Ketogenic diet with aerobic exercise can induce fat browning: potential roles of ß-hydroxybutyrate.

Introduction: Despite evidence suggesting that metabolic intermediates like ß-HB influence white adipose tissue (WAT) metabolism, the precise molecular mechanisms remain unclear. The aim of this study was to investigate the impact of beta-hydroxybutyrate (ß-HB) on the fat browning program and to explore the underlying molecular mechanisms using both in vitro and in vivo models. We assessed the effects of ß-HB on fat browning in adipocytes using 3T3-L1 cells and rat models. Methods: We evaluated the effects of ß-HB on fat browning, thermogenesis, lipid accumulation, adipokine expression, and mitochondrial biogenesis by treating mature 3T3-L1 adipocytes with sodium ß-HB for 24 h or by continuously exposing preadipocytes to ß-HB during the 8-day differentiation process. Male Sprague Dawley rats were divided into control, exercise only (EX), ketogenic diet only (KD), and combined exercise and ketogenic diet (KE) groups for an 8-week intervention involving diet and/or exercise. After intervention, we evaluated WAT histology, plasma lipids and adipokines, and the expression of markers related to fat browning, thermogenesis and mitochondrial biogenesis in WAT of rats. Results: In our adipocyte culture experiments, ß-HB reduced intracellular lipid accumulation by enhancing lipolysis and stimulated the expression of thermogenic and fat browning genes like uncoupling protein 1 (UCP1), PR domain containing 16 (PRDM16), and adipokines such as fibroblast growth factor 21 (FGF21) and Fibronectin type III domain-containing protein 5 (FDNC5). Additionally, ß-HB activated the AMPK-SIRT1-PGC-1α pathway, with UCP1 and PRDM16 upregulation mediated by ß-HB intracellular action and SIRT1 activity. In animal experiments, KE group raised ß-HB levels, decreasing body weight and blood lipids. KD with EX promoted WAT browning possibly via AMPK-SIRT1-PGC-1α, augmenting PRDM16, UCP1, FGF21, and FNDC5 expression. Conclusion: ß-HB induction via KD and/or EX shows potential in promoting WAT browning by activating mitochondrial biogenesis, lipolysis, and thermogenesis, suggesting that dietary and physical intervention inducing ß-HB may benefit metabolic health.

Mitochondrial Adaptations in Aging Skeletal Muscle: Implications for Resistance Exercise Training to Treat Sarcopenia.

Sarcopenia, the age-related decline in muscle mass and function, poses a significant health challenge as the global population ages. Mitochondrial dysfunction is a key factor in sarcopenia, as evidenced by the role of mitochondrial reactive oxygen species (mtROS) in mitochondrial biogenesis and dynamics, as well as mitophagy. Resistance exercise training (RET) is a well-established intervention for sarcopenia; however, its effects on the mitochondria in aging skeletal muscles remain unclear. This review aims to elucidate the relationship between mitochondrial dynamics and sarcopenia, with a specific focus on the implications of RET. Although aerobic exercise training (AET) has traditionally been viewed as more effective for mitochondrial enhancement, emerging evidence suggests that RET may also confer beneficial effects. Here, we highlight the potential of RET to modulate mtROS, drive mitochondrial biogenesis, optimize mitochondrial dynamics, and promote mitophagy in aging skeletal muscles. Understanding this interplay offers insights for combating sarcopenia and preserving skeletal muscle health in aging individuals.

Adolescent obesity and short sleep duration as independent risk factors for hypertension: a population-based cohort study.

