Peripheral Blood Cells From Older Adults Exhibit Sex-Associated Differences in Mitochondrial Function

Abstract

Blood-based mitochondrial bioenergetic profiling is a feasible, economical, and minimally invasive approach that can be used to examine mitochondrial function and energy metabolism in human subjects. In this study, we use 2 complementary respirometric techniques to evaluate mitochondrial bioenergetics in both intact and permeabilized peripheral blood mononuclear cells (PBMCs) and platelets to examine sex dimorphism in mitochondrial function among older adults. Employing equal numbers of PBMCs and platelets to assess mitochondrial bioenergetics, we observe significantly higher respiration rates in female compared to male participants. Mitochondrial bioenergetic differences remain significant after controlling for independent parameters including demographic parameters (age, years of education), and cognitive parameters (mPACC5, COGDX). Our study illustrates that circulating blood cells, immune cells in particular, have distinctly different mitochondrial bioenergetic profiles between females and males. These differences should be taken into account as blood-based bioenergetic profiling is now commonly used to understand the role of mitochondrial bioenergetics in human health and aging.

Keywords: Lymphocytes; Mitochondrial bioenergetics; Neutrophils, Peripheral blood mononuclear cells; Platelets; Sex differences.

Graphical Abstract

Figure 1.

PBMCs from female participants show higher mitochondrial bioenergetic capacities than male participants. Intact PBMC mitochondrial respiration, measured as oxygen consumption rate (OCR; pmol min⁻¹ 250 000⁻¹ PBMCs), show that basal, maximal, spare respiratory capacities (SRC), and ATP-linked respiration are significantly higher in females than males (A–D). Permeabilized PBMC respiration mediated by fatty acid oxidation (FAO), measured as oxygen flux (pmol s⁻¹ 2 million⁻¹ PBMCs), show that FAO + CI + CII, MaxOXPHOS, and MaxETS respiration are significantly higher in females than males (E and F). Values are Mean ± Standard Deviation. p values ≤.05 are shown.