title: Idiopathic chronic fatigue in older adults is linked to impaired mitochondrial content and biogenesis signaling in skeletal muscle.
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.
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, USA.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Wawrzyniak
authors.affiliation: Department of Aging and Geriatric Research, Division of Biology of Aging, University of Florida, Gainesville, Florida, USA.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Joseph
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Levin
authors.affiliation: Department of Aging and Geriatric Research, Division of Biology of Aging, University of Florida, Gainesville, Florida, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Gundermann
authors.affiliation: Department of Aging and Geriatric Research, Division of Biology of Aging, University of Florida, Gainesville, Florida, USA.
authors.forename: Christiaan
authors.initials: C
authors.lastname: Leeuwenburgh
authors.affiliation: Department of Aging and Geriatric Research, Division of Biology of Aging, University of Florida, Gainesville, Florida, USA.
authors.forename: Bhanuprasad
authors.initials: B
authors.lastname: Sandesara
authors.affiliation: Department of Aging and Geriatric Research, Division of Biology of Aging, University of Florida, Gainesville, Florida, USA.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Manini
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Adhihetty
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D005221:Fatigue / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism; D015673:Fatigue Syndrome, Chronic / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D051265:NF-E2-Related Factor 1 / Q000378:metabolism; D018384:Oxidative Stress; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D015398:Signal Transduction; D056566:Sirtuin 3 / Q000378:metabolism; D011795:Surveys and Questionnaires
chemical_list: D000975:Antioxidants; D051265:NF-E2-Related Factor 1; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D045304:Cytochromes c; C466093:SIRT3 protein, human; D056566:Sirtuin 3
keywords: Gerotarget; PGC-1α; fatigue; mitochondria; skeletal muscle