Thompson 2023 Geroscience

Thompson SD, Barrett KL, Rugel CL, Redmond R, Rudofski A, Kurian J, Curtin JL, Dayanidhi S, Lavasani M (2023) Sex-specific preservation of neuromuscular function and metabolism following systemic transplantation of multipotent adult stem cells in a murine model of progeria. https://doi.org/10.1007/s11357-023-00892-5

» Geroscience [Epub ahead of print]. PMID: 37535205 Open Access

Thompson Seth D, Barrett Kelsey L, Rugel Chelsea L, Redmond Robin, Rudofski Alexia, Kurian Jacob, Curtin Jodi L, Dayanidhi Sudarshan, Lavasani Mitra (2023) Geroscience

Abstract: Onset and rates of sarcopenia, a disease characterized by a loss of muscle mass and function with age, vary greatly between sexes. Currently, no clinical interventions successfully arrest age-related muscle impairments since the decline is frequently multifactorial. Previously, we found that systemic transplantation of our unique adult multipotent muscle-derived stem/progenitor cells (MDSPCs) isolated from young mice-but not old-extends the health-span in DNA damage mouse models of progeria, a disease of accelerated aging. Additionally, induced neovascularization in the muscles and brain-where no transplanted cells were detected-strongly suggests a systemic therapeutic mechanism, possibly activated through circulating secreted factors. Herein, we used ZMPSTE24-deficient mice, a lamin A defect progeria model, to investigate the ability of young MDSPCs to preserve neuromuscular tissue structure and function. We show that progeroid ZMPST24-deficient mice faithfully exhibit sarcopenia and age-related metabolic dysfunction. However, systemic transplantation of young MDSPCs into ZMPSTE24-deficient progeroid mice sustained healthy function and histopathology of muscular tissues throughout their 6-month life span in a sex-specific manner. Indeed, female-but not male-mice systemically transplanted with young MDSPCs demonstrated significant preservation of muscle endurance, muscle fiber size, mitochondrial respirometry, and neuromuscular junction morphometrics. These novel findings strongly suggest that young MDSPCs modulate the systemic environment of aged animals by secreted rejuvenating factors to maintain a healthy homeostasis in a sex-specific manner and that the female muscle microenvironment remains responsive to exogenous regenerative cues in older age. This work highlights the age- and sex-related differences in neuromuscular tissue degeneration and the future prospect of preserving health in older adults with systemic regenerative treatments. • Keywords: Aging, Cell therapy, Metabolism, Muscle fatigue, Neuromuscular tissues, Progeria, Regeneration, Sex differences, Skeletal muscle • Bioblast editor: Plangger M • O2k-Network Lab: US IL Chicago Dayanidhi S

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

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

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

2023-08