| Autor: |
Ferrara PJ; Molecular Medicine Program, University of Utah, Salt Lake City, Utah., Yee EM; Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah., Petrocelli JJ; Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah., Fix DK; Molecular Medicine Program, University of Utah, Salt Lake City, Utah., Hauser CT; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah., de Hart NMMP; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah., Mahmassani ZS; Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah., Reidy PT; Department of Kinesiology, Miami University, Oxford, Ohio., O'Connell RM; Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah., Drummond MJ; Molecular Medicine Program, University of Utah, Salt Lake City, Utah.; Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah.; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah. |
| Abstrakt: |
Poor recovery of muscle size and strength with aging coincides with a dysregulated macrophage response during the early stages of regrowth. Immunomodulation in the form of ex vivo cytokine (macrophage-colony stimulating factor) or polarized macrophage delivery has been demonstrated to improve skeletal muscle regeneration. However, it is unclear if these macrophage-promoting approaches would be effective to improve skeletal muscle recovery following disuse in aged animals. Here, we isolated bone marrow-derived macrophages from donor mice of different ages under various experimental conditions and polarized them into proinflammatory macrophages. Macrophages were delivered intramuscularly into young adult or aged recipient mice during the early recovery period following a period of hindlimb unloading (HU). Delivery of proinflammatory macrophages from donor young adults or aged mice was sufficient to increase muscle function of aged mice during the recovery period. Moreover, proinflammatory macrophages derived from aged donor mice collected during recovery were similarly able to increase muscle function of aged mice following disuse. In addition to the delivery of macrophages, we showed that the intramuscular injection of the cytokine, macrophage-colony stimulating factor, to the muscle of aged mice following HU was able to increase muscle macrophage content and muscle force production during recovery. Together, these results suggest that macrophage immunomodulation approaches in the form of ex vivo proinflammatory macrophage or macrophage-colony stimulating factor delivery during the early recovery phase following disuse atrophy were sufficient to restore the loss of aged skeletal muscle function. NEW & NOTEWORTHY A single intramuscular administration of polarized macrophages into muscles of aged mice following a bout of disuse atrophy was sufficient to improve functional recover similarly to young adults after disuse atrophy regardless of the age or experimental condition of the donor mice. Additionally, intramuscular delivery of macrophage-colony stimulating factor into aged mice was similarly effective. Targeting macrophage function early during the regrowth phase may be a novel tool to bolster muscle recovery in aging. |