Prevalence of hypertension in adolescents has increased worldwide and is considered a risk factor for hypertension and cardiovascular disease in adulthood. Although obesity and sleep deficiency increase this risk, the combined effects of these factors on hypertension remain unclear. This study aimed to examine the combined effects of obesity and sleep duration on hypertension in adolescents. This study was conducted using data from the 2016 to 2018 Korean National Health and Nutrition Examination Survey, which included a study population of 1272 adolescents. The participants were categorized into four groups based on sleep duration and body mass index (BMI) percentiles: normal sleep and normal body mass group (reference; normal), only short sleep group (short sleep), only overweight/obesity group (overweight/obesity), and short sleep and overweight/obesity group (short sleep and overweight/obesity). Short sleep duration was defined as <8 h of average sleep duration, and overweight/obesity was defined as a BMI ≥ 85th percentile. Hypertension in adolescents was defined as a systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg. The prevalence of hypertension was 9.2% among Korean adolescents. Short sleep duration with overweight/obesity were associated with a significantly increased risk of hypertension (odds ratio = 6.57; 95% confidence interval: 3.27-13.20) in adolescents, and controlling for the potential confounding variables only partially attenuated this relationship (odds ratio = 5.28; 95% confidence interval: 2.28-12.26). This study demonstrated that the coexistence of short sleep duration and obesity was associated with an increased risk of hypertension in Korean adolescents.

Free essential amino acid feeding improves endurance during resistance training via DRP1-dependent mitochondrial remodelling.

BACKGROUND: Loss of muscle strength and endurance with aging or in various conditions negatively affects quality of life. Resistance exercise training (RET) is the most powerful means to improve muscle mass and strength, but it does not generally lead to improvements in endurance capacity. Free essential amino acids (EAAs) act as precursors and stimuli for synthesis of both mitochondrial and myofibrillar proteins that could potentially confer endurance and strength gains. Thus, we hypothesized that daily consumption of a dietary supplement of nine free EAAs with RET improves endurance in addition to the strength gains by RET. METHODS: Male C57BL6J mice (9 weeks old) were assigned to control (CON), EAA, RET (ladder climbing, 3 times a week), or combined treatment of EAA and RET (EAA + RET) groups. Physical functions focusing on strength or endurance were assessed before and after the interventions. Several analyses were performed to gain better insight into the mechanisms by which muscle function was improved. We determined cumulative rates of myofibrillar and mitochondrial protein synthesis using 2H2O labelling and mass spectrometry; assessed ex vivo contractile properties and in vitro mitochondrial function, evaluated neuromuscular junction (NMJ) stability, and assessed implicated molecular singling pathways. Furthermore, whole-body and muscle insulin sensitivity along with glucose metabolism, were evaluated using a hyperinsulinaemic-euglycaemic clamp. RESULTS: EAA + RET increased muscle mass (10%, P < 0.05) and strength (6%, P < 0.05) more than RET alone, due to an enhanced rate of integrated muscle protein synthesis (19%, P < 0.05) with concomitant activation of Akt1/mTORC1 signalling. Muscle quality (muscle strength normalized to mass) was improved by RET (i.e., RET and EAA + RET) compared with sedentary groups (10%, P < 0.05), which was associated with increased AchR cluster size and MuSK activation (P < 0.05). EAA + RET also increased endurance capacity more than RET alone (26%, P < 0.05) by increasing both mitochondrial protein synthesis (53%, P < 0.05) and DRP1 activation (P < 0.05). Maximal respiratory capacity increased (P < 0.05) through activation of the mTORC1-DRP1 signalling axis. These favourable effects were accompanied by an improvement in basal glucose metabolism (i.e., blood glucose concentrations and endogenous glucose production vs. CON, P < 0.05). CONCLUSIONS: Combined treatment with balanced free EAAs and RET may effectively promote endurance capacity as well as muscle strength through increased muscle protein synthesis, improved NMJ stability, and enhanced mitochondrial dynamics via mTORC1-DRP1 axis activation, ultimately leading to improved basal glucose metabolism.

Protective effect of increased O-GlcNAc cycling against 6-OHDA induced Parkinson's disease pathology.

This study aimed to elucidate the role of O-GlcNAc cycling in 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD)-like neurodegeneration and the underlying mechanisms. We observed dose-dependent downregulation of O-GlcNAcylation, accompanied by an increase in O-GlcNAcase following 6-OHDA treatment in both mouse brain and Neuro2a cells. Interestingly, elevating O-GlcNAcylation through glucosamine (GlcN) injection provided protection against PD pathogenesis induced by 6-OHDA. At the behavioral level, GlcN mitigated motor deficits induced by 6-OHDA, as determined using the pole, cylinder, and apomorphine rotation tests. Furthermore, GlcN attenuated 6-OHDA-induced neuroinflammation and mitochondrial dysfunction. Notably, augmented O-GlcNAcylation, achieved through O-GlcNAc transferase (OGT) overexpression in mouse brain, conferred protection against 6-OHDA-induced PD pathology, encompassing neuronal cell death, motor deficits, neuroinflammation, and mitochondrial dysfunction. These collective findings suggest that O-GlcNAcylation plays a crucial role in the normal functioning of dopamine neurons. Moreover, enhancing O-GlcNAcylation through genetic and pharmacological means could effectively ameliorate neurodegeneration and motor impairment in an animal model of PD. These results propose a potential strategy for safeguarding against the deterioration of dopamine neurons implicated in PD pathogenesis.

