Moderate aerobic exercise training ameliorates impairment of mitochondrial function and dynamics in skeletal muscle of high-fat diet-induced obese mice.

The purpose of this study is to determine whether moderate aerobic exercise training improves high-fat diet-induced alterations in mitochondrial function and structure in the skeletal muscle. Male 4-week-old C57BL/6 mice were randomly divided into four groups: control (CON), control plus exercise (CON + EX), high-fat diet (HFD), and high-fat diet plus exercise (HFD + EX). After obesity was induced by 20 weeks of 60% HFD, treadmill exercise training was performed at 13-16 m/min, 40-50 min/day, and 6 days/week for 12 weeks. Mitochondrial structure, function, and dynamics, and mitophagy were analyzed in the skeletal muscle fibers from the red gastrocnemius. Exercise training increased mitochondrial number and area and reduced high-fat diet-induced obesity and hyperglycemia. In addition, exercise training attenuated mitochondrial dysfunction in the permeabilized myofibers, indicating that HFD-induced decrease of mitochondrial O2 respiration and Ca2+ retention capacity and increase of mitochondrial H2 O2 emission were attenuated in the HFD + EX group compared to the HFD group. Exercise also ameliorated HFD-induced imbalance of mitochondrial fusion and fission, demonstrating that HFD-induced decrease in fusion protein levels was elevated, and increase in fission protein levels was reduced in the HFD + EX groups compared with the HFD group. Moreover, dysregulation of mitophagy induced by HFD was mitigated in the HFD + EX group, indicating a decrease in PINK1 protein level. Our findings demonstrated that moderate aerobic exercise training mitigated obesity-induced insulin resistance by improving mitochondrial function, and reversed obesity-induced mitochondrial structural damage by improving mitochondrial dynamics and mitophagy, suggesting that moderate aerobic exercise training may play a therapeutic role in protecting the skeletal muscle against mitochondrial impairments and insulin resistance induced by obesity.

The immune modulatory effects of mitochondrial transplantation on cecal slurry model in rat.

BACKGROUND: Sepsis has a high mortality rate, but no specific drug has been proven effective, prompting the development of new drugs. Immunologically, sepsis can involve hyperinflammation, immune paralysis, or both, which might pose challenges during drug development. Recently, mitochondrial transplantation has emerged as a treatment modality for various diseases involving mitochondrial dysfunction, but it has never been tested for sepsis. METHODS: We isolated mitochondria from L6 muscle cells and umbilical cord mesenchymal stem cells and tested the quality of the isolated mitochondria. We conducted both in vivo and in vitro sepsis studies. We investigated the effects of intravenous mitochondrial transplantation on cecal slurry model in rats in terms of survival rate, bacterial clearance rate, and the immune response. Furthermore, we observed the effects of mitochondrial transplantation on the immune reaction regarding both hyperinflammation and immune paralysis. To do this, we studied early- and late-phase cytokine production in spleens from cecal slurry model in rats. We also used a lipopolysaccharide (LPS)-stimulated human PBMC monocyte model to confirm the immunological effects of mitochondrial transplantation. Apoptosis and the intrinsic apoptotic pathway were investigated in septic spleens. RESULTS: Mitochondrial transplantation improved survival and bacterial clearance. It also mitigated mitochondrial dysfunction and apoptosis in septic spleens and attenuated both hyperinflammation and immune paralysis in the spleens of cecal slurry model in rats. This effect was confirmed with an LPS-stimulated human PBMC study. CONCLUSIONS: In rat polymicrobial cecal slurry model, the outcome is improved by mitochondrial transplantation, which might have an immunomodulatory effect.

Effects of aging and exercise training on mitochondrial function and apoptosis in the rat heart.

