Methylene Blue Pretreatment Protects Against Repeated Neonatal Isoflurane Exposure-Induced Brain Injury and Memory Loss.

Perioperative neurocognitive impairment (PND) is a common medical complication in the postoperative period. General anesthesia through volatile anesthetics poses a high risk of POCD. Moreover, the developing brain is especially vulnerable to anesthesia-induced neurotoxicity. Therefore, finding a practical approach to prevent or alleviate neonatal isoflurane (ISO) exposure-induced brain injury and cognitive decline is essential for reducing medical complications following major surgery during the early postnatal period. Using a repeated neonatal ISO exposure-induced PND rat model, we investigated the effects of methylene blue (MB) pretreatment on repeated neonatal isoflurane exposure-induced brain injury and memory loss. Intraperitoneal injection of low-dose MB (1 mg/kg) was conducted three times 24 h before each ISO exposure. The Barnes maze and novel objection test were conducted to assess learning and memory. Immunofluorescence staining, F-Jade C staining, TUNEL staining, and Western blot analysis were performed to determine mitochondrial fragmentation, neuronal injury, degeneration, and apoptosis. Evans blue extravasation assay, total antioxidant capacity assay, MDA assay kit, and related inflammatory assay kits were used to test blood-brain barrier (BBB) disruption, antioxidant capacity, and neuroinflammation. Behavioral tests revealed that MB pretreatment significantly ameliorated ISO exposure-induced cognitive deficits. In addition, MB pretreatment alleviates neuronal injury, apoptosis, and degeneration. Furthermore, the BBB integrity was preserved by MB pretreatment. Additional studies revealed that ISO-induced excessive mitochondrial fragmentation, oxidative stress, and neuroinflammation were significantly attenuated by MB pretreatment in the PND rat model. Our findings suggest that MB pretreatment alleviates ISO exposure-induced brain injury and memory loss for the first time, supporting MB pretreatment as a promising approach to protect the brain against neonatal ISO exposure-induced postoperative cognitive dysfunction.

Photobiomodulation therapy alleviates repeated closed head injury-induced anxiety-like behaviors.

Repeated closed head injury (rCHI) is one of the most common brain injuries. Although extensive studies have focused on how to treat rCHI-induced brain injury and reduce the possibility of developing memory deficits, the prevention of rCHI-induced anxiety has received little research attention. The current study was designed to assess the effects of photobiomodulation (PBM) therapy in preventing anxiety following rCHI. The rCHI disease model was constructed by administering three repeated closed-head injuries within an interval 5 days. 2-min daily PBM therapy using an 808 nm continuous wave laser at 350 mW/cm2 on the scalp was implemented for 20 days. We found that PBM significantly ameliorated rCHII-induced anxiety-like behaviors, neuronal apoptosis, neuronal injury, promotes astrocyte/microglial polarization to anti-inflammatory phenotype, preserves mitochondrial fusion-related protein MFN2, attenuates the elevated mitochondrial fission-related protein DRP1, and mitigates neuronal senescence. We concluded that PBM therapy possesses great potential in preventing anxiety following rCHI.

Mechanism of action of photobiomodulation with light-emitting diode on the glutamine-dependent CT26 cell.

We investigated the mechanism of action of photobiomodulation (PBM) with light-emitting diode (led) 640 nm of glutamine-dependent CT26 cells. Cells were exposed to 0.147-10.979 mW/cm2 of 640 ± 15 nm laser light for 15 min/day for 10 days. Cell proliferation and apoptosis were detected by MTT (3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide) and annexin V-FITC assays. mRNA and protein levels of cell proliferation-related genes were measured by RT-PCR and western blotting, respectively. With Gln 7.94 mM, on Day 8 and 10, genes GLUT1, MEK1, ERK2, BCL2, E2F1, HO-1, Ctnnb1, and Per2 was significantly upregulated (p < 0.01) of glutamine addiction. In PBM therapy, compared with the non-illuminated group, 2.17 mW/cm2 can significantly reduce cell apoptosis, the mRNA level of gene mTOR1 was significantly upregulated, and the protein level of raptor of GLUT1 and mTOR1, MEK1/2, and ERK1/2 were upregulated. LED 640 nm inhibits cell apoptosis without increasing cell proliferation by regulating GLUT1, MEK/ERK, and PI3K/AKT/mTOR signals.

