The Effects of Photobiomodulation on Knee Function, Pain, and Exercise Tolerance in Older Adults: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To assess whether photobiomodulation therapy (PBMT) enhances the benefits of exercise in older adults. DATA SOURCES: PubMed, Scopus, Medline, and Web of Science, dated to February 2023. STUDY SELECTION: All included studies were randomized controlled trials of PBMT combined with exercise co-intervention in persons 60 years and older. OUTCOME MEASURES: Western Ontario and McMaster University Osteoarthritis Index (WOMAC-total, pain, stiffness and function), perceived pain intensity, timed Up and Go (TUG) Test, 6-min walk test (6MWT), muscle strength, and knee range of motion were included. DATA EXTRACTION: Two researchers independently performed data extraction. Article data were extracted in Excel and summarized by a third researcher. DATA SYNTHESIS: The meta-analysis included 14 of the 1864 studies searched in the database. No statistical differences were found between the treatment and control groups in terms of WOMAC-stiffness (mean difference [MD]=-0.31, 95% confidence interval [CI] -0.64 to 0.03), TUG (MD=-0.17, 95% CI -0.71 to 0.38), 6MWT (MD=32.2, 95% CI -44.62 to 109.01), or muscle strength (standardized mean difference=0.24, 95% CI -0.02 to 0.50). However, statistically significant differences were found for WOMAC-total (MD=-6.83, 95% CI -12.3 to -1.37), WOMAC-pain (MD=-2.03, 95% CI -4.06 to -0.01), WOMAC-function (MD=-5.03, 95% CI -9.11 to -0.96), visual analog scale/numeric pain rating scale (MD=-1.24, 95% CI -2.43 to -0.06), and knee range of motion (MD=1.47, 95% CI 0.07 to 2.88). CONCLUSIONS: In older adults who exercise regularly, PBMT can potentially provide additional pain relief, improve knee joint function, and increase knee joint range of motion.

Age-related changes in adipose tissue metabolomics and inflammation, cardiolipin metabolism, and ferroptosis markers in female aged rat model.

Aging adipose tissue exhibits elevated inflammation and oxidative stress that are major sources of age-related metabolic dysfunction. However, the exact metabolic changes associated with inflammation and oxidative stress are unclear. To address this topic, we assessed variation in metabolic phenotypes of adipose tissue from 18 months adult sedentary (ASED), 26 months old sedentary (OSED), and 8 months young sedentary (YSED). The results of metabolomic analysis showed that ASED and OSED group had higher palmitic acid, elaidic acid, 1-heptadecanol, and α-tocopherol levels than YSED, but lower sarcosine levels. Furthermore, stearic acid was specifically elevated in ASED compared with YSED. Cholesterol was upregulated specifically in the OSED group compared with YSED, whereas linoleic acid was downregulated. In addition, ASED and OSED had more inflammatory cytokines, lower antioxidant capacity, and higher expression of ferroptosis-related genes than YSED. Moreover, mitochondrial dysfunction associated with abnormal cardiolipin synthesis was more pronounced in the OSED group. In conclusion, both ASED and OSED can affect the FA metabolism and increase oxidative stress in adipose tissue, leading to inflammation. In particular, linoleic acid content specifically decreases in OSED, which associated with abnormal cardiolipin synthesis and mitochondrial dysfunction in adipose tissue.

Long-term detraining reverses the improvement of lifelong exercise on skeletal muscle ferroptosis and inflammation in aging rats: fiber-type dependence of the Keap1/Nrf2 pathway.