Aging is associated with vulnerability to cardiovascular diseases, and mitochondrial dysfunction plays a critical role in cardiovascular disease pathogenesis. Exercise training is associated with benefits against chronic cardiac diseases. The purpose of this study was to determine the effects of aging and treadmill exercise training on mitochondrial function and apoptosis in the rat heart. Fischer 344 rats were divided into young sedentary (YS; n = 10, 4 months), young exercise (YE; n = 10, 4 months), old sedentary (OS; n = 10, 20 months), and old exercise (OE; n = 10, 20 months) groups. Exercise training groups ran on a treadmill at 15 m/min (young) or 10 m/min (old), 45 min/day, 5 days/week for 8 weeks. Morphological parameters, mitochondrial function, mitochondrial dynamics, mitophagy, and mitochondria-mediated apoptosis were analyzed in cardiac muscle. Mitochondrial O2 respiratory capacity and Ca2+ retention capacity gradually decreased, and mitochondrial H2O2 emitting potential significantly increased with aging. Exercise training attenuated aging-induced mitochondrial H2O2 emitting potential and mitochondrial O2 respiratory capacity, while protecting Ca2+ retention in the old groups. Aging triggered imbalanced mitochondrial dynamics and excess mitophagy, while exercise training ameliorated the aging-induced imbalance in mitochondrial dynamics and excess mitophagy. Aging induced increase in Bax and cleaved caspase-3 protein levels, while decreasing Bcl-2 levels. Exercise training protected against the elevation of apoptotic signaling markers by decreasing Bax and cleaved caspase-3 and increasing Bcl-2 protein levels, while decreasing the Bax/Bcl-2 ratio and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive myonuclei. These data demonstrate that regular exercise training prevents aging-induced impairment of mitochondrial function and mitochondria-mediated apoptosis in cardiac muscles.

Cardiac adaptation to exercise training in health and disease.

The heart is the primary pump that circulates blood through the entire cardiovascular system, serving many important functions in the body. Exercise training provides favorable anatomical and physiological changes that reduce the risk of heart disease and failure. Compared with pathological cardiac hypertrophy, exercise-induced physiological cardiac hypertrophy leads to an improvement in heart function. Exercise-induced cardiac remodeling is associated with gene regulatory mechanisms and cellular signaling pathways underlying cellular, molecular, and metabolic adaptations. Exercise training also promotes mitochondrial biogenesis and oxidative capacity leading to a decrease in cardiovascular disease. In this review, we summarized the exercise-induced adaptation in cardiac structure and function to understand cellular and molecular signaling pathways and mechanisms in preclinical and clinical trials.

Re-Setting the Circadian Clock Using Exercise against Sarcopenia.

Sarcopenia is defined as the involuntary loss of skeletal muscle mass and function with aging and is associated with several adverse health outcomes. Recently, the disruption of regular circadian rhythms, due to shift work or nocturnal lifestyle, is emerging as a novel deleterious factor for the development of sarcopenia. The underlying mechanisms responsible for circadian disruption-induced sarcopenia include molecular circadian clock and mitochondrial function associated with the regulation of circadian rhythms. Exercise is a potent modulator of skeletal muscle metabolism and is considered to be a crucial preventative and therapeutic intervention strategy for sarcopenia. Moreover, emerging evidence shows that exercise, acting as a zeitgeber (time cue) of the skeletal muscle clock, can be an efficacious tool for re-setting the clock in sarcopenia. In this review, we provide the evidence of the impact of circadian disruption on skeletal muscle loss resulting in sarcopenia. Furthermore, we highlight the importance of exercise timing (i.e., scheduled physical activity) as a novel therapeutic strategy to target circadian disruption in skeletal muscle.

Ursolic acid in health and disease.

Ursolic acid (UA) is a natural triterpene compound found in various fruits and vegetables. There is a growing interest in UA because of its beneficial effects, which include anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-carcinogenic effects. It exerts these effects in various tissues and organs: by suppressing nuclear factor-kappa B signaling in cancer cells, improving insulin signaling in adipose tissues, reducing the expression of markers of cardiac damage in the heart, decreasing inflammation and increasing the level of anti-oxidants in the brain, reducing apoptotic signaling and the level of oxidants in the liver, and reducing atrophy and increasing the expression levels of adenosine monophosphate-activated protein kinase and irisin in skeletal muscles. Moreover, UA can be used as an alternative medicine for the treatment and prevention of cancer, obesity/diabetes, cardiovascular disease, brain disease, liver disease, and muscle wasting (sarcopenia). In this review, we have summarized recent data on the beneficial effects and possible uses of UA in health and disease managements.

