miR-24 and its target gene Prdx6 regulate viability and senescence of myogenic progenitors during aging.

Ana Soriano-Arroquia, John Gostage, Qin Xia, David Bardell, Rachel McCormick, Eugene McCloskey, Ilaria Bellantuono, Peter Clegg, Brian McDonagh, Katarzyna Goljanek-Whysall

Aging cell 2021 Oct

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Satellite cell-dependent skeletal muscle regeneration declines during aging. Disruptions within the satellite cells and their niche, together with alterations in the myofibrillar environment, contribute to age-related dysfunction and defective muscle regeneration. In this study, we demonstrated an age-related decline in satellite cell viability and myogenic potential and an increase in ROS and cellular senescence. We detected a transient upregulation of miR-24 in regenerating muscle from adult mice and downregulation of miR-24 during muscle regeneration in old mice. FACS-sorted satellite cells were characterized by decreased levels of miR-24 and a concomitant increase in expression of its target: Prdx6. Using GFP reporter constructs, we demonstrated that miR-24 directly binds to its predicted site within Prdx6 mRNA. Subtle changes in Prdx6 levels following changes in miR-24 expression indicate miR-24 plays a role in fine-tuning Prdx6 expression. Changes in miR-24 and Prdx6 levels were associated with altered mitochondrial ROS generation, increase in the DNA damage marker: phosphorylated-H2Ax and changes in viability, senescence, and myogenic potential of myogenic progenitors from mice and humans. The effects of miR-24 were more pronounced in myogenic progenitors from old mice, suggesting a context-dependent role of miR-24 in these cells, with miR-24 downregulation likely a part of a compensatory response to declining satellite cell function during aging. We propose that downregulation of miR-24 and subsequent upregulation of Prdx6 in muscle of old mice following injury are an adaptive response to aging, to maintain satellite cell viability and myogenic potential through regulation of mitochondrial ROS and DNA damage pathways. © 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.

Citation

Ana Soriano-Arroquia, John Gostage, Qin Xia, David Bardell, Rachel McCormick, Eugene McCloskey, Ilaria Bellantuono, Peter Clegg, Brian McDonagh, Katarzyna Goljanek-Whysall. miR-24 and its target gene Prdx6 regulate viability and senescence of myogenic progenitors during aging. Aging cell. 2021 Oct;20(10):e13475