Relationships between human vitality and mitochondrial respiratory parameters, reactive oxygen species production and dNTP levels in peripheral blood mononuclear cells

Scott Maynard,Merete Osler,Guido Keijzers,Vilhelm A Bohr,Martin Gram,Deborah L Croteau,Laila Bendix,Tinna Stevnsner,Kirsten Avlund,Flemming Dela,Lene Juel Rasmussen,Esben Budtz-Jørgensen,Claus Desler,Drude Molbo

doi:10.18632/aging.100618

Abstract

Low vitality (a component of fatigue) in middle-aged and older adults is an important complaint often identified as a symptom of a disease state or side effect of a treatment. No studies to date have investigated the potential link between dysfunctional mitochondrial ATP production and low vitality. Therefore, we measured a number of cellular parameters related to mitochondrial activity in peripheral blood mononuclear cells (PBMCs) isolated from middle-aged men, and tested for association with vitality. These parameters estimate mitochondrial respiration, reactive oxygen species (ROS) production, and deoxyribonucleotide (dNTP) balance in PBMCs. The population was drawn from the Metropolit cohort of men born in 1953. Vitality level was estimated from the Medical Outcomes Study Short Form 36 (SF-36) vitality scale. We found that vitality score had no association with any of the mitochondrial respiration parameters. However, vitality score was inversely associated with cellular ROS production and cellular deoxythymidine triphosphate (dTTP) levels and positively associated with deoxycytidine triphosphate (dCTP) levels. We conclude that self-reported persistent low vitality is not associated with specific aspects of mitochondrial oxidative phosphorylation capacity in PBMCs, but may have other underlying cellular dysfunctions that contribute to dNTP imbalance and altered ROS production.

Highlights

The Medical Outcomes Study Short Form 36 (SF-36) vitality scale used in this study is a frequently cited and validated subscale or component of the multicomponent SF-36 fatigue scale
The two extracellular acidification rate (ECAR) parameters that we report here were chosen because they are the most informative with respect to the contribution of glycolysis to cellular energy production
None of the oxygen consumption rate (OCR) or ECAR parameters had a significant association with vitality score (Table 1: Figures S1 and S2)

Summary

Introduction

The Medical Outcomes Study Short Form 36 (SF-36) vitality scale used in this study is a frequently cited and validated subscale or component of the multicomponent SF-36 fatigue scale. There have been no studies to assess a potential role of defects in mitochondrial oxidative phosphorylation, or other mitochondrial-related defects, in human vitality. Towards this end, we measured several mitochondrialrelated cellular parameters in peripheral blood mononuclear cells (PBMCs) to assess potential associations of mitochondrial activities with vitality score. We measured several mitochondrialrelated cellular parameters in peripheral blood mononuclear cells (PBMCs) to assess potential associations of mitochondrial activities with vitality score Such analysis may give insight into mechanisms underlying low vitality or lead to biomarkers for diseases that have low vitality as a core symptom. PBMCs have been shown to be a suitable cell model for mitochondrial dysfunction and oxidative stress in biomarker discovery for Alzheimer’s disease, fibromyalgia and chronic fatigue syndrome [10,11,12]

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