Effects of physical activity participation on cognitive impairment in older adults population with disabilities.

Background: Existing research on the association between cognitive function and physical activity in the older adults population with disabilities is limited. Additionally, there is a need to explore avenues for enhancing the longevity and quality of life among these individuals. Objective: This study aimed to investigate the independent and joint associations between cognitive function and levels of physical activity in the older adults population with disabilities. Methods: A total of 315 older adults adults (men = 182, women = 133), identified with disabilities based on medical evaluation, were recruited from the first survey of the Korean Longitudinal Study of Aging (KLoSA). Participants underwent assessments for cognitive function, physical activity (PA), activities of daily living (ADLs), instrumental activities of daily living (IADLs), and grip strength. Results: ADLs (p < 0.001) and IADLs (p < 0.001) scores were significantly higher in the male normal cognitive group compared to both the male and female cognitive impairment groups. In an unadjusted model, disabled older adults individuals who did not meet the recommended PA guidelines showed an increased odds ratio for cognitive dysfunction (OR = 2.29, 95% CI = 1.32-3.97). Those participating in PA at least 1 day per week also demonstrated an elevated odds ratio (OR = 1.22, 95% CI = 1.08-1.38) for cognitive dysfunction compared to those who engaged in regular PA. A negative correlation was observed between K-MMSE scores and grip strength (r = 0.448, p < 0.001). Conclusion: This study provides robust evidence that disabled older adults individuals who do not meet the recommended guidelines for PA or who do not participate in PA at least once a week have an increased likelihood of cognitive impairment compared to those who are regularly active.

Repositioning of Anti-Diabetic Drugs against Dementia: Insight from Molecular Perspectives to Clinical Trials.

Insulin resistance as a hallmark of type 2 DM (T2DM) plays a role in dementia by promoting pathological lesions or enhancing the vulnerability of the brain. Numerous studies related to insulin/insulin-like growth factor 1 (IGF-1) signaling are linked with various types of dementia. Brain insulin resistance in dementia is linked to disturbances in Aß production and clearance, Tau hyperphosphorylation, microglial activation causing increased neuroinflammation, and the breakdown of tight junctions in the blood-brain barrier (BBB). These mechanisms have been studied primarily in Alzheimer's disease (AD), but research on other forms of dementia like vascular dementia (VaD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) has also explored overlapping mechanisms. Researchers are currently trying to repurpose anti-diabetic drugs to treat dementia, which are dominated by insulin sensitizers and insulin substrates. Although it seems promising and feasible, none of the trials have succeeded in ameliorating cognitive decline in late-onset dementia. We highlight the possibility of repositioning anti-diabetic drugs as a strategy for dementia therapy by reflecting on current and previous clinical trials. We also describe the molecular perspectives of various types of dementia through the insulin/IGF-1 signaling pathway.

Melatonin and Exercise Counteract Sarcopenic Obesity through Preservation of Satellite Cell Function.

Sarcopenic obesity (SO) is characterized by atrophic skeletal muscle impairment (sarcopenia) and obesity, which is associated with adverse outcomes of morbidity and mortality in elderly people. We investigated the effects of melatonin and exercise training on SO in 32-week-old senescence-accelerated mouse-prone-8 (SAMP8) mice fed a normal diet or a high-fat diet for 16 weeks. Melatonin, exercise, or melatonin and exercise for 8 weeks displayed reductions in the SO-induced impairment of skeletal muscle function and atrophy. Specifically, a decrease in mitochondrial calcium retention capacity in skeletal muscles observed in the HFD-con group was attenuated in melatonin and/or exercise intervention groups. More importantly, HFD-con mice displayed a lower number of Pax7+ satellite cells (SCs) and higher expression of p16ink than P8ND mice, which were attenuated by melatonin and/or exercise interventions. The cellular senescence in SC-derived primary myoblasts from HFD-con mice was significantly attenuated in myoblasts from the melatonin and/or exercise groups, which was reproduced in a senescence model of H2O2-treated C2C12 myoblasts. Our results suggest that melatonin and exercise training attenuate SO-induced skeletal muscle dysfunction, at least in part, through preserving the SC pool by inhibiting cellular senescence and attenuating mitochondrial dysfunction.

