia Bioblast editor: Plangger M O2k-Network Lab: US OK Oklahoma City Van Remmen H


Labels: MiParea: Respiration, Genetic knockout;overexpression  Pathology: Aging;senescence 

Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 


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

2020-09