Aged Muscle Demonstrates fiber- Type adaptations in response to mechanical overload, in the absence of myofiber hypertrophy, independent of satellite cell abundance

Jonah D. Lee, Christopher Fry, Jyothi Mula, Tyler J. Kirby, Janna R. Jackson, Fujun Liu, Lin Yang, Esther E. Dupont-Versteegden, John J. Mccarthy, Charlotte A. Peterson

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Although sarcopenia, age- Associated loss of muscle mass and strength, is neither accelerated nor exacerbated by depletion of muscle stem cells, satellite cells, we hypothesized that adaptation in sarcopenic muscle would be compromised. To test this hypothesis, we depleted satellite cells with tamoxifen treatment of Pax7CreER-DTA mice at 4 months of age, and 20 months later subjected the plantaris muscle to 2 weeks of mechanical overload. We found myofiber hypertrophy was impaired in aged mice regardless of satellite cell content. Even in the absence of growth, vehicle- Treated mice mounted a regenerative response, not apparent in tamoxifen- Treated mice. Further, myonuclear accretion occurred in the absence of growth, which was prevented by satellite cell depletion, demonstrating that myonuclear addition is insufficient to drive myofiber hypertrophy. Satellite cell depletion increased extracellular matrix content of aged muscle that was exacerbated by overload, potentially limiting myofiber growth. These results support the idea that satellite cells regulate the muscle environment, and that their loss during aging may contribute to fibrosis, particularly during periods of remodeling. Overload induced a fiber- Type composition improvement, independent of satellite cells, suggesting that aged muscle is very responsive to exercise-induced enhancement in oxidative capacity, even with an impaired hypertrophic response.

Original languageEnglish (US)
Pages (from-to)461-467
Number of pages7
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume71
Issue number4
DOIs
StatePublished - Apr 1 2016

Fingerprint

Hypertrophy
Muscles
Tamoxifen
Muscle Cells
Growth
Sarcopenia
Muscle Strength
Extracellular Matrix
Skeletal Muscle
Fibrosis
Stem Cells

Keywords

  • Fibrosis
  • Muscle overload
  • Regeneration
  • Sarcopenia
  • Satellite cells

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

Aged Muscle Demonstrates fiber- Type adaptations in response to mechanical overload, in the absence of myofiber hypertrophy, independent of satellite cell abundance. / Lee, Jonah D.; Fry, Christopher; Mula, Jyothi; Kirby, Tyler J.; Jackson, Janna R.; Liu, Fujun; Yang, Lin; Dupont-Versteegden, Esther E.; Mccarthy, John J.; Peterson, Charlotte A.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 71, No. 4, 01.04.2016, p. 461-467.

Research output: Contribution to journalArticle

Lee, Jonah D. ; Fry, Christopher ; Mula, Jyothi ; Kirby, Tyler J. ; Jackson, Janna R. ; Liu, Fujun ; Yang, Lin ; Dupont-Versteegden, Esther E. ; Mccarthy, John J. ; Peterson, Charlotte A. / Aged Muscle Demonstrates fiber- Type adaptations in response to mechanical overload, in the absence of myofiber hypertrophy, independent of satellite cell abundance. In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2016 ; Vol. 71, No. 4. pp. 461-467.
@article{e61cfc3c4f4746b48efb039ff3cd8ab7,
title = "Aged Muscle Demonstrates fiber- Type adaptations in response to mechanical overload, in the absence of myofiber hypertrophy, independent of satellite cell abundance",
abstract = "Although sarcopenia, age- Associated loss of muscle mass and strength, is neither accelerated nor exacerbated by depletion of muscle stem cells, satellite cells, we hypothesized that adaptation in sarcopenic muscle would be compromised. To test this hypothesis, we depleted satellite cells with tamoxifen treatment of Pax7CreER-DTA mice at 4 months of age, and 20 months later subjected the plantaris muscle to 2 weeks of mechanical overload. We found myofiber hypertrophy was impaired in aged mice regardless of satellite cell content. Even in the absence of growth, vehicle- Treated mice mounted a regenerative response, not apparent in tamoxifen- Treated mice. Further, myonuclear accretion occurred in the absence of growth, which was prevented by satellite cell depletion, demonstrating that myonuclear addition is insufficient to drive myofiber hypertrophy. Satellite cell depletion increased extracellular matrix content of aged muscle that was exacerbated by overload, potentially limiting myofiber growth. These results support the idea that satellite cells regulate the muscle environment, and that their loss during aging may contribute to fibrosis, particularly during periods of remodeling. Overload induced a fiber- Type composition improvement, independent of satellite cells, suggesting that aged muscle is very responsive to exercise-induced enhancement in oxidative capacity, even with an impaired hypertrophic response.",
keywords = "Fibrosis, Muscle overload, Regeneration, Sarcopenia, Satellite cells",
author = "Lee, {Jonah D.} and Christopher Fry and Jyothi Mula and Kirby, {Tyler J.} and Jackson, {Janna R.} and Fujun Liu and Lin Yang and Dupont-Versteegden, {Esther E.} and Mccarthy, {John J.} and Peterson, {Charlotte A.}",
year = "2016",
month = "4",
day = "1",
doi = "10.1093/gerona/glv033",
language = "English (US)",
volume = "71",
pages = "461--467",
journal = "Journals of Gerontology - Series A Biological Sciences and Medical Sciences",
issn = "1079-5006",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - Aged Muscle Demonstrates fiber- Type adaptations in response to mechanical overload, in the absence of myofiber hypertrophy, independent of satellite cell abundance