Contribution of High-Intensity Interval Exercise in the Fasted State to Fat Browning: Potential Roles of Lactate and ß-Hydroxybutyrate.

PURPOSE: Fat browning contributes to energy consumption and may have metabolic benefits against obesity; however, the potential roles of lactate and ß-hydroxybutyrate (ß-HB) in fat browning remain unclear. We investigated the roles of a single bout of aerobic exercise that increases lactate and ß-HB levels in the fasted state on the regulation of fat browning in rats and humans. METHODS: Male Sprague-Dawley rats were exposed to 24-h fasting and/or a single bout moderate-intensity aerobic exercise (40 min): sedentary (CON), exercise (ND-EX), fasting (FAST), and exercise + fasting (F-EX). Adult men ( n = 13) were randomly assigned into control with food intake (CON), exercise with intensity at onset of blood lactate accumulation in the fasted state (F-OBLA), and high-intensity interval exercise in the fasted state (F-HIIE) until each participant expended 350 kcal of energy. For evaluating the effects of exercise intensity in rats, we conducted another set of animal experiment, including groups of sedentary fed control, fasting control, and exercise with moderate-intensity or HIIE for 40 min after a 24-h fasting. RESULTS: Regardless of fasting, single bout of exercise increases the concentration of lactate and ß-HB in rats, but the exercise in the fasted state increases the ß-HB level more significantly in rats and humans. F-EX-activated fat browning (AMPK-SirT1-PGC1α pathway and PRDM16) and thermogenic factor (UCP1) in white fat of rats. In rats and humans, exercise in the fasted state increased the blood levels of fat browning-related adipomyokines. In particular, compared with F-OBLA, F-HIIE more efficiently increases free fatty acid as well as blood levels of fat browning adipomyokines in humans, which was correlated with blood levels of lactate and ß-HB. In rats that performed exercise with different intensity, the higher plasma lactate and ß-HB levels, and higher expression of p-AMPK, UCP1, and PRDM16 in white adipose tissue of HIIE group than those of moderate-intensity group, were observed. CONCLUSIONS: A single bout of aerobic exercise in the fasted state significantly induced fat browning-related pathways, free fatty acid, and adipomyokines, particularly F-HIIE in human. Although further evidence for supporting our results is required in humans, aerobic exercise in the fasted state with high intensity that increase lactate and ß-HB may be a modality of fat browning.

Protective effect of TPP-Niacin on microgravity-induced oxidative stress and mitochondrial dysfunction of retinal epithelial cells.

Adverse effects of spaceflight on the human body are attritubuted to microgravity and space radiation. One of the most sensitive organs affected by them is the eye, particularly the retina. The conditions that astronauts suffer, such as visual acuity, is collectively called a spaceflight-associated neuro-ocular syndrome (SANS); however, the underlying molecular mechanism of the microgravity-induced ocular pathogenesis is not clearly understood. The current study explored how microgravity affects the retina function in ARPE19 cells in vitro under time-averaged simulated microgravity (µG) generated by clinostat. We found multicellular spheroid (MCS) formation and a significantly decreased cell migration potency under µG conditions compared to 1G in ARPE19 cells. We also observed that µG increases intracellular reactive oxygen species (ROS) and causes mitochondrial dysfunction in ARPE19 cells. Subsequently, we showed that µG activates autophagic pathways and ciliogenesis. Furthermore, we demonstrated that mitophagy activation is triggered via the mTOR-ULK1-BNIP3 signaling axis. Finally, we validated the effectiveness of TPP-Niacin in mitigating µG-induced oxidative stress and mitochondrial dysfunction in vitro, which provides the first experimental evidence for TPP-Niacin as a potential therapeutic agent to ameliorate the cellular phenotypes caused by µG in ARPE19 cells. Further investigations are, however, required to determine its physiological functions and biological efficacies in primary human retinal cells, in vivo models, and target identification.