Effects of exercise on obesity-induced mitochondrial dysfunction in skeletal muscle.

Obesity is known to induce inhibition of glucose uptake, reduction of lipid metabolism, and progressive loss of skeletal muscle function, which are all associated with mitochondrial dysfunction in skeletal muscle. Mitochondria are dynamic organelles that regulate cellular metabolism and bioenergetics, including ATP production via oxidative phosphorylation. Due to these critical roles of mitochondria, mitochondrial dysfunction results in various diseases such as obesity and type 2 diabetes. Obesity is associated with impairment of mitochondrial function (e.g., decrease in O2 respiration and increase in oxidative stress) in skeletal muscle. The balance between mitochondrial fusion and fission is critical to maintain mitochondrial homeostasis in skeletal muscle. Obesity impairs mitochondrial dynamics, leading to an unbalance between fusion and fission by favorably shifting fission or reducing fusion proteins. Mitophagy is the catabolic process of damaged or unnecessary mitochondria. Obesity reduces mitochondrial biogenesis in skeletal muscle and increases accumulation of dysfunctional cellular organelles, suggesting that mitophagy does not work properly in obesity. Mitochondrial dysfunction and oxidative stress are reported to trigger apoptosis, and mitochondrial apoptosis is induced by obesity in skeletal muscle. It is well known that exercise is the most effective intervention to protect against obesity. Although the cellular and molecular mechanisms by which exercise protects against obesity-induced mitochondrial dysfunction in skeletal muscle are not clearly elucidated, exercise training attenuates mitochondrial dysfunction, allows mitochondria to maintain the balance between mitochondrial dynamics and mitophagy, and reduces apoptotic signaling in obese skeletal muscle.

Low-intensity treadmill exercise protects cognitive impairment by enhancing cerebellar mitochondrial calcium retention capacity in a rat model of chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion (CCH) is caused by reduced blood flow to the brain representing gradually cognitive impairment. CCH induces mitochondrial dysfunction and neuronal cell death in the brain. Exercise is known to have a neuroprotective effect on brain damage and cognitive dysfunction. This study aimed to clarify the neuroprotective effect of low-intensity treadmill exercise (LITE) by enhancing cerebellar mitochondrial calcium retention capacity in an animal model of CCH. Wistar rats were divided into the sham group, the bilateral common carotid arteries occlusion (BCCAO) group, and the BCCAO and treadmill exercise (BCCAO+Ex) group. BCCAO+Ex group engaged the LITE on a treadmill for 30 min once a day for 8 weeks before the BCCAO surgery to investigate the protective effect of LITE on cognitive impairment. CCH induced by BCCAO resulted in mitochondrial dysfunction in the cerebellum, including impaired calcium homeostasis. CCH also decreased cerebellar Purkinje cells including of calbindin D28k and parvalbumin, resulting in cognitive impairment. The impairment of mitochondrial function, loss of cerebellar Purkinje cells, and cognitive dysfunction ameliorated by exercise. The present study showed that LITE hindered the deficit of spatial working memory and loss of Purkinje cell in the cerebellum induced by CCH. We confirmed that the protective effect of LITE on Purkinje cell by enhanced the mitochondrial calcium retention capacity. We suggest that LITE may protect against cognitive impairment, and further studies are needed to develop the intervention for patients who suffered from CCH.

Sexually Dimorphic Effects of a Western Diet on Brain Mitochondrial Bioenergetics and Neurocognitive Function.

