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 Fry, Mark A. Supiano, Robin L. Marcus, Paul C. LaStayo, Micah J. Drummond

Research output: Contribution to journalArticle

  • 4 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.

LanguageEnglish (US)
JournalExperimental Gerontology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Exercise Therapy
Bed Rest
Macrophages
Patient rehabilitation
Muscle
Insulin Resistance
Skeletal Muscle
Aging of materials
Insulin
Rehabilitation
Muscles
Young Adult
Gene expression
Gene Expression
Muscular Atrophy
Metabolic Diseases
Photon Absorptiometry
Cell Size
Muscle Cells
Hypertrophy

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

Cite this

Aging-related effects of bed rest followed by eccentric exercise rehabilitation on skeletal muscle macrophages and insulin sensitivity. / Reidy, Paul T.; Lindsay, Catherine C.; McKenzie, Alec I.; Fry, Christopher; Supiano, Mark A.; Marcus, Robin L.; LaStayo, Paul C.; Drummond, Micah J.

In: Experimental Gerontology, 01.01.2018.

Research output: Contribution to journalArticle

Reidy, Paul T. ; Lindsay, Catherine C. ; McKenzie, Alec I. ; Fry, Christopher ; Supiano, Mark A. ; Marcus, Robin L. ; LaStayo, Paul C. ; Drummond, Micah J. / Aging-related effects of bed rest followed by eccentric exercise rehabilitation on skeletal muscle macrophages and insulin sensitivity. In: Experimental Gerontology. 2018.
@article{55cccf8f0f5e4233b66779947c39ec3e,
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 ~ 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.",
keywords = "Aging, Atrophy, Eccentric exercise, Immune cells, M1, M2, Muscle-resident, Recovery, Regrowth, Rehabilitation, Training",
author = "Reidy, {Paul T.} and Lindsay, {Catherine C.} and McKenzie, {Alec I.} and Christopher Fry and Supiano, {Mark A.} and Marcus, {Robin L.} and LaStayo, {Paul C.} and Drummond, {Micah J.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.exger.2017.07.001",
language = "English (US)",
journal = "Experimental Gerontology",
issn = "0531-5565",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Aging-related effects of bed rest followed by eccentric exercise rehabilitation on skeletal muscle macrophages and insulin sensitivity

AU - Reidy, Paul T.

AU - Lindsay, Catherine C.

AU - McKenzie, Alec I.

AU - Fry, Christopher

AU - Supiano, Mark A.

AU - Marcus, Robin L.

AU - LaStayo, Paul C.

AU - Drummond, Micah J.

PY - 2018/1/1

Y1 - 2018/1/1

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.

KW - Aging

KW - Atrophy

KW - Eccentric exercise

KW - Immune cells

KW - M1

KW - M2

KW - Muscle-resident

KW - Recovery

KW - Regrowth

KW - Rehabilitation

KW - Training

UR - http://www.scopus.com/inward/record.url?scp=85044196119&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044196119&partnerID=8YFLogxK

U2 - 10.1016/j.exger.2017.07.001

DO - 10.1016/j.exger.2017.07.001

M3 - Article

JO - Experimental Gerontology

T2 - Experimental Gerontology

JF - Experimental Gerontology

SN - 0531-5565

ER -