Circulating micro-RNAs Differentially Expressed in Korean Alzheimer's Patients With Brain Aß Accumulation Activate Amyloidogenesis.

BACKGROUND: Roles for extracellular vesicles (EVs) enriched with micro-RNAs (miRNAs) have been proposed in Alzheimer's disease (AD) pathogenesis, leading to the discovery of blood miRNAs as AD biomarkers. However, the diagnostic utility of specific miRNAs is not consistent. This study aimed to discover blood miRNAs that are differentially expressed in Korean AD patients, evaluate their clinical performance, and investigate their role in amyloidogenesis. METHODS: We discovered miRNAs differentially expressed in AD (N = 8) from cognitively normal participants (CN, N = 7) or Parkinson's disease (PD) patients (N = 8). We evaluated the clinical performance of these miRNAs in plasma of subgroup (N = 99) and in plasma EVs isolated from the total cohort (N = 251). The effects of miRNAs on amyloidogenesis and on the regulation of their target genes were investigated in vitro. RESULTS: Among 17 upregulated and one downregulated miRNAs in AD (>twofold), miR-122-5p, miR-210-3p, and miR-590-5p were differentially expressed compared with CN or PD. However, the diagnostic performance of the selected plasma or EV miRNAs in total participants were limited (area under the curve < 0.8). Nevertheless, levels of 3 miRNAs in plasma or plasma EVs of participants who were amyloid positron emission tomography (Aß-PET) positive were significantly higher than those from the Aß-PET negative participants (p < .05). The selected miRNAs induced Aß production (p < .05) through activation of ß-cleavage of amyloid precursor protein (CTF-ß; p < .01), and downregulated their target genes (ADAM metallopeptidase domain 10, Brain-derived neurotrophic factor, and Jagged canonical notch ligand 1; p < .05), which was further supported by pathway enrichment analysis of target genes of the miRNAs. CONCLUSION: In conclusion, despite of the limited diagnostic utility of selected miRNAs as plasma or plasma EV biomarkers, the discovered miRNAs may play a role in amyloidogenesis during AD onset and progression.

Dynapenic-abdominal obesity as an independent risk factor for chronic kidney disease in postmenopausal women: a population-based cohort study.

OBJECTIVE: Low muscle strength and obesity lead to a higher risk of chronic kidney disease (CKD). Perimenopause is associated with a natural decline in muscle strength and an increase in visceral adiposity. Dynapenic obesity, which is the coexistence of low muscle strength and obesity, is expected to synergistically increase the prevalence of CKD in postmenopausal women. The aim of this study was to determine combined associations of dynapenia and obesity with CKD in postmenopausal women. METHODS: This study used data from the Korean National Health and Nutrition Examination Survey, 2016 to 2019. The study included 4,525 postmenopausal women aged 42 to 80 years that were classified into four groups based on waist circumference (≥85 cm) and hand grip strength (<18 kg): normal, dynapenic, obese, or dynapenic-obese. According to the Kidney Disease: Improving Global Outcomes, we defined CKD as an estimated glomerular filtration rate <60 mL/min per 1.73 m2. Complex sample logistic regression models were conducted to determine the relationships among coexistence of dynapenia, abdominal obesity, and the risk of CKD. RESULTS: Dynapenic-abdominal obese group displayed lower estimated glomerular filtration rate levels than other groups (P < 0.05 for all data). The prevalence rates of CKD were 15.5%, 7.8%, 6.2%, and 2.4% in the dynapenic-abdominal obese, dynapenic, abdominal obese, and normal groups, respectively (P < 0.001). Complex sample logistic regression analyses, after adjusting for age, height, health behaviors, and comorbidities, showed that the odds ratio for CKD with respect to dynapenic-abdominal obesity was 1.82 (95% confidence interval, 1.19-2.79) and to abdominal obesity was 1.54 (95% confidence interval, 1.07-2.22) than in the normal group. CONCLUSIONS: This study demonstrated that dynapenic-abdominal obesity, as determined by low handgrip strength and high waist circumference values, was associated with increased risk of CKD in postmenopausal women.

