Research Papers: Gerotarget (Focus on Aging):

Idiopathic chronic fatigue in older adults is linked to impaired mitochondrial content and biogenesis signaling in skeletal muscle

Nicholas R. Wawrzyniak, Anna-Maria Joseph, David G. Levin, David M. Gundermann, Christiaan Leeuwenburgh, Bhanuprasad Sandesara, Todd M. Manini and Peter J. Adhihetty _

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Oncotarget. 2016; 7:52695-52709. https://doi.org/10.18632/oncotarget.10685

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Nicholas R. Wawrzyniak1, Anna-Maria Joseph2, David G. Levin1, David M. Gundermann2, Christiaan Leeuwenburgh2, Bhanuprasad Sandesara2, Todd M. Manini2 and Peter J. Adhihetty1

1 Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, USA

2 Department of Aging and Geriatric Research, Division of Biology of Aging, University of Florida, Gainesville, Florida, USA

Correspondence to:

Peter J. Adhihetty, email:

Todd M. Manini, email:

Keywords: fatigue; skeletal muscle; mitochondria; PGC-1α; Gerotarget

Received: January 11, 2016 Accepted: June 09, 2016 Published: July 18, 2016


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.

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