Aging-related effects of bed rest followed by eccentric exercise rehabilitation on skeletal muscle macrophages and insulin sensitivity

Paul T. Reidy; Catherine C. Lindsay; Alec I. McKenzie; Christopher S. Fry; Mark A. Supiano; Robin L. Marcus; Paul C. LaStayo; Micah J. Drummond

doi:10.1016/j.exger.2017.07.001

Aging-related effects of bed rest followed by eccentric exercise rehabilitation on skeletal muscle macrophages and insulin sensitivity

Paul T. Reidy, Catherine C. Lindsay, Alec I. McKenzie, Christopher S. Fry, Mark A. Supiano, Robin L. Marcus, Paul C. LaStayo, Micah J. Drummond

Athletic Training and Clinical Nutrition

Research output: Contribution to journal › Article › peer-review

57 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	37-49
Number of pages	13
Journal	Experimental Gerontology
Volume	107
DOIs	https://doi.org/10.1016/j.exger.2017.07.001
State	Published - Jul 1 2018

Bibliographical note

Publisher Copyright:
© 2017 Elsevier Inc.

Funding

This project is supported by the American Federation on Aging Research and grants from the National Institute on Aging (AG038556, AG050781), the National Centre for Advancing Translational Sciences (1ULTR001067) and University of Utah's Centre on Aging. CCL participated in the Medical Student Research Program at the University of Utah School of Medicine and was supported by the Medical Student Training in Aging Research program sponsored by the American Federation for Aging. This program is supported by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award (T35DK103596) from the National Institute of Diabetes and Digestive and Kidney Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. PTR was supported by a Jeanne B Kempner Fellowship. This project is supported by the American Federation on Aging Research and grants from the National Institute on Aging ( AG038556 , AG050781 ), the National Centre for Advancing Translational Sciences ( 1ULTR001067 ) and University of Utah 's Centre on Aging. CCL participated in the Medical Student Research Program at the University of Utah School of Medicine and was supported by the Medical Student Training in Aging Research program sponsored by the American Federation for Aging. This program is supported by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award (T35DK103596) from the National Institute of Diabetes and Digestive and Kidney Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. PTR was supported by a Jeanne B Kempner Fellowship.

Funders	Funder number
American Federation for Aging Research
University of Utah 's Centre on Aging
University of Utah's Centre on Aging
National Institutes of Health (NIH)
National Institute on Aging	R01AG050781, AG038556
National Institute on Aging
National Institute of Diabetes and Digestive and Kidney Diseases	T35DK103596
National Institute of Diabetes and Digestive and Kidney Diseases
American Federation for Aging Research
National Center for Advancing Translational Sciences (NCATS)	1ULTR001067
National Center for Advancing Translational Sciences (NCATS)
University of Utah Health
School of Medicine, department of Internal Medicine

Keywords

Aging
Atrophy
Eccentric exercise
Immune cells
M1
M2
Muscle-resident
Recovery
Regrowth
Rehabilitation
Training

ASJC Scopus subject areas

Biochemistry
Aging
Molecular Biology
Genetics
Endocrinology
Cell Biology

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title = "Aging-related effects of bed rest followed by eccentric exercise rehabilitation on skeletal muscle macrophages and insulin sensitivity",

abstract = " 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 \textasciitilde{} 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.",

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AU - Reidy, Paul T.

AU - Lindsay, Catherine C.

AU - McKenzie, Alec I.

AU - Fry, Christopher S.

AU - Supiano, Mark A.

AU - Marcus, Robin L.

AU - LaStayo, Paul C.

AU - Drummond, Micah J.

PY - 2018/7/1

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N2 - 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.

AB - 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.

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KW - Eccentric exercise

KW - Immune cells

KW - M1

KW - M2

KW - Muscle-resident

KW - Recovery

KW - Regrowth

KW - Rehabilitation

KW - Training

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Aging-related effects of bed rest followed by eccentric exercise rehabilitation on skeletal muscle macrophages and insulin sensitivity

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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