A Western diet (WD), high in sugars and saturated fats, impairs learning and memory function and contributes to weight gain. Mitochondria in the brain provide energy for neurocognitive function and may play a role in body weight regulation. We sought to determine whether a WD alters behavior and metabolic outcomes in male and female rodents through impacting hippocampal and hypothalamic mitochondrial bioenergetics. Results revealed a sexually dimorphic macronutrient preference, where males on the WD consumed a greater percentage of calories from fat/protein and females consumed a greater percentage of calories from a sugar-sweetened beverage. Both males and females on a WD gained body fat and showed impaired glucose tolerance when compared to same-sex controls. Males on a WD demonstrated impaired hippocampal functioning and an elevated tendency toward a high membrane potential in hippocampal mitochondria. Comprehensive bioenergetics analysis of WD effects in the hypothalamus revealed a tissue-specific adaption, where males on the WD oxidized more fat, and females oxidized more fat and carbohydrates at peak energy demand compared to same-sex controls. These results suggest that adult male rats show a susceptibility toward hippocampal dysfunction on a WD, and that hypothalamic mitochondrial bioenergetics are altered by WD in a sex-specific manner.

Effects of cisplatin on mitochondrial function and autophagy-related proteins in skeletal muscle of rats.

Cisplatin is widely known as an anti-cancer drug. However, the effects of cisplatin on mitochondrial function and autophagyrelated proteins levels in the skeletal muscle are unclear. The purpose of this study was to investigate the effect of different doses of cisplatin on mitochondrial function and autophagy-related protein levels in the skeletal muscle of rats. Eight-weekold male Wistar rats (n = 24) were assigned to one of three groups; the first group was administered a saline placebo (CON, n = 10), and the second and third groups were given 0.1 mg/kg body weight (BW) (n = 6), and 0.5 mg/kg BW (n = 8) of cisplatin, respectively. The group that had been administered 0.5 mg cisplatin exhibited a reduced BW, skeletal muscle tissue weight, and mitochondrial function and upregulated levels of autophagy-related proteins, including LC3II, Beclin 1, and BNIP3. Moreover, this group had a high LC3 II/I ratio in the skeletal muscle; i.e., the administration of a high dose of cisplatin decreased the muscle mass and mitochondrial function and increased the levels of autophagy-related proteins. These results, thus, suggest that reducing mitochondrial dysfunction and autophagy pathways may be important for preventing skeletal muscle atrophy following cisplatin administration. [BMB Reports 2021; 54(11): 575-580].

Exercise as a Therapeutic Strategy for Sarcopenia in Heart Failure: Insights into Underlying Mechanisms.

Sarcopenia, a syndrome commonly seen in elderly populations, is often characterized by a gradual loss of skeletal muscle, leading to the decline of muscle strength and physical performance. Growing evidence suggests that the prevalence of sarcopenia increases in patients with heart failure (HF), which is a dominant pathogenesis in the aging heart. HF causes diverse metabolic complications that may result in sarcopenia. Therefore, sarcopenia may act as a strong predictor of frailty, disability, and mortality associated with HF. Currently, standard treatments for slowing muscle loss in patients with HF are not available. Therefore, here, we review the pathophysiological mechanisms underlying sarcopenia in HF as well as current knowledge regarding the beneficial effects of exercise on sarcopenia in HF and related mechanisms, including hormonal changes, myostatin, oxidative stress, inflammation, apoptosis, autophagy, the ubiquitin-proteasome system, and insulin resistance.

Aging Promotes Mitochondria-Mediated Apoptosis in Rat Hearts.

Aging represents a major risk for developing cardiac disease, including heart failure. The gradual deterioration of cell quality control with aging leads to cell death, a phenomenon associated with mitochondrial dysfunction in the heart. Apoptosis is an important quality control process and a necessary phenomenon for maintaining homeostasis and normal function of the heart. However, the mechanism of mitochondria-mediated apoptosis in aged hearts remains poorly understood. Here, we used male Fischer 344 rats of various ages, representing very young (1 month), young (4 months), middle-aged (12 months), and old (20 months) rats, to determine whether mitochondria-mediated apoptotic signals and apoptosis in the left ventricle of the heart are altered notably with aging. As the rats aged, the extramyocyte space and myocyte cross-sectional area in their left ventricle muscle increased, while the number of myocytes decreased. Additionally, mitochondrion-mediated apoptotic signals and apoptosis increased remarkably during aging. Therefore, our results demonstrate that aging promotes remarkable morphological changes and increases the degree of mitochondrion-mediated apoptosis in the left ventricle of rat hearts.