Oligodendrocyte progenitor cells in Alzheimer's disease: from physiology to pathology.

Oligodendrocyte progenitor cells (OPCs) play pivotal roles in myelin formation and phagocytosis, communicating with neighboring cells and contributing to the integrity of the blood-brain barrier (BBB). However, under the pathological circumstances of Alzheimer's disease (AD), the brain's microenvironment undergoes detrimental changes that significantly impact OPCs and their functions. Starting with OPC functions, we delve into the transformation of OPCs to myelin-producing oligodendrocytes, the intricate signaling interactions with other cells in the central nervous system (CNS), and the fascinating process of phagocytosis, which influences the function of OPCs and affects CNS homeostasis. Moreover, we discuss the essential role of OPCs in BBB formation and highlight the critical contribution of OPCs in forming CNS-protective barriers. In the context of AD, the deterioration of the local microenvironment in the brain is discussed, mainly focusing on neuroinflammation, oxidative stress, and the accumulation of toxic proteins. The detrimental changes disturb the delicate balance in the brain, impacting the regenerative capacity of OPCs and compromising myelin integrity. Under pathological conditions, OPCs experience significant alterations in migration and proliferation, leading to impaired differentiation and a reduced ability to produce mature oligodendrocytes. Moreover, myelin degeneration and formation become increasingly active in AD, contributing to progressive neurodegeneration. Finally, we summarize the current therapeutic approaches targeting OPCs in AD. Strategies to revitalize OPC senescence, modulate signaling pathways to enhance OPC differentiation, and explore other potential therapeutic avenues are promising in alleviating the impact of AD on OPCs and CNS function. In conclusion, this review highlights the indispensable role of OPCs in CNS function and their involvement in the pathogenesis of AD. The intricate interplay between OPCs and the AD brain microenvironment underscores the complexity of neurodegenerative diseases. Insights from studying OPCs under pathological conditions provide a foundation for innovative therapeutic strategies targeting OPCs and fostering neurodegeneration. Future research will advance our understanding and management of neurodegenerative diseases, ultimately offering hope for effective treatments and improved quality of life for those affected by AD and related disorders.

Evaluating the Effect of Artificial Liver Support on Acute-on-Chronic Liver Failure Using the Quantitative Difference Algorithm: Retrospective Study.

BACKGROUND: Liver failure, including acute-on-chronic liver failure (ACLF), occurs mainly in young adults and is associated with high mortality and resource costs. The prognosis evaluation is a crucial part of the ACLF treatment process and should run through the entire diagnosis process. As a recently proposed novel algorithm, the quantitative difference (QD) algorithm holds promise for enhancing the prognosis evaluation of ACLF. OBJECTIVE: This study aims to examine whether the QD algorithm exhibits comparable or superior performance compared to the Model for End-Stage Liver Disease (MELD) in the context of prognosis evaluation. METHODS: A total of 27 patients with ACLF were categorized into 2 groups based on their treatment preferences: the conventional treatment (n=12) and the double plasma molecular absorption system (DPMAS) with conventional treatment (n=15) groups. The prognosis evaluation was performed by the MELD and QD scoring systems. RESULTS: A significant reduction was observed in alanine aminotransferase (P=.02), aspartate aminotransferase (P<.001), and conjugated bilirubin (P=.002), both in P values and QD value (Lτ>1.69). A significant decrease in hemoglobin (P=.01), red blood cell count (P=.01), and total bilirubin (P=.02) was observed in the DPMAS group, but this decrease was not observed in QD (Lτ≤1.69). Furthermore, there was a significant association between MELD and QD values (P<.001). Significant differences were observed between groups based on patients' treatment outcomes. Additionally, the QD algorithm can also demonstrate improvements in patient fatigue. DPMAS can reduce alanine aminotransferase, aspartate aminotransferase, and unconjugated bilirubin. CONCLUSIONS: As a dynamic algorithm, the QD scoring system can evaluate the therapeutic effects in patients with ACLF, similar to MELD. Nevertheless, the QD scoring system surpasses the MELD by incorporating a broader range of indicators and considering patient variability.