Development of Alzheimer's Disease Biomarkers: From CSF- to Blood-Based Biomarkers.

In the 115 years since the discovery of Alzheimer's disease (AD), our knowledge, diagnosis, and therapeutics have significantly improved. Biomarkers are the primary tools for clinical research, diagnostics, and therapeutic monitoring in clinical trials. They provide much insightful information, and while they are not clinically used routinely, they help us to understand the mechanisms of this disease. This review charts the journey of AD biomarker discovery and development from cerebrospinal fluid (CSF) amyloid-beta 1-42 (Aß42), total tau (T-tau), and phosphorylated tau (p-tau) biomarkers and imaging technologies to the next generation of biomarkers. We also discuss advanced high-sensitivity assay platforms for CSF Aß42, T-tau, p-tau, and blood analysis. The recently proposed Aß deposition/tau biomarker/neurodegeneration or neuronal injury (ATN) scheme might facilitate the definition of the biological status underpinning AD and offer a common language among researchers across biochemical biomarkers and imaging. Moreover, we highlight blood-based biomarkers for AD that offer a scalable alternative to CSF biomarkers through cost-saving and reduced invasiveness, and may provide an understanding of disease initiation and development. We discuss different groups of blood-based biomarker candidates, their advantages and limitations, and paths forward, from identification and analysis to clinical validation. The development of valid blood-based biomarkers may facilitate the implementation of future AD therapeutics and diagnostics.

Role of exercise in estrogen deficiency-induced sarcopenia.

A decline in estrogen levels during menopause is associated with the loss of muscle mass and function, and it can accelerate sarcopenia. However, with the growing number of postmenopausal women due to the increase in life expectancy, the effects of estrogen on skeletal muscle are not completely understood. This article reviews the relationship between estrogen deficiency and skeletal muscle, its potential mechanisms, including those involving mitochondria, and the effects of exercise on estrogen deficiency-induced skeletal muscle impairment. In particular, mitochondrial dysfunction induced by estrogen deficiency accelerates sarcopenia via mitochondrial dynamics, mitophagy, and mitochondrial-mediated apoptosis. It is well known that exercise training is essential for health, including for the improvement of sarcopenia. This review highlights the importance of exercise training (aerobic and resistance exercise) as a therapeutic intervention against estrogen deficiency-induced sarcopenia.

Effects of nocturnal light exposure on circadian rhythm and energy metabolism in healthy adults: A randomized crossover trial.

Exposure to continuous light at night, including night-shift work or a nocturnal lifestyle, is emerging as a novel deleterious factor for weight gain and obesity. Here, we examined whether a single bout of bright light (BL) exposure at night affects energy metabolism via changes in circadian rhythm and nocturnal melatonin production. Ten healthy young men were randomized to a two-way crossover experimental design protocol: control (< 50 lux) and BL (approximately 10000 lux) conditions, with at least seven days of interval. The participants were exposed to each condition for 3 h (21:00-24:00) before sleep (0 lux, 00:00-07:00) in a room-type metabolic chamber. On each experimental night (21:00-07:00), energy expenditure, respiratory quotient (RQ), and substrate oxidation were measured to determine the energy metabolism. BL exposure prior to bedtime altered biological rhythms, disrupted the nocturnal decline in body temperature, and suppressed the melatonin level before sleeping, resulting in an increase in sleep latency. Indirect calorimetry data revealed that BL exposure significantly decreased the fat oxidation and increased the RQ, an indicator of the carbohydrate-to-fat oxidation ratio, throughout the whole period (light exposure and sleep). We revealed that acute BL exposure prior to bedtime exacerbated circadian rhythms and substrate oxidations, suggesting that chronic BL exposure at night may lead to obesity risk due to disturbances in circadian rhythms and macronutrient metabolism.

Exercise Training Attenuates Ovariectomy-Induced Alterations in Skeletal Muscle Remodeling, Apoptotic Signaling, and Atrophy Signaling in Rat Skeletal Muscle.

