Age-related fatigue is associated with reduced mitochondrial function in peripheral blood mononuclear cells.

Abstract

Fatigue is a complex syndrome associated with exhaustion not relieved by sleep. It occurs frequently in older adults in the context of chronic disease and is associated with decreased physical capacity. Whether a mitochondrial dysfunction and therefore an impaired energy production might contribute to the development of fatigue during aging is yet unknown. The aim of this study was to evaluate mitochondrial respiration of peripheral blood mononuclear cells (PBMCs) in older patients with and without fatigue. Fatigue was determined according to the Brief Fatigue Inventory. Mitochondrial respiration of freshly isolated PBMCs was investigated by high-resolution respirometry using the Oroboros Oxygraph-O2k. Functional impairment and depressive symptoms were assessed using questionnaires. 23 geriatric patients (77.8±4.9years; 43.5% female) with fatigue and 22 without fatigue (75.4±5.4years; 45.5% female) were analyzed. Patients with fatigue exhibited more functional limitations and more depressive symptoms. High-resolution respirometry of intact PBMCs revealed a lower routine (4.82±1.14pmol/s versus 5.89±1.90pmol/s, p=0.041) and maximum (6.55±1.51pmol/s versus 8.43±3.67pmol/s, p=0.013) oxygen consumption rate, resulting in a reduced ATP-linked respiration (4.26±1.00pmol/s versus 5.09±1.53pmol/s, p=0.035) of PBMCs from geriatric patients with fatigue compared to controls without. This short report shows that in this group of older patients, fatigue is associated with lower PBMC mitochondrial respiration. Whether the impaired mitochondrial respiration is accompanied by a reduced mitochondrial activity in other organs (e.g. muscle) remains to be elucidated.