Sex-associated differences in mitochondrial function in human peripheral blood mononuclear cells (PBMCs) and brain

Background: Alzheimer’s disease (AD) is the most common form of dementia, and it affects more women than men. Mitochondrial dysfunction (MD) plays a key role in AD, and it is detectable at an early stage of the degenerative process in peripheral tissues, such as peripheral mononuclear blood cells (PBMCs). However, whether these changes are also reflected in cerebral energy metabolism and whether sex-specific differences in mitochondrial function occur are not clear. Therefore, we estimated the correlation between mitochondrial function in PBMCs and brain energy metabolites and examined sex-specific differences in healthy participants to elucidate these issues. Methods: The current pilot study included 9 male and 15 female healthy adults (mean age 30.8 ± 7.1 years). Respiration and activity of mitochondrial respiratory complexes were measured using a Clarke-electrode (Oxygraph-2k system), and adenosine triphosphate (ATP) levels were determined using a bioluminescence-based assay in isolated PBMCs. Citrate synthase activity as a mitochondrial marker was measured using a photometric assay. Concentrations of brain energy metabolites were quantified in the same individuals using 1H-magnetic resonance spectroscopy (MRS). Results: We detected sex-associated differences in mitochondrial function. Mitochondrial complexes I, I+II, and IV and uncoupled respiration and electron transport system (ETS) capacity in PBMCs isolated from blood samples of females were significantly (p  50%) of gray matter (GM) (p < 0.05; p < 0.01). The effect sizes indicated a strong influence of sex on these parameters. Sex-associated differences were found in PBMCs and brain, but the determined parameters were not significantly correlated. Conclusions: Our study revealed sex-associated differences in mitochondrial function in healthy participants. The underlying mechanisms must be elucidated in more detail, but our study suggests that mitochondrial function in PBMCs is a feasible surrogate marker to detect differences in mitochondrial function and energy metabolism in humans and it underscores the necessity of sex-specific approaches in therapies that target mitochondrial dysfunction

Effects of aerobic exercise on brain metabolism and grey matter volume in older adults: results of the randomized controlled SMART trial

Matura S, Fleckenstein J, Deichmann R, et al. Effects of aerobic exercise on brain metabolism and grey matter volume in older adults: results of the randomized controlled SMART trial. Translational Psychiatry. 2017;7(7): e1172

Lifespan leisure activity profile and its relation to brain metabolism in the elderly

Engeroff T, Vogt L, Fleckenstein J, et al. Lifespan leisure activity profile and its relation to brain metabolism in the elderly. Acta Physiologica. 2016;216(S707):85-232

Metabolic changes upon supervised aerobic exercise in old adults monitored with 1H MRSI

Pilatus U, Lienerth B, Dietz K, et al. Metabolic changes upon supervised aerobic exercise in old adults monitored with 1H MRSI. Presented at the ISMRM 24th Annual Meeting and Exhibition, Singapore