Microglia and Astrocytes in Alzheimer's Disease: Significance and Summary of Recent Advances.

Alzheimer's disease, one of the most common forms of dementia, is characterized by a slow progression of cognitive impairment and neuronal loss. Currently, approved treatments for AD are hindered by various side effects and limited efficacy. Despite considerable research, practical treatments for AD have not been developed. Increasing evidence shows that glial cells, especially microglia and astrocytes, are essential in the initiation and progression of AD. During AD progression, activated resident microglia increases the ability of resting astrocytes to transform into reactive astrocytes, promoting neurodegeneration. Extensive clinical and molecular studies show the involvement of microglia and astrocyte-mediated neuroinflammation in AD pathology, indicating that microglia and astrocytes may be potential therapeutic targets for AD. This review will summarize the significant and recent advances of microglia and astrocytes in the pathogenesis of AD in three parts. First, we will review the typical pathological changes of AD and discuss microglia and astrocytes in terms of function and phenotypic changes. Second, we will describe microglia and astrocytes' physiological and pathological role in AD. These roles include the inflammatory response, "eat me" and "don't eat me" signals, Aß seeding, propagation, clearance, synapse loss, synaptic pruning, remyelination, and demyelination. Last, we will review the pharmacological and non-pharmacological therapies targeting microglia and astrocytes in AD. We conclude that microglia and astrocytes are essential in the initiation and development of AD. Therefore, understanding the new role of microglia and astrocytes in AD progression is critical for future AD studies and clinical trials. Moreover, pharmacological, and non-pharmacological therapies targeting microglia and astrocytes, with specific studies investigating microglia and astrocyte-mediated neuronal damage and repair, may be a promising research direction for future studies regarding AD treatment and prevention.

Exogenous lactate administration: A potential novel therapeutic approach for neonatal hypoxia-ischemia.

Neonatal hypoxic-ischemic encephalopathy (HIE) is the primary reason for neonatal mortality and prolonged disablement. Currently, hypothermia is the only approved clinical treatment available for HIE. However, hypothermia's limited therapeutic efficacy and adverse effects suggest an urgent need to advance our knowledge of its molecular pathogenesis and develop novel therapies. The leading cause of HIE is impaired cerebral blood flow and oxygen deprivation-initiated primary and secondary energy failure. Lactate was traditionally regarded as a marker of energy failure or a waste product of anaerobic glycolysis. Recently, the beneficial aspects of lactate as supplementary energy for neurons have been demonstrated. Under the conditions of HI, lactate supports various functions of neuronal cells, including learning and memory formation, motor coordination, and somatosensory. Furthermore, lactate contributes to the regeneration of blood vessels and has shown its beneficial effects on the immune system. This review first introduces the hypoxic or ischemic events-induced fundamental pathophysiological changes in HIE and then discusses the potential neuroprotective properties of lactate for the treatment and prevention of HIE. Finally, we discuss the possible protective mechanisms of lactate in the context of the pathological features of perinatal HIE. We conclude that exogenous and endogenous lactate exert neuroprotective effects in HIE. Lactate administration may be a potential approach to treating HIE injury.

High-intensity interval training ameliorates Alzheimer's disease-like pathology by regulating astrocyte phenotype-associated AQP4 polarization.

