Abstract
A common characteristic of aging is defective regeneration of skeletal muscle. The molecular pathways underlying age-related decline in muscle regenerative potential remain elusive. microRNAs are novel gene regulators controlling development and homeostasis and the regeneration of most tissues, including skeletal muscle. Here, we use satellite cells and primary myoblasts from mice and humans and an in vitro regeneration model, to show that disrupted expression of microRNA-143-3p and its target gene, Igfbp5, plays an important role in muscle regeneration in vitro. We identified miR-143 as a regulator of the insulin growth factor-binding protein 5 (Igfbp5) in primary myoblasts and show that the expression of miR-143 and its target gene is disrupted in satellite cells from old mice. Moreover, we show that downregulation of miR-143 during aging may act as a compensatory mechanism aiming at improving myogenesis efficiency; however, concomitant upregulation of miR-143 target gene, Igfbp5, is associated with increased cell senescence, thus affecting myogenesis. Our data demonstrate that dysregulation of miR-143-3p:Igfbp5 interactions in satellite cells with age may be responsible for age-related changes in satellite cell function.
Highlights
Age-related loss of skeletal muscle mass and function results in frailty, decline in strength and decrease in quality of life of older people
To investigate whether miR-143 may play a role during muscle regeneration, miR-143 expression was analysed by qPCR during muscle
Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd
Summary
Age-related loss of skeletal muscle mass and function results in frailty, decline in strength and decrease in quality of life of older people. Regeneration of adult skeletal muscle is largely dependent on satellite cell population (Morgan & Partridge, 2003). The availability and functionality of satellite cells determine effective regeneration. Aging-related changes in satellite cell number and properties, such as susceptibility to apoptosis and ability to proliferate, have been shown in humans and rodents The presence of senescent satellite cells in old mice and humans characterized by increased expression p16INK4a and decreased phosphorylation of the retinoblastoma (RB) protein was shown (Sousa-Victor et al, 2014)
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