RT Journal Article
SR Electronic
T1 Ageing disrupts MANF-mediated immune modulation during skeletal muscle regeneration
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.07.20.500588
DO 10.1101/2022.07.20.500588
A1 Neuza S. Sousa
A1 Margarida F. Brás
A1 Inês B. Antunes
A1 Päivi Lindholm
A1 Joana Neves
A1 Pedro Sousa-Victor
YR 2022
UL http://biorxiv.org/content/early/2022/07/21/2022.07.20.500588.abstract
AB Age-related decline in skeletal muscle regenerative capacity is multifactorial, yet, the contribution of immune dysfunction to regenerative failure is unknown. Here, we uncover a new mechanism of immune modulation operating during skeletal muscle regeneration that is disrupted in aged animals and relies on the regulation of macrophage function. The immune modulator MANF is induced following muscle injury in young mice, but not in aged animals, and its expression is essential for regenerative success. Regenerative impairments in the aged muscle are associated with defects in the repair-associated myeloid response similar to those found in MANF-deficient models and could be improved through MANF delivery. We propose that restoring the myeloid response through immune modulation is a promising therapeutic strategy to improve the regenerative capacity of aged muscles.Competing Interest StatementThe authors have declared no competing interest.