For instance, the reduction of the cytosolic antioxidant CuZn-superoxide dismutase (CuZnSOD) was observed in mouse nerves and muscle, consistent with sarcopenic muscle loss (47). The activation of apoptotic signals is accompanied by DNA fragmentation and subsequent nuclear apoptosis, which eventually leads to muscle atrophy and denervation. Interestingly, circulating levels of mtDNA rise gradually with age and connect with those of systemic pro-inflammatory cytokines, such as interleukin 6 (IL6) and tumor necrosis factor-alpha (TNF-α) (44). Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), quinone oxidoreductase 1 (NQO1), and heme oxygenase 1 (HO-1) are enzymes that constitute the key to the cellular antioxidant defense system. The ETC consists of five protein complexes forming a redox chain (also known as the respiratory chain). The common factor between these studies is the interaction of estrogen within the nucleus and mitochondria. Estrus cycle-dependent differences have been previously reported in various aspects of the neuron, from electrophysiological mini excitatory postsynaptic currents (Proaño et al., 2020) to alterations in the production of transcription factors within the medial prefrontal cortex of rodents (Duclot and Kabbaj, 2015). Studies linking MitoQ to estrogen within the brain are limited, yet a study assessing GPER-mediated cardiac function suggests a connection exists. The mitoceutical MitoQ, a compound based on coenzyme Q10 (CoQ10), is an antioxidant specifically targeted to the mitochondria (Tauskela, 2007), with a number of studies completed in vitro and in vivo in both rodents and humans (Smith and Murphy, 2010). Transplantation of healthy mitochondria, in theory, may correct deficits in substrate utilization, yet more research needs to be conducted to reveal the root cause of this sex difference post TBI and if mitochondria can be transplanted from a donor of a different sex. Mitochondrial dysfunction has been documented following TBI (Fischer et al., 2016; Normoyle et al., 2015; Pietro et al., 2017) and appears to act in a sex-specific mechanism (Greco et al., 2020). Mitochondrial transplantation efforts have been utilized in rodent models of cardiac (Chernyak, 2020; Lim, 2020) and pulmonary ailments (Hsu et al., 2020; Li et al., 2014), with promising results in studies using a pulmonary hypertension model in adult rats (Hsu et al., 2020). The harvested cells were incubated in Rh123 solution (10 μg/mL, Sigma) at 37°C for 30 min, washed, resuspended in 1 mL PBS, and immediately analyzed by flow cytometry. MMP was estimated in dissociated SN/HIPP cells using Rhodamine 123 (Rh123) fluorescence. Mitochondrial complex activity was normalized to the total protein amount (μmol/min/g protein). The supernatant was centrifuged again at 3500 × g at 4°C for 10 min to harvest the mitochondrial pellet. For detection of enzymatic activities of mitochondrial complexes I, II, III, IV, and V, mitochondria were isolated from SN or HIPP tissue blocks using a Tissue Mitochondria Isolation Kit (Code C3606, Beyotime Institute of Biotechnology, China). The tissue block containing the SN or HIPP was dissected on an ice-cold plate under stereomicroscopy and immediately processed for assays of MDA, GSH, GSH-PX, Mn-SOD, MMP, and mitochondrial complexes activities, or snap-frozen in liquid nitrogen and stored at −80°C for qPCR and western blot assays. Sarcopenia is a skeletal muscle disorder characterized by progressive and generalized loss of muscle mass and strength/function upon aging, with an increased risk of adverse outcomes, including falls, disability, loss of independence, morbidity, and mortality (1). Although the exact mechanisms underlying sarcopenia are not fully understood, evidence suggests that the loss of mitochondrial integrity in skeletal myocytes has emerged as a pivotal contributor to the complex etiology of sarcopenia. Of relevance to this issue, in our laboratory we demonstrated that testosterone protects against oxidative stress-induced apoptosis in skeletal muscle 7-9. Testosterone supplementation increases muscle mass in healthy young and old men, healthy hypogonadal men and in other physiological or pathological conditions with low levels of this steroid . Managing stress is equally important; high-stress levels can impair mitochondrial function. Addressing mitochondrial health through proper nutrition and lifestyle choices supports testosterone production, enhancing physical and mental well-being. By prioritizing mitochondrial health through lifestyle choices, you can optimize testosterone levels and support your body’s hormonal balance.