AU - Lee, Jonah D.

AU - Fry, Christopher

AU - Mula, Jyothi

AU - Kirby, Tyler J.

AU - Jackson, Janna R.

AU - Liu, Fujun

AU - Yang, Lin

AU - Dupont-Versteegden, Esther E.

AU - Mccarthy, John J.

AU - Peterson, Charlotte A.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Although sarcopenia, age- Associated loss of muscle mass and strength, is neither accelerated nor exacerbated by depletion of muscle stem cells, satellite cells, we hypothesized that adaptation in sarcopenic muscle would be compromised. To test this hypothesis, we depleted satellite cells with tamoxifen treatment of Pax7CreER-DTA mice at 4 months of age, and 20 months later subjected the plantaris muscle to 2 weeks of mechanical overload. We found myofiber hypertrophy was impaired in aged mice regardless of satellite cell content. Even in the absence of growth, vehicle- Treated mice mounted a regenerative response, not apparent in tamoxifen- Treated mice. Further, myonuclear accretion occurred in the absence of growth, which was prevented by satellite cell depletion, demonstrating that myonuclear addition is insufficient to drive myofiber hypertrophy. Satellite cell depletion increased extracellular matrix content of aged muscle that was exacerbated by overload, potentially limiting myofiber growth. These results support the idea that satellite cells regulate the muscle environment, and that their loss during aging may contribute to fibrosis, particularly during periods of remodeling. Overload induced a fiber- Type composition improvement, independent of satellite cells, suggesting that aged muscle is very responsive to exercise-induced enhancement in oxidative capacity, even with an impaired hypertrophic response.

AB - Although sarcopenia, age- Associated loss of muscle mass and strength, is neither accelerated nor exacerbated by depletion of muscle stem cells, satellite cells, we hypothesized that adaptation in sarcopenic muscle would be compromised. To test this hypothesis, we depleted satellite cells with tamoxifen treatment of Pax7CreER-DTA mice at 4 months of age, and 20 months later subjected the plantaris muscle to 2 weeks of mechanical overload. We found myofiber hypertrophy was impaired in aged mice regardless of satellite cell content. Even in the absence of growth, vehicle- Treated mice mounted a regenerative response, not apparent in tamoxifen- Treated mice. Further, myonuclear accretion occurred in the absence of growth, which was prevented by satellite cell depletion, demonstrating that myonuclear addition is insufficient to drive myofiber hypertrophy. Satellite cell depletion increased extracellular matrix content of aged muscle that was exacerbated by overload, potentially limiting myofiber growth. These results support the idea that satellite cells regulate the muscle environment, and that their loss during aging may contribute to fibrosis, particularly during periods of remodeling. Overload induced a fiber- Type composition improvement, independent of satellite cells, suggesting that aged muscle is very responsive to exercise-induced enhancement in oxidative capacity, even with an impaired hypertrophic response.

KW - Fibrosis

KW - Muscle overload

KW - Regeneration

KW - Sarcopenia

KW - Satellite cells

UR - http://www.scopus.com/inward/record.url?scp=84964799057&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964799057&partnerID=8YFLogxK

U2 - 10.1093/gerona/glv033

DO - 10.1093/gerona/glv033

M3 - Article

C2 - 25878030

AN - SCOPUS:84964799057

VL - 71

SP - 461

EP - 467

JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

SN - 1079-5006

IS - 4

ER -