Short reportAge-related fatigue is associated with reduced mitochondrial function in peripheral blood mononuclear cells
Introduction
Fatigue is a complex syndrome described as persistent exhaustion not relieved by sleep that affects the capacity to execute mental and physical activities (Zengarini et al., 2015) and is known to frequently occur in chronic disease and malnutrition (Franz et al., 2019a). Moreover, fatigue negatively influences quality of life and is a predictor for disability and mortality (Moreh et al., 2010). Due to a prevalence of 29–68% in community-dwelling older adults and its detrimental effects, it is crucial to understand the manifestation of fatigue (Moreh et al., 2010). However, the underlying molecular mechanisms and the pathophysiology of fatigue are yet not fully understood (Zengarini et al., 2015). Mitochondria can be linked to various processes associated with aging such as formation of reactive oxygen species, inflammation, cellular senescence and decline of tissue and organ function (Sun et al., 2016). Furthermore, mitochondrial functions such as mitochondrial dynamics and respiratory capacity decline with age (Sebastian et al., 2017). As circulating blood cells e.g. peripheral blood mononuclear cells (PBMCs) are able to reflect ongoing metabolic stress, they represent a suitable tool to evaluate mitochondrial bioenergetics in the clinical setting (Ost et al., 2018). Impaired mitochondrial function in PBMCs has been observed in i.a. major depression (Karabatsiakis et al., 2014) as well as sepsis (Cheng et al., 2016) and associations of mitochondrial respiration with gait speed, grip strength and inflammation have been shown (Tyrrell et al., 2015a; Tyrrell et al., 2015b). It has been suggested that impaired bioenergetics e.g. mitochondrial respiration, might contribute to the pathogenesis of chronic fatigue (Tomas et al., 2020). Tomas et al. recently reported altered mitochondrial function in PBMCs in younger patients with chronic fatigue syndrome (Tomas et al., 2020). However, mitochondrial function in PBMCs (or other tissues) has yet not been studied in older adults with fatigue. In this short report we therefore evaluated bioenergetic profiles in older patients with and without fatigue and explored a potential association with functional impairment.
Section snippets
Participants
This is an analysis of a study described elsewhere (Franz et al., 2019b). In brief, geriatric patients above 60 years, without cognitive impairment (mini mental state examination score ≥ 24) and without severe neurodegenerative disease, were consecutively recruited upon admission to hospital. Additionally, to in order to investigate cancer-unrelated fatigue, patients with cancer were not included. All participants signed written informed consent and the study was approved by the ethics
Results
Forty-five patients were included in this analysis and their characteristics are listed in Table 1. Orthopedic disorders were the most frequent reason for admission to hospital accounting for 57.8% of the study cohort, followed by cardiovascular disease with 15.6%. 51.1% of patients reported moderate to severe fatigue. Patients with and without fatigue were similar regarding age, sex, BMI, number of comorbidities and reason for admission. Fatigue score was correlated with higher functional
Discussion
The pathophysiology of fatigue in older adults is not yet fully understood. To our knowledge, this is the first study investigating mitochondrial respiration in PBMCs of older patients with fatigue in comparison to patients without fatigue.
A recent study by Tomas et al. likewise showed lower mitochondrial respiration in PBMCs of younger patients with chronic fatigue syndrome compared to control subjects (24–58 years) (Tomas et al., 2020), which prompted them to propose that PBMCs of patients
Funding
This work was supported by the Focus Area DynAge “Disease in Human Aging” (5.1.: 07/2016 - 06/2017) a collaboration of the Charité - Universitätsmedizin Berlin, the German Institute of Human Nutrition Potsdam - Rehbrücke, the Freie Universität Berlin and the Robert Koch Institute.
CRediT authorship contribution statement
Catrin Herpich: Investigation, formal analysis, Writing - Original Draft, Kristina Franz: Investigation, Writing - Review & Editing, Susanne Klaus: Conceptualization, Writing - Review & Editing, Ursula Müller-Werdan: Conceptualization, Writing - Review & Editing, Mario Ost: investigation, formal analysis, conceptualization, Kristina Norman: Conceptualization, Writing - Original Draft.
All authors commented on previous versions of the manuscript and approved the final manuscript.
Declaration of competing interest
None.
References (24)
The epidemiology of self-perceived fatigue among adults
Prev. Med.
(1986)- et al.
Association of Mitochondrial Dysfunction and Fatigue: a review of the literature
BBA Clin.
(2014) - et al.
Higher serum levels of fibroblast growth factor 21 in old patients with cachexia
Nutrition
(2019) - et al.
A review of the mitochondrial and glycolytic metabolism in human platelets and leukocytes: implications for their use as bioenergetic biomarkers
Redox Biol.
(2014) - et al.
Regulation of nutrition-associated receptors in blood monocytes of normal weight and obese humans
Peptides
(2015) - et al.
Validation of the German version of the brief fatigue inventory
J. Pain Symptom Manag.
(2003) - et al.
Mitochondrial dynamics: coupling mitochondrial fitness with healthy aging
Trends Mol. Med.
(2017) - et al.
Psychometric properties of the Brief Fatigue Inventory in community-dwelling older adults
Arch. Phys. Med. Rehabil.
(2014) - et al.
The mitochondrial basis of aging
Mol. Cell
(2016) - et al.
Blood-cell bioenergetics are associated with physical function and inflammation in overweight/obese older adults
Exp. Gerontol.
(2015)
Fatigue: relevance and implications in the aging population
Exp. Gerontol.
Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis
Nat. Immunol.
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2022, MitochondrionCitation Excerpt :Basal respiration and proton leak were not affected, suggesting that maximal respiration and spare capacity may be the bioenergetic parameters that are most sensitive to reduced sleep efficiency, which is consistent with our results. The association of sleep efficiency with maximal respiration was similar in magnitude to the previously observed association between maximal respiration and fatigue-related vitality (inverse) (Herpich et al., 2021), but smaller than for the inflammatory cytokine interleukin-6 (IL-6; inverse), grip strength, and a composite measure of physical function (positive) (Tyrrell et al., 2015). In humans, lower actigraphy-assessed sleep efficiency was associated with reduced urinary 8-hydroxydeoxyguanosine, an indicator of elevated oxidative DNA damage (Dranka et al., 2011), and with elevated circulating levels IL-6 (Nowakowski et al., 2018), which is associated with reduced maximal respiration and spare capacity in PBMCs (Tyrrell et al., 2015).
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These authors contributed equally to this work as senior authors.