Molecular aging and rejuvenation of human muscle stem cells

Very little remains known about the regulation of human organ stem cells (in general, and during the aging process), and most previous data were collected in short-lived rodents. We examined whether stem cell aging in rodents could be extrapolated to genetically and environmentally variable humans. Our findings establish key evolutionarily conserved mechanisms of human stem cell aging. We find that satellite cells are maintained in aged human skeletal muscle, but fail to activate in response to muscle attrition, due to diminished activation of Notch compounded by elevated transforming growth factor beta (TGF-β)/phospho Smad3 (pSmad3). Furthermore, this work reveals that mitogen-activated protein kinase (MAPK)/phosphate extracellular signal-regulated kinase (pERK) signalling declines in human muscle with age, and is important for activating Notch in human muscle stem cells. This molecular understanding, combined with data that human satellite cells remain intrinsically young, introduced novel therapeutic targets. Indeed, activation of MAPK/Notch restored ‘youthful’ myogenic responses to satellite cells from 70-year-old humans, rendering them similar to cells from 20-year-old humans. These findings strongly suggest that aging of human muscle maintenance and repair can be reversed by ‘youthful’ calibration of specific molecular pathways

Assessment of muscle function using hybrid PET/MRI:comparison of ¹⁸F-FDG PET and T2-weighted MRI for quantifying muscle activation in human subjects

PURPOSE: The aim of this study was to determine the relationship between relative glucose uptake and MRI T (2) changes in skeletal muscles following resistance exercise using simultaneous PET/MRI scans. METHODS: Ten young healthy recreationally active men (age 21 – 28 years) were injected with (18)F-FDG while activating the quadriceps of one leg with repeated knee extension exercises followed by hand-grip exercises for one arm. Immediately following the exercises, the subjects were scanned simultaneously with (18)F-FDG PET/MRI and muscle groups were evaluated for increases in (18)F-FDG uptake and MRI T (2) values. RESULTS: A significant linear correlation between (18)F-FDG uptake and changes in muscle T (2) (R (2) = 0.71) was found. for both small and large muscles and in voxel to voxel comparisons. Despite large intersubject differences in muscle recruitment, the linear correlation between (18)F-FDG uptake and changes in muscle T (2) did not vary among subjects. CONCLUSION: This is the first assessment of skeletal muscle activation using hybrid PET/MRI and the first study to demonstrate a high correlation between (18)F-FDG uptake and changes in muscle T (2) with physical exercise. Accordingly, it seems that changes in muscle T (2) may be used as a surrogate marker for glucose uptake and lead to an improved insight into the metabolic changes that occur with muscle activation. Such knowledge may lead to improved treatment strategies in patients with neuromuscular pathologies such as stroke, spinal cord injuries and muscular dystrophies