Key result
Periostin reconstitution rescues age-impaired muscle regeneration by preventing fibro-fatty degeneration.
Why the study?
Aging impairs skeletal muscle regeneration by disrupting extracellular matrix integration and immunomodulatory functions of fibro/adipogenic progenitors, promoting fibro/fatty degeneration.
Does transplantation of young FAPs with high Periostin secretion restore inflammation resolution and muscle regeneration in aged muscle?
Does transplantation of young FAPs with high Periostin secretion restore inflammation resolution and muscle regeneration in aged muscle?
Periostin secreted by fibro/adipogenic progenitors is a critical niche factor that orchestrates successful skeletal muscle regeneration and prevents fibro/fatty degeneration during aging.
Periostin reconstitution merits exploration for age-related muscle decline; hypothesis-generating and requires clinical validation before practice change.
Summary Skeletal muscle regeneration depends on the function of fibro/adipogenic progenitors (FAPs). Here we show that aging impairs myogenic stem cells by disrupting the integration of extracellular matrix and immunomodulatory functions within the stem cell niche, thereby promoting fibro/fatty degeneration. We identify the FAP-secreted protein Periostin as a niche factor that is decreased in aged muscle and in circulation of aged humans with low-exercise lifestyle. Periostin controls FAP-expansion after injury and its depletion fate-regulates FAPs towards adipogenesis. This leads to delayed pro- to anti-inflammatory macrophage transition during regeneration. Transplantation of young FAPs with high Periostin secretion, but not Periostin-deficient FAPs, into aged muscle restores inflammation resolution and successful regeneration. Mechanistically, Periostin activates Focal adhesion kinase- and AKT-signaling in macrophages via integrins to promote an anti-inflammatory profile, which synchronizes matrix-derived mechanosensory signaling and immunomodulation. These results uncover a novel role of FAP-based regulation that orchestrates successful muscle regeneration and prevents fibro/fatty degeneration.
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García‐Carrizo et al. (2023) studied Skeletal muscle aging and regeneration. Aging and Periostin deficiency vs. Young age and wildtype Periostin expression was evaluated on Skeletal muscle regeneration and fibro/fatty degeneration. Aging impairs skeletal muscle regeneration by reducing FAP-secreted Periostin, leading to fibro/fatty degeneration and delayed inflammation resolution, which can be rescued by Periostin reconstitution.
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