Title | Chronic muscle weakness and mitochondrial dysfunction in the absence of sustained atrophy in a preclinical sepsis model. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Owen AM, Patel SP, Smith JD, Balasuriya BK, Mori SF, Hawk GS, Stromberg AJ, Kuriyama N, Kaneki M, Rabchevsky AG, Butterfield TA, Esser KA, Peterson CA, Starr ME, Saito H |
Journal | Elife |
Volume | 8 |
Date Published | 2019 12 03 |
ISSN | 2050-084X |
Keywords | Animals, Atrophy, Disease Models, Animal, Female, Humans, Male, Mice, Mice, Inbred C57BL, Middle Aged, Mitochondria, Muscle, Mitochondrial Diseases, Muscle Weakness, Muscle, Skeletal, Quality of Life, Sepsis |
Abstract | Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of survivors. Our data suggest that sustained mitochondrial dysfunction, rather than atrophy alone, underlies chronic sepsis-induced muscle weakness. This study emphasizes that conventional efforts that aim to recover muscle quantity will likely remain ineffective for regaining strength and improving quality of life after sepsis until deficiencies in muscle quality are addressed. |
DOI | 10.7554/eLife.49920 |
Alternate Journal | Elife |
PubMed ID | 31793435 |
PubMed Central ID | PMC6890461 |
Grant List | 85600 / / Shriners Hospitals for Children / International R01 AG039732 / AG / NIA NIH HHS / United States P30 AG028740 / AG / NIA NIH HHS / United States F31 GM117868 / GM / NIGMS NIH HHS / United States R01 GM115552 / GM / NIGMS NIH HHS / United States R01 GM126181 / GM / NIGMS NIH HHS / United States R01 AG390732 / AG / NIA NIH HHS / United States R01 GM129532 / GM / NIGMS NIH HHS / United States R01 AG055359 / AG / NIA NIH HHS / United States R01 GM117298 / GM / NIGMS NIH HHS / United States |