Background: Alzheimer's disease (AD), one of the most common forms of dementia, is a widely studied neurodegenerative disease characterized by Aß accumulation and tau hyperphosphorylation. Currently, there is no effective cure available for AD. The astrocyte AQP4 polarized distribution-mediated glymphatic system is essential for Aß and abnormal tau clearance and is a potential therapeutic target for AD. However, the role of exercise on the AQP4 polarized distribution and the association between the AQP4 polarized distribution and astrocyte phenotype polarization are poorly understood. Methods: Using a streptozotocin (STZ)-induced sporadic AD rat model, we investigated the effects of high-intensity interval training on AD pathologies. The Branes maze task was conducted to measure spatial learning and memory. Immunofluorescence staining of NeuN with TUNEL, Fluoro-Jade C, and relative neuronal damage markers was applied to measure neuronal apoptosis, neurodegeneration, and damage. Sholl analysis was carried out to analyze the morphology of microglia. Line-scan analysis, 3D rendering, and the orthogonal view were applied to analyze the colocalization. Western blot analysis and enzyme-linked immunosorbent assay (ELISA) analysis were conducted to examine AQP4 and Aß, respectively. An APP/PS1 transgenic AD mice model was used to confirm the key findings. Results: High-intensity interval training (HIIT) alleviates cognitive dysfunction in STZ-induced AD-like rat models and provides neuroprotection against neurodegeneration, neuronal damage, and neuronal loss. Additionally, HIIT improved the drainage of abnormal tau and Aß from the cortex and hippocampus via the glymphatic system to the kidney. Further mechanistic studies support that the beneficial effects of HIIT on AD might be due, in part, to the polarization of glial cells from a neurotoxic phenotype towards a neuroprotective phenotype. Furthermore, an intriguing finding of our study is that the polarized distribution of AQP4 was strongly correlated with astrocyte phenotype. We found A2 phenotype exhibited more evident AQP4 polarization than the A1 phenotype. Conclusion: Our findings indicate that HIIT ameliorates Alzheimer's disease-like pathology by regulating astrocyte phenotype and astrocyte phenotype-associated AQP4 polarization. These changes promote Aß and p-tau clearance from the brain tissue through the glymphatic system and the kidney.

Neuroprotective Effect of Sub-lethal Hyperthermia Preconditioning in a Rat Model of Repeated Closed Head Injury.

Repeated mild traumatic brain injury (rTBI), one of the most common forms of traumatic brain injury, is a worldwide severe public health concern. rTBI induces cumulative neuronal injury, neurological dysfunction, and cognitive deficits. Although there are clinical treatment methods, there is still an urgent need to develop preventive approaches for susceptible populations. Using a repeated closed head injury (rCHI) rat model, we interrogate the effect of sub-lethal hyperthermia preconditioning (SHP) on rCHI-induced neuronal injury and behavioral changes. Our study applied the repeated weight-drop model to induce the rCHI. According to the changes of heat shock protein 70 (HSP 70) in the cortex and hippocampus following a single SHP treatment in normal rats, the SHP was delivered to the rats 18 h before rCHI. We found that HSP significantly alleviated rCHI-induced anxiety-like behaviors and impairments in motor abilities and spatial memory. SHP exerts significant neuroprotection against rCHI-induced neuronal damage, apoptosis, and neuroinflammation. Our findings support the potential use of SHP as a preventative approach for alleviating rCHI-induced brain damage.

Rapid quantification of goat milk adulteration with cow milk using Raman spectroscopy and chemometrics.

