Aging disrupts MANF-mediated immune modulation dur
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Aging disrupts MANF-mediated immune modulation during skeletal muscle regeneration
Neuza S. Sousa, Margarida F. Brás, Inês B. Antunes, Päivi Lindholm, Joana Neves & Pedro Sousa-Victor
Nature Aging volume 3, pages585–599 (2023)Cite this article
Published: 23 March 2023
https://www.nature.com/articles/s43587-023-00382-5
Abstract
Age-related decline in skeletal muscle regenerative capacity is multifactorial, yet the contribution of immune dysfunction to regenerative failure is unknown. Macrophages are essential for effective debris clearance and muscle stem cell activity during muscle regeneration, but the regulatory mechanisms governing macrophage function during muscle repair are largely unexplored. 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 mesencephalic astrocyte-derived neurotrophic factor (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 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 MANF levels is a viable strategy to improve myeloid response and regenerative capacity in aged muscle.
Immune modulation by MANF improves regeneration in aged skeletal muscle
Nature Aging volume 3, pages477–478 (2023)Cite this article
Published: 07 April 2023
Despite the central role of immune regulation in tissue repair, the contribution of immune dysfunction to regenerative failure in aging is mostly unknown. We discovered a mechanism of immune modulation that operates during skeletal muscle regeneration that is compromised in aged animals and can be harnessed to improve regenerative capacity in aging.
Neuza S. Sousa, Margarida F. Brás, Inês B. Antunes, Päivi Lindholm, Joana Neves & Pedro Sousa-Victor
Nature Aging volume 3, pages585–599 (2023)Cite this article
Published: 23 March 2023
https://www.nature.com/articles/s43587-023-00382-5
Abstract
Age-related decline in skeletal muscle regenerative capacity is multifactorial, yet the contribution of immune dysfunction to regenerative failure is unknown. Macrophages are essential for effective debris clearance and muscle stem cell activity during muscle regeneration, but the regulatory mechanisms governing macrophage function during muscle repair are largely unexplored. 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 mesencephalic astrocyte-derived neurotrophic factor (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 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 MANF levels is a viable strategy to improve myeloid response and regenerative capacity in aged muscle.
Immune modulation by MANF improves regeneration in aged skeletal muscle
Nature Aging volume 3, pages477–478 (2023)Cite this article
Published: 07 April 2023
Despite the central role of immune regulation in tissue repair, the contribution of immune dysfunction to regenerative failure in aging is mostly unknown. We discovered a mechanism of immune modulation that operates during skeletal muscle regeneration that is compromised in aged animals and can be harnessed to improve regenerative capacity in aging.
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