Exercise Training Protects against Atorvastatin-Induced Skeletal Muscle Dysfunction and Mitochondrial Dysfunction in the Skeletal Muscle of Rats.

Statins are used to prevent and treat atherosclerotic cardiovascular disease, but they also induce myopathy and mitochondrial dysfunction. Here, we investigated whether exercise training prevents glucose intolerance, muscle impairment, and mitochondrial dysfunction in the skeletal muscles of Wistar rats treated with atorvastatin (5 mg kg-1 day-1) for 12 weeks. The rats were assigned to the following three groups: the control (CON), atorvastatin-treated (ATO), and ATO plus aerobic exercise training groups (ATO+EXE). The ATO+EXE group exhibited higher glucose tolerance and forelimb strength and lower creatine kinase levels than the other groups. Mitochondrial respiratory and Ca2+ retention capacity was significantly lower in the ATO group than in the other groups, but exercise training protected against atorvastatin-induced impairment in both the soleus and white gastrocnemius muscles. The mitochondrial H2O2 emission rate was relatively higher in the ATO group and lower in the ATO+EXE group, in both the soleus and white gastrocnemius muscles, than in the CON group. In the soleus muscle, the Bcl-2, SOD1, SOD2, Akt, and AMPK phosphorylation levels were significantly higher in the ATO+EXE group than in the ATO group. In the white gastrocnemius muscle, the SOD2, Akt, and AMPK phosphorylation levels were significantly higher in the ATO+EXE group than in the ATO group. Therefore, exercise training might regulate atorvastatin-induced muscle damage, muscle fatigue, and mitochondrial dysfunction in the skeletal muscles.

Exercise and Neuroinflammation in Health and Disease.

Neuroinflammation is a central pathological feature of several acute and chronic brain diseases, including Alzheimer disease (AD), Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). It induces microglia activation, mitochondrial dysfunction, the production of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), pro-inflammatory cytokines, and reactive oxygen species. Exercise, which plays an important role in maintaining and improving brain health, might be a highly effective intervention for preventing neuroinflammation-related diseases. Thus, since exercise can improve the neuroimmune response, we hypothesized that exercise would attenuate neuroinflammation-related diseases. In this review, we will highlight (1) the biological mechanisms that underlie AD, PD, ALS, and MS, including the neuroinflammation pathways associated with microglia activation, NF-κB, pro-inflammatory cytokines, mitochondrial dysfunction, and reactive oxygen species, and (2) the role of exercise in neuroinflammation-related neurodegenerative diseases.

Effects of a single bout of exercise on mitochondria-mediated apoptotic signaling in rat cardiac and skeletal muscles.

This study aimed to determine the effects of a single bout exercise on mitochondria-mediated apoptotic signaling in cardiac and skeletal muscles. Fischer 344 rats (4 months old) were randomly divided into the control or a single bout of exercise group (n=10 each). The rats performed a single bout of treadmill exercise for 60 min. Mitochondria-mediated apoptotic signaling (e.g., Bax, Bcl-2, mitochondrial permeability transition pore [mPTP] opening, cytochrome c, and cleaved caspase-3) was measured in cardiac (e.g., left ventricle) and skeletal (e.g., soleus and white gastrocnemius) muscles. A single bout of exercise significantly decreased mPTP opening sensitivity in all tissues. However, a single bout of exercise did not show any statistical differences in Bax, Bcl-2, cytochrome c, and cleaved caspase-3 in all tissues measured. A single bout of exercise did not show definite results on characteristics of mitochondria-mediated apoptotic signaling. Therefore, further research is necessary to provide a more mechanistic understanding of the apoptosis pathway.

Effects of Acute Exercise on Mitochondrial Function, Dynamics, and Mitophagy in Rat Cardiac and Skeletal Muscles.