As goat milk has a higher economic value compared to cow milk, the phenomenon of adulterating goat milk with cow milk appears in the market. In this study, the potential of Raman spectroscopy along with chemometrics was investigated for the authentication and quantitation of liquid goat milk adulterated with cow milk. First, the results of principal component analysis (PCA) showed that there were differences between the Raman spectra of cow and goat milk, which made quantitative experiments possible. For quantification, three different brands of cow milk and goat milk were selected randomly and adulterated goat milk with cow milk at the proportion of 5-95%. 342 samples were used for the construction of the partial least squares regression (PLSR) model with 80% for the calibration set and 20% for the prediction set. The PLSR model showed excellent performance in quantifying the level of adulteration, for the prediction set, with a coefficient of determination (R2) of 0.9781, root mean square error (RMSE) of 3.82%, and a ratio of prediction to deviation (RPD) of 6.8. The results demonstrated the potential of Raman spectroscopy as a rapid, low cost and non-destructive analytical tool for detecting adulteration in goat milk.

Molecular Hydrogen: an Emerging Therapeutic Medical Gas for Brain Disorders.

Oxidative stress and neuroinflammation are the main physiopathological changes involved in the initiation and progression of various neurodegenerative disorders or brain injuries. Since the landmark finding reported in 2007 found that hydrogen reduced the levels of peroxynitrite anions and hydroxyl free radicals in ischemic stroke, molecular hydrogen's antioxidative and anti-inflammatory effects have aroused widespread interest. Due to its excellent antioxidant and anti-inflammatory properties, hydrogen therapy via different routes of administration exhibits great therapeutic potential for a wide range of brain disorders, including Alzheimer's disease, neonatal hypoxic-ischemic encephalopathy, depression, anxiety, traumatic brain injury, ischemic stroke, Parkinson's disease, and multiple sclerosis. This paper reviews the routes for hydrogen administration, the effects of hydrogen on the previously mentioned brain disorders, and the primary mechanism underlying hydrogen's neuroprotection. Finally, we discuss hydrogen therapy's remaining issues and challenges in brain disorders. We conclude that understanding the exact molecular target, finding novel routes, and determining the optimal dosage for hydrogen administration is critical for future studies and applications.

Therapeutic non-invasive brain treatments in Alzheimer's disease: recent advances and challenges.

Alzheimer's disease (AD) is one of the major neurodegenerative diseases and the most common form of dementia. Characterized by the loss of learning, memory, problem-solving, language, and other thinking abilities, AD exerts a detrimental effect on both patients' and families' quality of life. Although there have been significant advances in understanding the mechanism underlying the pathogenesis and progression of AD, there is no cure for AD. The failure of numerous molecular targeted pharmacologic clinical trials leads to an emerging research shift toward non-invasive therapies, especially multiple targeted non-invasive treatments. In this paper, we reviewed the advances of the most widely studied non-invasive therapies, including photobiomodulation (PBM), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and exercise therapy. Firstly, we reviewed the pathological changes of AD and the challenges for AD studies. We then introduced these non-invasive therapies and discussed the factors that may affect the effects of these therapies. Additionally, we review the effects of these therapies and the possible mechanisms underlying these effects. Finally, we summarized the challenges of the non-invasive treatments in future AD studies and clinical applications. We concluded that it would be critical to understand the exact underlying mechanisms and find the optimal treatment parameters to improve the translational value of these non-invasive therapies. Moreover, the combined use of non-invasive treatments is also a promising research direction for future studies and sheds light on the future treatment or prevention of AD.

On the Biomarkers of Alzheimer's Disease.

Nakamura et al. examined the evidence, using a discovery and a validation database, that amyloid-ß precursor protein (APP)669-711/amyloid-ß (Aß)1-42 and Aß1-40/Aß1-42 ratios, and composites based on traditional statistics; they concluded that these may be useful as biomarkers of Alzheimer's Disease (AD). We reexamined the same datasets, each of which included cognitively normal individuals (CN), individuals with mild cognitive impairment (MCI) and individuals with AD. We used fractal self-similar analyses and reexamined their data from (1) the Japanese National Center for Geriatrics and Gerontology (NCGG) (discovery database) and (2) the Australian Imaging, Biomarker and Lifestyle Study of Ageing (AIBL) cohort (validation database). Results: Using our methods, the three groups of individuals were found to be self-similar, i.e., they could not be differentiated quantitatively, in contrast to the findings of Nakamura et al. Conclusion: Appropriate biomarkers need further study. Our results suggest that APP669-711/Aß1-42 and Aß1-40/Aß1-42 ratios and their composites may not be valid biomarkers of AD, when reexamined using fractal methods for comparing biomarkers across populations.