We investigated the effects of lifelong aerobic exercise and 8 months of detraining after 10 months of aerobic training on circulation, skeletal muscle oxidative stress, and inflammation in aging rats. Sprague-Dawley rats were randomly assigned to the control (CON), detraining (DET), and lifelong aerobic training (LAT) groups. The DET and LAT groups began aerobic treadmill exercise at the age of 8 months and stopped training at the 18th and 26th month, respectively; all rats were sacrificed when aged 26 months. Compared with CON, LAT remarkably decreased serum and aged skeletal muscle 4-hydroxynonenal (4-HNE) and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. Superoxide dismutase 2(SOD2) levels were higher in the LAT group than in the CON group in skeletal muscle. However, DET remarkably decreased SOD2 protein expression and content in the skeletal muscle and increased malondialdehyde (MDA) level compared with LAT. Compared with LAT, DET remarkably downregulated adiponectin and upregulated tumor necrosis factor alpha (TNF-α) expression, while phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and 70-kDa ribosomal protein S6 kinase (P70S6K) protein expression decreased, and that of FoxO1 and muscle atrophy F-box (MAFbX) proteins increased in the quadriceps femoris. Adiponectin and TNF-α expression in the soleus muscle did not change between groups, whereas that of AKT, mammalian target of rapamycin (mTOR), and P70S6K was lower in the soleus in the DET group than in that in the LAT group. Compared with that in the LAT group, sestrin1 (SES1) and nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression in the DET group was lower, whereas Keap1 mRNA expression was remarkably upregulated in the quadriceps femoris. Interestingly, the protein and mRNA levels of SES1, Nrf2, and Keap1 in soleus muscle did not differ between groups. LAT remarkably upregulated ferritin heavy polypeptide 1(FTH), glutathione peroxidase 4(GPX4), and solute carrier family 7member 11 (SLC7A11) protein expression in the quadriceps femoris and soleus muscles, compared with CON. However, compared with LAT, DET downregulated FTH, GPX4, and SLC7A11 protein expression in the quadriceps femoris and soleus muscles. Long-term detraining during the aging phase reverses the improvement effect of lifelong exercise on oxidative stress, inflammation, ferroptosis, and muscle atrophy in aging skeletal muscle. The quadriceps femoris is more evident than the soleus, which may be related to the different changes in the Keap1/Nrf2 pathway in different skeletal muscles.

Indirect regulation of HIPPO pathway by miRNA mediates high-intensity intermittent exercise to ameliorate aging skeletal muscle function.

Exercise-induced microRNA (miRNA) and HIPPO pathways participate in the regulation of skeletal muscle plasticity but their underlying mechanisms remain unclear. We aimed to investigate the effect of high-intensity interval training (HIIT) on miRNA expression and the HIPPO pathway in the skeletal muscle of aging rats to determine its role in the amelioration of muscle aging. Thirty-six 18-month-old female rats were randomly divided into sedentary control (SED, n = 12), moderate-intensity continuous training (MICT, n = 12), and HIIT (n = 12) groups, with continuous exercise for 8 months. Quantitative reverse transcription-polymerase chain reaction, immunoblotting, KEGG enrichment, and dual-luciferase assays were performed on the target skeletal muscle. Compared with the SED group, the MICT and HIIT groups showed a significant trend of improvement in Lee's index and grip strength and a marked increase in skeletal muscle mitochondrial function, apoptosis, antioxidant, and lipolysis-related protein expression. They also exhibited PI3K/AKT pathway activation and a decrease in expression of HIPPO pathway-related proteins; 20 miRNAs were differentially expressed and enriched in the exercise group compared with the SED group, including the HIPPO pathway and metabolic pathways. Further analysis of L6 cells confirmed that miR-182 may target PTEN, which indirectly regulates HIPPO signaling, but not Mob1. the combined application of HIIT and MICT increased the antioxidant and lipolytic capacities of skeletal muscle and improved atrophy of aging skeletal muscle; HIIT was more effective than MICT. This may be related to HIIT-mediated AKT pathway activation and HIPPO pathway inhibition by miRNAs (miR-486 and miR-182).

Effects of Dietary Riboflavin Supplementation on the Growth Performance, Body Composition and Anti-Oxidative Capacity of Coho Salmon (Oncorhynchus kisutch) Post-Smolts.

