Related Experiment Video
Updated: May 30, 2025
In Situ Immunofluorescent Staining of Autophagy in Muscle Stem Cells
Published on: June 12, 2017
Tissue-resident skeletal muscle macrophages promote recovery from viral pneumonia-induced sarcopenia in normal aging
Constance E Runyan1, Lucy Luo1, Lynn C Welch1
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Simpson Querrey Lung Institute for Translational Sciences. Northwestern University. Chicago, IL, USA.
Abstract:
Sarcopenia, which diminishes lifespan and healthspan in the elderly, is commonly exacerbated by viral pneumonia, including influenza and COVID-19. In a study of influenza A pneumonia in mice, young mice fully recovered from sarcopenia, while older mice did not. We identified a population of tissue-resident skeletal muscle macrophages that form a spatial niche with satellite cells and myofibers in young mice but are lost with age. Mice with a gain-of-function mutation in the Mertk receptor maintained this macrophage-myofiber interaction during aging and fully recovered from influenza-induced sarcopenia. In contrast, deletion of Mertk in macrophages or loss of Cx3cr1 disrupted this niche, preventing muscle regeneration. Heterochronic parabiosis did not restore the niche in old mice. These findings suggest that age-related loss of Mertk in muscle tissue-resident macrophages disrupts the cellular signaling necessary for muscle regeneration after viral pneumonia, offering a potential target to mitigate sarcopenia in aging.
Insights
Aging impairs muscle regeneration after viral pneumonia. A specific macrophage-myofiber interaction, crucial for recovery, is lost with age but can be preserved by targeting the Mertk receptor, offering a potential therapeutic strategy for age-related sarcopenia.
Area of Science:
- Gerontology
- Immunology
- Skeletal Muscle Biology
Background:
- Sarcopenia, a decline in muscle mass and function, worsens with age and is exacerbated by viral infections like influenza and COVID-19.
- Age-related changes in the skeletal muscle microenvironment contribute to impaired regeneration.
- Tissue-resident macrophages play a role in muscle repair, but their function declines with aging.
Purpose of the Study:
- To investigate the mechanisms underlying age-related sarcopenia following viral pneumonia.
- To identify cellular players and molecular pathways involved in impaired muscle regeneration in older mice.
- To explore potential therapeutic targets for mitigating age-related muscle loss after viral infections.
Main Methods:
- A mouse model of influenza A pneumonia was used to study age-dependent sarcopenia.
- Immunohistochemistry and cell-specific gene manipulation (Mertk, Cx3cr1) were employed to analyze macrophage-satellite cell-myofiber interactions.
- Gain-of-function mutations in Mertk and heterochronic parabiosis were utilized to assess their impact on muscle regeneration.
Main Results:
- Young mice recovered from influenza-induced sarcopenia, while older mice did not.
- A specific population of tissue-resident skeletal muscle macrophages interacting with satellite cells and myofibers was identified in young mice but lost in aged mice.
- Preserving the macrophage-myofiber niche via Mertk gain-of-function mutation restored muscle regeneration in aged mice.
- Deletion of Mertk or Cx3cr1 disrupted this niche and prevented muscle recovery.
Conclusions:
- Age-related loss of Mertk signaling in muscle-resident macrophages disrupts the cellular niche essential for muscle regeneration after viral pneumonia.
- Targeting Mertk in macrophages presents a potential therapeutic strategy to combat age-related sarcopenia and improve recovery from viral infections in the elderly.