PURPOSE: This study aimed to investigate the effects of single-bout exercise on mitochondrial function, dynamics (fusion, fission), and mitophagy in cardiac and skeletal muscles. METHODS: Fischer 344 rats (4 months old) were randomly divided into the control (CON) or acute exercise (EX) group (n=10 each). The rats performed a single bout of treadmill exercise for 60 minutes. Mitochondrial function (e.g., O2 respiration, H2O2 emission, Ca2+ retention capacity), mitochondrial fusion (e.g., Mfn1, Mfn2, Opa1), mitochondrial fission (e.g., Drp1, Fis1), and mitophagy (e.g., Parkin, Pink1, LC3II, Bnip3) were measured in permeabilized cardiac (e.g., left ventricle) and skeletal (e.g., soleus, white gastrocnemius) muscles. RESULTS: Mitochondrial O2 respiration and Ca2+ retention capacity were significantly increased in all tissues of the EX group compared with the CON group. Mitochondrial H2O2 emissions showed tissue-specific results; the emissions showed no significant differences in the left ventricle or soleus (type I fibers) but was significantly increased in the white gastrocnemius (type II fibers) after acute exercise. Mitochondrial fusion and fission were not altered in any tissues of the EX group. Mitophagy showed tissue-specific differences: It was not changed in the left ventricle or white gastrocnemius, whereas Parkin and LC3II were significantly elevated in the soleus muscle. CONCLUSION: A single bout of aerobic exercise may improve mitochondrial function (e.g., O2 respiration and Ca2+ retention capacity) in the heart and skeletal muscles without changes in mitochondrial dynamics or mitophagy.

Treadmill Exercise Ameliorates Chemotherapy-Induced Muscle Weakness and Central Fatigue by Enhancing Mitochondrial Function and Inhibiting Apoptosis.

PURPOSE: Chemotherapy is associated with the side effects including damage to the mitochondrial DNA. Doxorubicin (DOX) serves as a chemotherapeutic agent for the patients with breast cancer or prostate cancer. DOX causes muscle weakness and fatigue. We investigated the effects of treadmill exercise on DOX-induced apoptosis and mitochondrial dysfunction in relation to central fatigue. For this study, we used the rat model of DOX-induced muscle damage. METHODS: DOX (2 mg/kg) was intraperitoneally injected 1 time per week for 4 weeks. Treadmill running continued 5 days per week for 4 weeks. Muscle strength and fatigue index in the gastrocnemius were measured. Immunohistochemistry for the expressions of tryptophan hydroxylase (TPH) and 5-hydroxytryptamine (5-HT) in the dorsal raphe was conducted. We used western blot analysis for the expressions of Bax, Bcl-2, and caspases-3 in the gastrocnemius. Mitochondrial function in the gastrocnemius was also evaluated. RESULTS: DOX treatment decreased muscle strength with increase of fatigue index in the gastrocnemius. Mitochondria function was deteriorated and apoptosis in the gastrocnemius was enhanced by DOX treatment. Expressions of TPH and 5-HT in the dorsal raphe were increased by DOX treatment. Treadmill exercise attenuated DOX-induced muscle fatigue and impairment of mitochondria function. Apoptosis in the gastrocnemius was inhibited and over-expression of TPH and 5-HT was suppressed by treadmill exercise. CONCLUSION: Apoptosis was enhanced and mitochondria function was deteriorated by DOX treatment, resulting in muscle weakness and central fatigue. Treadmill exercise suppressed apoptosis and prevented deterioration of mitochondria function in muscle, resulting in alleviation of muscle weakness and central fatigue during DOX therapy.

Physical exercise prevents cognitive impairment by enhancing hippocampal neuroplasticity and mitochondrial function in doxorubicin-induced chemobrain.