MiR-214 Attenuates the Osteogenic Effects of Mechanical Loading on Osteoblasts.

Exercise is an effective way to prevent osteoporosis, but its mechanism remains unclear. MicroRNAs (miRNAs) play an essential role in bone metabolism. Recently, mechanical loading was reported to induce changes in miRNA expression in osteoblasts. However, the role of miRNAs in bone under exercise and its underlining mechanisms of action still remain unknown. MiR-214 was reported to regulate the process of osteogenesis and is considered a biomarker of osteoporosis. In this study, we aimed to investigate whether exercise could induce changes in miRNA expression in bone and to study the effects of miR-214 on mechanical loading-induced osteogenesis in osteoblasts. The results showed that miR-214 was down-regulated in both tibia from C57BL/6 mice after exercise in vivo and in osteoblasts after mechanical strain in vitro. Mechanical strain could enhance the ALP activity, promote matrix mineralization, up-regulate the expression of osteogenic factors such as ATF4, Osterix, ALP and ß-catenin, and down-regulate RANKL and RANK expression. Over-expression of miR-214 not only inhibited the expression of these osteogenic factors but also attenuated mechanical strain-enhanced osteogenesis in osteoblasts. Collectively, our results indicated that miR-214 could attenuate the osteogenic effects of mechanical loading on osteoblasts, suggesting that inhibition of miR-214 may be one of the ways in which exercise prevents osteoporosis.

Rapid Detection of Adulterants in Whey Protein Supplement by Raman Spectroscopy Combined with Multivariate Analysis.

The growing demand for whey protein supplements has made them the target of adulteration with cheap substances. Therefore, Raman spectroscopy in tandem with chemometrics was proposed to simultaneously detect and quantify three common adulterants (creatine, l-glutamine and taurine) in whey protein concentrate (WPC) powder. Soft independent modeling class analogy (SIMCA) and partial least squares discriminant analysis (PLS-DA) models were built based on two spectral regions (400-1800 cm-1 and 500-1100 cm-1) to classify different types of adulterated samples. The most effective was the SIMCA model in 500-1100 cm-1 with an accuracy of 96.9% and an error rate of 5%. Partial least squares regression (PLSR) models for each adulterant were developed using two different Raman spectral ranges (400-1800 cm-1 and selected specific region) and data pretreatment methods. The determination coefficients (R2) of all models were higher than 0.96. PLSR models based on typical Raman regions (500-1100 cm-1 for creatine and taurine, the combination of range 800-1000 cm-1 and 1300-1500 cm-1 for glutamine) were superior to models in the full spectrum. The lowest root mean squared error of prediction (RMSEP) was 0.21%, 0.33%, 0.42% for creatine, taurine and glutamine, and the corresponding limit of detection (LOD) values for them were 0.53%, 0.71% and 1.13%, respectively. This proves that Raman spectroscopy with the help of multivariate approaches is a powerful method to detect adulterants in WPC.

A Noninvasive Accurate Measurement of Blood Glucose Levels with Raman Spectroscopy of Blood in Microvessels.