The present study investigated the effects of dietary riboflavin on growth performance, body composition and anti-oxidative capacity of coho salmon (Oncorhynchus kisutch) post-smolts. Seven experimental diets were formulated with graded riboflavin levels of 0.00, 3.96, 8.07, 16.11, 31.81, 63.67 and 126.69 mg/kg, respectively. Each diet was fed to triplicate groups of 10 fish with an individually initial mean body weight of 186.22 ± 0.41 g in 21 cages (water volume, 1000-L/cage) and fed three times daily (7:30, 12:30 and 17:30) to apparent satiation for 12 weeks. Fish fed a diet with 31.81 mg/kg riboflavin had the highest specific growth rate (SGR), which was significantly higher than fish-fed diets with 0.00, 3.96, 8.07 and 126.69 mg/kg riboflavin (p < 0.05). Feed conversion ratio showed an inverse trend with SGR. No significant differences were observed in condition factor, hepatosomatic index, viscerosomatic index, muscle moisture, crude protein and ash contents among dietary groups. Muscle lipid had the highest content in the 31.81 mg/kg group and was significantly higher (p < 0.05) than those in the 0.00, 3.96 and 8.07 mg/kg groups. The alanine aminotransferase, aspartate aminotransferase and malondialdehyde contents in the liver and serum of fish were significantly decreased with the increase in dietary riboflavin level up to 31.81 mg/kg, and then increased as dietary riboflavin level further increased. An inverse trend was observed for total superoxide dismutase and catalase activities. Serum total cholesterol and triglyceride levels were significantly decreased with the dietary of riboflavin levels up to 31.81 and 63.67 mg/kg, respectively. The cubic curve regression analysis based on SGR indicated that the optimum dietary riboflavin level was estimated to be 35.26 mg/kg for coho salmon post-smolts.

Large Room Temperature Magnetization Enhancement in a Copper-Based Photoactive Metal-Organic Framework.

The tris(pyridin-4-yl)amine ligand was found to exhibit a radical-actuated coloration phenomenon, and a novel copper-based color-changeable metal-organic framework (MOF) was synthesized via this photoactive ligand. After light irradiation, the photogenerated stable radicals in this framework induced increasing amplitude of magnetization (32%) at room temperature, being the largest enhancement among radical-based photochromic systems.

Lifelong Exercise in Age Rats Improves Skeletal Muscle Function and MicroRNA Profile.

PURPOSE: Lifelong exercise is known to attenuate sarcopenia (age-associated reduction in muscle mass and function); however, the underlying molecular mechanisms remain unclear. As microRNAs are widely involved in the regulation of skeletal muscle growth and development, we aimed to evaluate the effects of lifelong regular exercise on age-related alterations in muscle microRNA expression profiles as well as on skeletal muscle atrophy, apoptosis, and mitochondria and autophagy dysfunction. METHODS: Female 8-month-old Sprague-Dawley rats were divided into four groups; 1) 18 months of moderate-intensity continuous training (MICT) initiated at 8 months (adult-MICT, n = 12), 2) 8 months of MICT initiated at 18 months (presarcopenia-MICT, n = 12), 3) 8-month-old adult sedentary controls (adult-SED), and 4) 26-month-old aging sedentary controls (old-SED). Age skeletal muscles were then subjected to quantitative reverse transcription-polymerase chain reaction, Kyoto Encyclopedia of Genes and Genomes, immunoblotting, and miR-486 3' untranslated region luciferase reporter gene analyses. RESULTS: Age-related loss of miR-486 expression was improved, skeletal muscle atrophy and apoptosis were downregulated, and mitochondrial activity and autophagy were upregulated in the adult-MICT group. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the PI3K/Akt pathway was upregulated in adult-MICT rats compared with that in old-SED. In vitro analyses in rat skeletal muscle L6 cells further confirmed that miR-486 targets PTEN, not SAV1, thereby activating the PI3K/Akt pathway and indirectly inhibiting HIPPO signaling. CONCLUSIONS: Compared with presarcopenia-MICT rats, adult-MICT rats experienced greater beneficial effects regarding ameliorated age-related alterations in muscle miRNA expression profile, skeletal muscle atrophy, apoptosis, and mitochondria and autophagy dysfunction, which is potentially associated with the increased miR-486 expression and concomitant targeting of the PTEN/Akt signaling pathway.

Alterations in mitochondrial biogenesis and respiratory activity, inflammation of the senescence-associated secretory phenotype, and lipolysis in the perirenal fat and liver of rats following lifelong exercise and detraining.

