aDepartment of Physical Therapy and Athletic Training, University of Utah, 520 Wakara Way, Salt Lake City, UT 84018, USAbSchool of Medicine, University of Utah, 30 N. 1900 E, Salt Lake City, UT 84132, USAcDepartment of Nutrition and Metabolism, University of Texas Medical Branch, Galveston, TX 77550, USAdDivision of Geriatrics, 30 N 1900 E, Room 4B120, University of Utah, Salt Lake City, UT 84132, USAeVA Salt Lake City Geriatric Research, Education, and Clinical Center, Salt Lake City, UT 84148, USAfDepartment of Nutrition and Integrative Physiology, University of Utah, 250 S. 1850 E, RM 214, Salt Lake City, UT 84112, USA
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The pro- and anti-inflammatory macrophages are associated with insulin sensitivity and skeletal muscle regeneration. Infiltrating macrophages in skeletal muscle during a period of physical inactivity and subsequent reloading/rehabilitation in older adults is unknown, but may provide insight into mechanisms related to the development of metabolic disease and changes in muscle cell size. The purpose of this study was to determine if skeletal muscle macrophage infiltration is modulated differently between young and older adults after bed rest and exercise rehabilitation and if these responses are related to muscle and insulin sensitivity changes. 14 young and 9 older adults underwent 5-days of bed rest followed by 8-weeks of lower limb eccentric exercise rehabilitation (REHAB). Dual-energy X-ray absorptiometry, magnetic resonance imaging and myofiber analysis were used to identify muscle morphology and CLIX-IR and CLIX-β were used to assess insulin sensitivity. Skeletal muscle macrophages, CD68 (pan), CD11b (M1), CD163 (M2), CD206 (M2), were characterized using immunohistochemistry and gene expression. Insulin sensitivity, independent of age, decreased ˜ 38% following bed rest and was restored following REHAB. We found robust age-related differences in muscle atrophy during bed rest, yet older and younger adults equally hypertrophied during REHAB. Interestingly, there were age-related differences in macrophage content (CD68+ CD11b+ and CD68+ CD11b− cells) but both young and old similarly increased macrophages with REHAB. Satellite cell changes during rehab corresponded to macrophage content changes. Muscle tissue resident macrophages and gene expression, were not associated with changes in insulin sensitivity following bed rest and REHAB. These data suggest that muscle macrophages are modulated as a result of exercise rehabilitation following bed rest and may more associated with muscle regrowth/hypertrophy rather than insulin sensitivity in young or older adults.This trial was registered at clinicaltrials.gov as NCT01669590.HIGHLIGHTSOlder adults (vs young) experienced atrophy during bed rest, but both groups gained lean mass similarly after rehabilitation.Insulin sensitivity decreased after bed rest and returned to baseline levels after rehabilitation, independent of age.There were age-related differences in skeletal muscle macrophages, but both groups increased macrophages after rehabilitation.Changes in muscle macrophages corresponded to changes in satellite cells, but not insulin sensitivity during rehabilitation.