Aging impairs mouse skeletal muscle macrophage polarization and muscle-specific abundance during recovery from disuse

• Published in: American journal of physiology: endocrinology and metabolism Vol. 317; no. 1; pp. E85 - E98
• Main Authors: Reidy, Paul T, McKenzie, Alec I, Mahmassani, Ziad S, Petrocelli, Jonathan J, Nelson, Daniel B, Lindsay, Catherine C, Gardner, James E, Morrow, Vincent R, Keefe, Alexandra C, Huffaker, Thomas B, Stoddard, Greg J, Kardon, Gabrielle, O'Connell, Ryan M, Drummond, Micah J
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.07.2019
• Series: Immunometabolic Cross-Talk and Regulation of Endocrine and Metabolic Functions
• Subjects: Aging; Aging - physiology; Animals; Cell Polarity - physiology; Cell suspensions; Flow cytometry; Hindlimb Suspension - physiology; Immune system; Immunofluorescence; Macrophage Activation - physiology; Macrophages; Macrophages - physiology; Major histocompatibility complex; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal - cytology; Muscle, Skeletal - immunology; Muscle, Skeletal - pathology; Muscles; Muscular Atrophy - pathology; Muscular Atrophy - rehabilitation; Musculoskeletal system; Phenotypes; Physical Conditioning, Animal - physiology; Polarization; Regrowth; Rodents; Skeletal muscle; Soleus muscle; Unloading; immune; regrowth; supporting cells; hindlimb suspension
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00422.2018

Impaired recovery of aged muscle following a disuse event is an unresolved issue facing the older adult population. Although investigations in young animals have suggested that rapid regrowth of skeletal muscle following a disuse event entails a coordinated involvement of skeletal muscle macrophages, this phenomenon has not yet been thoroughly tested as an explanation for impaired muscle recovery in aging. To examine this hypothesis, young (4-5 mo) and old (24-26 mo) male mice were examined as controls following 2 wk of hindlimb unloading (HU) and following 4 (RL4) and 7 (RL7) days of reloading after HU. Muscles were harvested to assess muscle weight, myofiber-specifc cross-sectional area, and skeletal muscle macrophages via immunofluorescence. Flow cytometry was used on gastrocnemius and soleus muscle (at RL4) single-cell suspensions to immunophenotype skeletal muscle macrophages. Our data demonstrated impaired muscle regrowth in aged compared with young mice following disuse, which was characterized by divergent muscle macrophage polarization patterns and muscle-specifc macrophage abundance. During reloading, young mice exhibited the classical increase in M1-like (MHC II CD206 ) macrophages that preceeded the increase in percentage of M2-like macrophages (MHC II CD206 ); however, old mice did not demonstrate this pattern. Also, at RL4, the soleus demonstrated reduced macrophage abundance with aging. Together, these data suggest that dysregulated macrophage phenotype patterns in aged muscle during recovery from disuse may be related to impaired muscle growth. Further investigation is needed to determine whether the dysregulated macrophage response in the old during regrowth from disuse is related to a reduced ability to recruit or activate specific immune cells.