The primary aims of this study were to determine the effects of lifelong exercise and detraining on age-related alterations in mitochondrial function, inflammation associated with senescence-associated secretory phenotype (SASP), and lipolysis in the perirenal fat and liver of rats. Female Sprague-Dawley rats were randomly assigned to four groups: young control (n = 12), old control (n = 12), detraining (n = 12), and lifelong exercise (n = 12). We then investigated mitochondrial function, SASP-associated inflammation, and lipolysis in the perirenal fat and liver using qRT-PCR and western blotting to assess the expression of AKT, hypoxia-inducible factor 1α (HIF-1α), nuclear factor-kappa B (NF-κB), c-jun kinase (JNK), and p38 mitogen-activated protein kinase (p38MAPK). In the tissues of both the perirenal fat and liver, lifelong exercise significantly improved mitochondrial function, SASP-associated inflammation, and lipolysis. Meanwhile, pathways associated with inflammatory regulation were inhibited, predominantly via the activation of phosphorylated-AKT (p-AKT) and suppression of HIF-1α in both tissues, and via JNK in the perirenal fat and p38MAPK in the liver. Furthermore, detraining activated NF-κB expression in both tissues and induced the upregulation of serum high-sensitivity C-reactive protein (hsCRP) levels. Collectively, lifelong exercise was found to exert beneficial effects by ameliorating age-related alterations in mitochondrial function, SASP-associated inflammation, and lipolysis in perirenal fat and liver tissues, potentially inhibiting inflammation via the JNK and p38 MAPK pathways, respectively, as well as the HIF-1α and AKT pathways in both tissues. In contrast, detraining induced high levels of circulating hsCRP by activating the NF-κB signaling pathway in both tissues.

Impact of high-intensity interval training on cardiorespiratory fitness, body composition, physical fitness, and metabolic parameters in older adults: A meta-analysis of randomized controlled trials.

High-intensity interval training (HIIT) can effectively increase peak oxygen consumption, body composition, physical fitness, and health-related characteristics of adults; however, its impact in the older population remains highly debated. This review and meta-analysis aimed to evaluate the effects of high-intensity interval training on cardiorespiratory fitness, body composition, physical fitness, and health-related outcomes in older adults. Four electronic databases (PubMed, Scopus, Medline, and Web of Science) were searched (until July 2020) for randomized trials comparing the effect of HIIT on physical fitness, metabolic parameters, and cardiorespiratory fitness in older adults. The Cochrane risk of bias assessment tool was used to evaluate the methodological quality of the included studies; Stata 14.0 software was used for statistical analysis. HIIT significantly improved the maximum rate of oxygen consumption (VO2peak) as compared to a moderate-intensity continuous training (MICT) protocol (HIIT vs. MICT: weighted mean difference = 1.74, 95% confidence interval: 0.80-2.69, p < 0.001). Additional subgroup analyses determined that training periods >12 weeks, training frequencies of 2 sessions/week, session lengths of 40 min, 6 sets and repetitions, training times per repetition of >60 s, and rest times of <90 s were more effective for VO2peak. This systematic review and meta-analysis showed that HIIT induces favorable adaptions in cardiorespiratory fitness, physical fitness, muscle power, cardiac contractile function, mitochondrial citrate synthase activity, and reduced blood triglyceride and glucose levels in older individuals, which may help to maintain aerobic fitness and slow down the process of sarcopenia.

Synthesis of organoselenyl isoquinolinium imides via iron(III) chloride-mediated tandem cyclization/selenation of N'-(2-alkynylbenzylidene)hydrazides and diselenides.

This report describes the synthesis of organoselenyl isoquinolinium imides through a tandem cyclization between N'-(2-alkynylbenzylidene)hydrazides and diselenides. The reaction was carried out at room temperature under an ambient atmosphere using cheap iron(iii) chloride as the metallic source. The strategy shows good tolerance to a broad range of N'-(2-alkynylbenzylidene)hydrazides and diselenides, and forms C-N and C-Se bonds in one step. The obtained product is further transformed into a bioactive H-pyrazolo[5,1-a]isoquinoline skeleton easily via a silver catalyzed [3 + 2] cycloaddition.

Effects of lifelong exercise on age-related body composition, oxidative stress, inflammatory cytokines, and skeletal muscle proteome in rats.

