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Altered Relaxation and Mitochondria-Endoplasmic Reticulum Contacts Precede Major (Mal)Adaptations in Aging Skeletal
Ryan J Allen1, Ana Kronemberger1, Qian Shi2
1Department of Health and Human Physiology, Fraternal Order of Eagles Diabetes Research Center, College of Liberal Arts and Sciences, University of Iowa, Iowa City, Iowa, USA.
Aging Cell
|June 30, 2025
Summary
Aging muscle dysfunction (sarcopenia) involves early changes in mitochondria-endoplasmic reticulum contacts (MERCs), affecting muscle relaxation before force decline. Regular exercise preserves MERC structure and function, suggesting new therapeutic targets.
Area of Science:
- Muscle physiology
- Cellular biology
- Aging research
Background:
- Sarcopenia, age-related muscle dysfunction, increases morbidity and mortality.
- Cellular changes preceding sarcopenia, such as atrophy and fiber type switching, are poorly understood.
- Mitochondria and sarcoplasmic reticulum interactions at MERCs are crucial for muscle tension.
Purpose of the Study:
- Investigate early cellular changes in aging muscle, specifically at MERCs.
- Determine the impact of aging on MERC ultrastructure and proteome.
- Assess the role of exercise in mitigating age-related changes at MERCs.
Main Methods:
- Studied young adult and older mice.
- Analyzed muscle relaxation rate, excitation-contraction-relaxation (ECR) cycles, and maximal force.
- Examined MERC ultrastructure and mitochondria-associated ER membrane (MAM) protein composition.
- Profiled MAM proteins involved in key cellular processes.
Main Results:
- Aging slowed muscle relaxation and prolonged ECR cycles prior to significant force decrease or fiber type switching.
- Muscle MERC ultrastructure and MAM protein composition were altered early in aging, correlating with slower relaxation.
- Regular exercise maintained muscle relaxation rate and MERC ultrastructure in aging mice.
- Identified specific MAM proteins inversely regulated by aging and exercise, involved in metabolism, protein quality control, calcium homeostasis, cytoskeleton, and redox balance.
Conclusions:
- Early aging affects muscle MERC ultrastructure and MAM proteome, impacting muscle relaxation.
- These MERC changes precede major sarcopenia hallmarks like force decline and fiber switching.
- Exercise interventions can preserve MERC integrity and muscle function during aging.
- Targeting identified MAM proteins may offer strategies to combat age-related muscle dysfunction.
Keywords:
agingendoplasmic reticulumexercisemitochondriamitochondrial‐associated ER membranessarcopeniasarcoplasmic reticulumskeletal muscleMore Related Videos
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