Raman spectra of human skin obtained by laser excitation have been used to non-invasively detect blood glucose. In previous reports, however, Raman spectra thus obtained were mainly derived from the epidermis and interstitial fluid as a result of the shallow penetration depth of lasers in skin. The physiological process by which glucose in microvessels penetrates into the interstitial fluid introduces a time delay, which inevitably introduces errors in transcutaneous measurements of blood glucose. We focused the laser directly on the microvessels in the superficial layer of the human nailfold, and acquired Raman spectra with multiple characteristic peaks of blood, which indicated that the spectra obtained predominantly originated from blood. Incorporating a multivariate approach combining principal component analysis (PCA) and back propagation artificial neural network (BP-ANN), we performed noninvasive blood glucose measurements on 12 randomly selected volunteers, respectively. The mean prediction performance of the 12 volunteers was obtained as an RMSEP of 0.45 mmol/L and R2 of 0.95. It was no time lag between the predicted blood glucose and the actual blood glucose in the oral glucose tolerance test (OGTT). We also applied the procedure to data from all 12 volunteers regarded as one set, and the total predicted performance was obtained with an RMSEP of 0.27 mmol/L and an R2 of 0.98, which is better than that of the individual model for each volunteer. This suggested that anatomical differences between volunteer fingernails do not reduce the prediction accuracy and 100% of the predicted glucose concentrations fall within Region A and B of the Clarke error grid, allowing acceptable predictions in a clinically relevant range. The Raman spectroscopy detection of blood glucose from microvessels is of great significance of non-invasive blood glucose detection of Raman spectroscopy. This innovative method may also facilitate non-invasive detection of other blood components.

Beneficial alterations in body composition, physical performance, oxidative stress, inflammatory markers, and adipocytokines induced by long-term high-intensity interval training in an aged rat model.

Sarcopenia is associated with loss of muscle mass and function as well as oxidative stress, chronic low-grade inflammatory status, and adipocytokine dysfunction. It has been reported that sarcopenia can be attenuated by exercise training. The purpose of this study was to evaluate whether long-term high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) protocols could differentially modulate changes in body composition, physical performance, inflammatory parameters, and adipocytokines in fat tissues and serum, as well as oxidative parameters and insulin-like growth factor 1 (IGF-1) levels in skeletal muscle tissue of aged rats. Middle-aged (18-month-old) female Sprague Dawley rats (n = 36) were subjected to 8 months of MICT (26-m MICT) or HIIT (26-m HIIT) treadmill training (45 min, 5 times per week), and the results were compared with those of age-matched sedentary controls (26-m SED); 8-month-old (8-m SED) and 18-month-old (18-m SED) rats served as aging sedentary controls. Body composition parameters; physical performance; serum and skeletal muscle oxidative stress parameters; levels of IGF-1, a serum and fat tissue inflammatory marker; adipocytokine (leptin, adiponectin) levels; and plasma glucose and lipid metabolism-related parameters were analyzed among the five groups. The percent fat and body fat to lean mass ratio increased as a main effect with age, whereas 26-m HIIT but not 26-m MICT attenuated these alterations. The 26-m HIIT group showed a larger improvement in grip strength compared to that of 26-m MICT, with a similar increase in inclined plane performance, maximum running speed, and exhaustion over time as compared with the 26-m SED group. Notably, the 26-m HIIT group showed lower high-sensitivity C-reactive protein levels and higher IL-10 in serum compared with those of the 26-m SED and 26-m MICT groups. Both exercise protocols promoted increased skeletal muscle IGF-1 and decreased serum IGF-1 and adiponectin relative to those in the 26-m SED group, whereas only 26-m HIIT dampened the age-related decrease in plasma free fatty acids and increased serum leptin, along with providing lower fat tissue leptin as compared with that in the 26-m SED group. Moreover, the 26-m HIIT group showed lower serum and skeletal muscle malonylaldehyde and skeletal muscle 8-hydroxydeoxyguanosine (8-OHdG) levels than those in the 26-m MICT group, albeit similar decreases in serum and skeletal muscle 4-hydroxynonenal and serum 8-OHdG and increases in skeletal muscle superoxide dismutase 2 activity. In conclusion, HIIT initiated late in life exhibited greater beneficial effects in ameliorating aged-related elevations in oxidative stress and inflammation, as well as dysfunction of circulating adipocytokine levels, than a volume-matched MICT program. HIIT may therefore contribute to improvements in body composition and physical performance changes associated with aging.