Although chemotherapy increases the survival rate of patients with various cancers, such treatment can induce acute or long-term cognitive dysfunction a phenomenon known as post-chemotherapy cognitive impairment (PCCI) or "chemobrain." Exercise is known to positively affect brain function. Thus, the present study aimed to determine whether symptoms of chemobrain and disruptions in the neuroplasticity and functioning of hippocampal mitochondria can be prevented or relieved by exercise. Wistar rats were separated into the following groups: control, control plus exercise, chemobrain, and chemobrain plus exercise. For chemobrain induction, 2 mg/kg of doxorubicin (DOX) a widely utilized chemotherapeutic agent among patients with breast cancer was dissolved in saline and directly injected to the abdomen once every 4 weeks. The exercise groups were subjected to low-intensity treadmill, 6 days per week for 4 weeks. The Morris water maze and step-down avoidance tests were conducted to evaluate cognitive function, while neuroplasticity and mitochondrial function were assessed in the hippocampus and dentate gyrus. Decreased cognitive function were observed in the chemobrain group, along with decreases in levels of neurogenesis, brain derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), Ca2+ retention in hippocampus. Rats of the chemobrain group also exhibited an increase in apoptosis, H2O2 emission and permeability transition pore by hippocampal mitochondria. However, exercise attenuated impairments in cognitive function, neuroplasticity, and mitochondrial function induced by DOX treatment. Therefore, the findings of the present study indicate that low-intensity exercise may assist in preventing cognitive dysfunction during or after chemotherapy in patients with various cancers, including breast cancer.

Role of exercise in age-related sarcopenia.

Sarcopenia is an age-associated decline of skeletal muscle mass and function and is known to lead to frailty, cachexia, osteoporosis, metabolic syndromes, and death. Notwithstanding the increasing incidence of sarcopenia, the molecular and cellular mechanisms driving age-related sarcopenia are not completely understood. This article reviews current definitions of sarcopenia, its potential mechanisms, and effects of exercise on sarcopenia. The pathogenesis of age-related sarcopenia is multifactorial and includes myostatin, inflammatory cytokines, and mitochondria-derived problems. Especially, age-induced mitochondrial dysfunction triggers the production of reactive oxygen species (ROS) by mitochondria, impedes mitochondrial dynamics, interrupts mitophagy, and leads to mitochondria-mediated apoptosis. Aerobic exercise provides at least a partial solution to sarcopenia as it ameliorates mitochondria-derived problems, and resistance exercise strengthens muscle mass and function. Furthermore, combinations of these exercise types provide the benefits of both. Collectively, this review summarizes potential mechanisms of age-related sarcopenia and emphasizes the use of exercise as a therapeutic strategy, suggesting that combined exercise provides the most beneficial means of combating age-related sarcopenia.

Effects of aging on mitochondrial hydrogen peroxide emission and calcium retention capacity in rat heart.

Aging is a risk factor for heart disease and heart failure, which result from a progressive impairment of cardiac functions, including stroke volume, cardiac output, blood flow, and oxygen consumption. Age-related cardiac dysfunction is associated with impaired cardiac structures, such as the loss of myocytes, structural remodeling, altered calcium (Ca2+) handling, and contractile dysfunction. However, the mechanism by which aging affects mitochondrial function in the heart is poorly understood. The purpose of this study was to determine the effects of aging on mitochondrial function in the rat heart. Male Fischer 344 rats were randomly assigned to very young sedentary (VYS, 1 month), young sedentary (YS, 4 months), middle-aged sedentary (MS, 10 months), and old sedentary (OS, 20 months) groups. mitochondrial complex protein levels and mitochondrial function (e.g., mitochondrial hydrogen peroxide (H2O2) emission and Ca2+ retention capacity) were analyzed in the left ventricle. Aging was associated with decreased levels of OXPHOS (oxidative phosphorylation) protein expression of complex I to IV in the function of the electron transport chain. Aging increased the mitochondrial H2O2 emitting potential in the heart. In contrast, mitochondrial Ca2+ retention capacity gradually decreased with age. These data demonstrate that aging impairs mitochondrial function in cardiac muscle, suggesting that mitochondrial dysfunction with aging may be a primary factor for aging-induced cardiac dysfunction in the heart.