PURPOSE: This study aims to evaluate whether regular lifelong exercise has effects on age-related inflammatory cytokines, oxidative stress, and the skeletal muscle proteome. METHODS: Four groups of adult-aged (8-month-old) female Sprague Dawley rats were used: rats for which training was initiated at either 8 (8 M-MICT, moderate-intensity continuous training) or 18 months (18 M-MICT) and sedentary rats aged either 26 (26 M-SED) or 8 months (8M-SED), who served as aging and adult sedentary controls, respectively. Aged skeletal muscles were subjected to proteomic and Kyoto Encyclopedia of Genes and Genomes (KEGG) and immunoblotting analyses. RESULTS: Age-related loss of physical performance and anti-inflammatory steroid levels were lowest in the 8 M-MICT group, while the anti-oxidative activities remained unchanged compared to 18 M-MICT rats. The proteomic analysis demonstrated an amelioration of age-related changes to muscle contraction, focal adhesion signaling, mitochondrial function, apoptosis and regeneration, anti-oxidation, and protein processing in the endoplasmic reticulum in the 8 M-MICT. Additionally, neurotrophin (BDNF) and AKT/FOXO signaling pathways were upregulated in 8 M-MICT rats compared to 26 M-SED. CONCLUSION: 8 M-MICT exhibited greater beneficial effects in ameliorating age-related inflammation and physical performance loss, compared to 18 M-MICT. The amelioration is potentially related to the upregulation of autophagy activities via BDNF/AKT signaling.

Relationships of accelerometer-based measured objective physical activity and sedentary behaviour with cognitive function: a comparative cross-sectional study of China's elderly population.

BACKGROUND: This study explored the effects of physical activity and sedentary behaviour on the decline of cognitive ability among the elderly. To compensate for the limitations of self-reported physical activity, objective measures were used. METHODS: A cross-sectional survey of 308 aged people mean 68.66 ± 5.377 years, in Nanjing, China, was conducted. Physical activity was measured using the ActiGraph GT3X+, and cognitive function was measured using the Montreal Cognitive Assessment. RESULTS: The overall participant model, adjusted for age, BMI, education, and monthly average income, found that light physical activity (ß = 0.006, p < 0.01), moderate-vigorous physical activity (ß = 0.068, p < 0.001), and total physical activity (ß = 0.006, p < 0.01) had a significant linear relationship with cognitive ability, while sedentary time did not (ß = - 0.020, p>0.05). Further, light physical activity only affects the cognitive ability of elderly females (ß = 0.006, p < 0.05). There was an inverted 'U' association between moderate-vigorous physical activity and cognitive ability. The association models found that moderate-vigorous physical activity in the 22.13 min·day- 1~38.79 min·day- 1 range affected cognitive ability most beneficially, with the highest beta coefficient among all groups (ß = 0.091, p < 0.05). CONCLUSIONS: While physical activity can significantly improve cognitive ability among the elderly, sedentary behaviour is associated with decreased cognitive function across genders.

Iron(iii) chloride-promoted cyclization of α,ß-alkynic tosylhydrazones with diselenides: synthesis of 4-(arylselanyl)-1H-pyrazoles.

A highly efficient iron(iii) chloride-promoted cyclization between α,ß-alkynic tosylhydrazones and diselenides to form a 4-(arylselanyl)-1H-pyrazole skeleton is studied. This reaction forms C-N and C-Se bonds in one step by utilizing inexpensive iron(iii) chloride instead of expensive transition metal additives. This strategy features easily synthesized substrates, mild reaction conditions and high tolerance to functional groups.

Effects of high-intensity interval training on adipose tissue lipolysis, inflammation, and metabolomics in aged rats.

High-intensity interval training (HIIT) is a time-efficient alternative to moderate-intensity continuous training (MICT) to improve metabolic health in older individuals. However, differences in adipose tissue metabolism between these two approaches are unclear. Here, we evaluated the effects of HIIT and MICT on metabolic phenotypes in aged rats. HIIT significantly decreased fat mass, increased percent lean mass, decreased fat-to-lean ratio, reduced serum high-sensitivity C-reactive protein, increased serum interleukin-10 levels, and decreased perirenal adipose tissue leptin compared with rats in the sedentary (SED) group. HIIT also increased pregnenolone, cortisol, and corticosterone in both adipose tissue and serum. Both exercise modalities enhanced hormone-sensitive lipase and adipose triglyceride lipase expression compared with the SED group and decreased palmitic acid, stearic acid, octadecadienoic acid, urea, 1-heptadecanol, and α-tocopherol. MICT was related to glycerolipid metabolism, whereas HIIT was related to steroid hormone biosynthesis. Overall, HIIT showed more favorable regulation of anti-inflammatory activity than MICT.

