Abstract
Fatigue is a symptom of many diseases, but it can also manifest as a unique medical condition, such as idiopathic chronic fatigue (ICF). While the prevalence of ICF increases with age, mitochondrial content and function decline with age, which may contribute to ICF. The purpose of this study was to determine whether skeletal muscle mitochondrial dysregulation and oxidative stress is linked to ICF in older adults. Sedentary, old adults (n = 48, age 72.4 ± 5.3 years) were categorized into ICF and non-fatigued (NF) groups based on the FACIT-Fatigue questionnaire. ICF individuals had a FACIT score one standard deviation below the mean for non-anemic adults > 65 years and were excluded according to CDC diagnostic criteria for ICF. Vastus lateralis muscle biopsies were analyzed, showing reductions in mitochondrial content and suppression of mitochondrial regulatory proteins Sirt3, PGC-1α, NRF-1, and cytochrome c in ICF compared to NF. Additionally, mitochondrial morphology proteins, antioxidant enzymes, and lipid peroxidation were unchanged in ICF individuals. Our data suggests older adults with ICF have reduced skeletal muscle mitochondrial content and biogenesis signaling that cannot be accounted for by increased oxidative damage.
Highlights
This is orchestrated by the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) that acts to increase the expression of numerous genes involved in mitochondrial biogenesis including nuclear respiratory factors 1 and 2 (NRF-1, NRF-2) and mitochondrial transcription factor A (TFAM) [7,8,9,10,11]
As expected, fatigued participants had higher Functional assessment of chronic illness therapy (FACIT)-F scores, but there were no differences in age, gender, and ethnicity were observed between the two groups
The idiopathic chronic fatigue” (ICF) group had a slightly higher (12%) body mass index, reported more depressionlike symptoms on the Center for Epidemiological Studies Depression Scale (CES-D) and was more likely to be treated for hypertension
Summary
Smits et al (2011) showed that skeletal muscle from younger patients with chronic fatigue syndrome (CFS) exhibited no change in mitochondrial respiratory chain complex activities or ATP production but overall mitochondrial content was significantly reduced compared to controls [31]. Patients with CFS have elevated markers of oxidative damage in muscle [33] and plasma [34], which may stem from the overproduction of damaging free radicals resulting from impaired mitochondrial function Despite this limited evidence for mitochondrial involvement in CFS, there are no studies to date that have comprehensively investigated mitochondrial function and regulation in an aged population with ICF [35]. Our study used stringent eligibility criteria, analogous to the criteria for diagnosing CFS such that outright and subclinical comorbidities commonly associated with fatigue were excluded from the study to minimize the contamination of underlying medical conditions
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