PURPOSE: The effects of aerobic exercise training on soleus muscle morphology, mitochondria-mediated apoptotic signaling, and atrophy/hypertrophy signaling in ovariectomized rat skeletal muscle were investigated. METHODS: Female Sprague-Dawley rats were divided into control (CON), ovariectomy (OVX), and ovariectomy plus exercise (OVX+EX) groups. After ovarian excision, exercise training was performed using a rat treadmill at 20 m/min, 50 min/day, 5 days/week for 12 weeks. Protein levels of mitochondria-mediated apoptotic signaling and atrophy/hypertrophy signaling in the skeletal muscle (soleus) were examined through western immunoblot analysis. RESULTS: The number of myocytes and myocyte cross-sectional area (CSA) were increased and the extramyocyte space was decreased in the OVX group compared to those in the CON group. However, aerobic exercise training significantly increased myocyte CSA and decreased extramyocyte space in the OVX+EX group compared to those in the OVX group. The protein levels of proapoptotic signaling and muscle atrophy signaling were significantly increased, whereas the protein levels of muscle hypertrophy signaling were significantly decreased in the OVX group compared to that in the CON group. Aerobic exercise training significantly decreased the protein levels of proapoptotic signaling and increased the protein level of antiapoptotic protein in the OVX+EX group compared to that in the OVX group. Aerobic exercise training significantly increased the protein levels of hypertrophy signaling and decreased protein levels of atrophy signaling in the OVX+EX group compared to those in the OVX group. CONCLUSION: Treadmill exercise improved estrogen deficiency-induced impairment in skeletal muscle remodeling, mitochondria-mediated apoptotic signaling, and atrophy/hypertrophy signaling in 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.

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].

Relationships between Socioeconomic Status, Handgrip Strength, and Non-Alcoholic Fatty Liver Disease in Middle-Aged Adults.

Although low socioeconomic status (SES) and decreased muscle strength have been found to be associated with the risk factors of non-alcoholic fatty liver disease (NAFLD), including insulin resistance, obesity, and metabolic syndrome, the associations among SES, muscle strength, and NAFLD are still unclear. We aimed to investigate the combined effect of SES and relative handgrip strength (HGS) on the risk of NAFLD in middle-aged adults. Data from 5272 middle-aged adults who participated in the Korea National Health and Nutrition Examination Surveys (KNHANES) from 2014-2018 were analyzed. NAFLD was defined using the hepatic steatosis index (HSI) > 36 and the comprehensive NAFLD score (CNS) ≥ 40 in the absence of other causes of liver disease. SES was based on a self-reported questionnaire. Overall, individuals with low SES (odds ratio (OR) = 1.703, 95% confidence interval (CI): 1.424-2.037, p < 0.001) or low HGS (OR = 12.161, 95% CI: 9.548-15.488, p < 0.001) had a significantly higher risk of NAFLD. The joint association analysis showed that a low SES combined with a low HGS (OR = 2.479, 95% CI: 1.351-4.549, p = 0.003) further significantly increased the risk of NAFLD when adjusted for all the covariates, compared with individuals with a high SES and a high HGS (OR = 1). The current findings suggest that both low SES and low HGS were independently and synergistically associated with an increased risk of NAFLD in middle-aged Korean adults.

Personalized Healthcare for Dementia.

Dementia is one of the most common health problems affecting older adults, and the population with dementia is growing. Dementia refers to a comprehensive syndrome rather than a specific disease and is characterized by the loss of cognitive abilities. Many factors are related to dementia, such as aging, genetic profile, systemic vascular disease, unhealthy diet, and physical inactivity. As the causes and types of dementia are diverse, personalized healthcare is required. In this review, we first summarize various diagnostic approaches associated with dementia. Particularly, clinical diagnosis methods, biomarkers, neuroimaging, and digital biomarkers based on advances in data science and wearable devices are comprehensively reviewed. We then discuss three effective approaches to treating dementia, including engineering design, exercise, and diet. In the engineering design section, recent advances in monitoring and drug delivery systems for dementia are introduced. Additionally, we describe the effects of exercise on the treatment of dementia, especially focusing on the effects of aerobic and resistance training on cognitive function, and the effects of diets such as the Mediterranean diet and ketogenic diet on dementia.