Influence of the built environment of Nanjing's Urban Community on the leisure physical activity of the elderly: an empirical study.

BACKGROUND: Urbanization and aging are global phenomena that offer unique challenges in different countries. A supportive environment plays an important role in addressing the issues of health behavioral change and health promotion (e.g., prevent chronic illnesses, promote mental health) among older adults. With the development of the socio-ecological theoretical model, studies on the impact of supportive environments on physical activity have become popular in the public health field in the EU and US. Meanwhile, very few Chinese studies have examined the relationship between built environment features and older adults' physical activity at the ecological level. The purpose of the study is to investigate how the factors part of the built environment of Nanjing's communities also influence leisure time physical activity among the elderly. METHODS: Using a socio-ecological model as a theoretical framework, we conducted a cross-sectional study of 399 elderly people from 19 communities in Nanjing, China, using a one-on-one questionnaire to collect data, including participants' perceived built environment and self-reported physical activity. A multivariate linear regression method was used to analyze the factors influencing their recreational physical activity. RESULTS: This study found that compared to older people with low average monthly income, the recreational physical activity of the elderly with average monthly incomes between 1001 and 2000 ¥ (ß = 23.31, p < 0.001) and 2001 ¥ or more (ß = 21.15, p < 0.001) are significantly higher. After controlling for individual covariates, street connectivity (ß = 7.34, p = 0.030) and street pavement slope (ß = - 7.72, p = 0.020), we found that two out of ten built environment factors indicators influence their physical activity. The importance of each influencing factor ranked from highest to lowest are monthly average income, street pavement slope, and street connectivity. Other factors were not significantly related to recreational physical activity by the elderly. CONCLUSIONS: Older adults with a high income were more likely to participate in recreational physical activity than those with a low income. In order to positively impact physical activity in older adults and ultimately improve health, policymakers and urban planners need to ensure that street connectivity and street pavement slope are factored into the design and development of the urban environment.

Proteomics-based identification of different training adaptations of aged skeletal muscle following long-term high-intensity interval and moderate-intensity continuous training in aged rats.

Aging-associated loss of skeletal muscle mass and force increases the risk of falls, impairs mobility, and leads to a reduced quality of life. High-intensity interval training (HIIT) is superior to moderate-intensity continuous training (MICT) for improving morphological and metabolic adaptations of skeletal muscle in older adults, but the underlying mechanism is unknown. Aged female rats underwent HIIT and MICT for 8 months, and their differential impacts on skeletal muscle proteome were investigated. HIIT resulted in a larger improvement in grip strength and fiber cross-sectional area, with similar increases in inclined plane performance and time to exhaustion. Proteomic analysis showed that common training adaptations of both protocols included changes to muscle contraction, focal adhesion signaling, mitochondrial function, apoptosis and regeneration, and anti-oxidation, whereas protein processing in the endoplasmic reticulum and adipocytokine signaling were specifically altered in the MICT and HIIT groups, respectively. Immunoblotting showed that upregulation of the adiponectin/AMPK signaling pathway may be associated with improvements in autophagy, oxidative stress, mitochondrial function, and apoptosis in aged skeletal muscle following HIIT. Thus, understanding the molecular differences in training adaptations from these two exercise modalities may aid in combatting sarcopenia.

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.

Beneficial Autophagic Activities, Mitochondrial Function, and Metabolic Phenotype Adaptations Promoted by High-Intensity Interval Training in a Rat Model.

The effects of high-intensity interval (HIIT) and moderate-intensity continuous training (MICT) on basal autophagy and mitochondrial function in cardiac and skeletal muscle and plasma metabolic phenotypes have not been clearly characterized. Here, we investigated how 10-weeks HIIT and MICT differentially modify basal autophagy and mitochondrial markers in cardiac and skeletal muscle and conducted an untargeted metabolomics study with proton nuclear magnetic resonance (1H NMR) spectroscopy and multivariate statistical analysis of plasma metabolic phenotypes. Male Sprague-Dawley rats were separated into three groups: sedentary control (SED), MICT, and HIIT. Rats underwent evaluation of exercise performance, including exercise tolerance and grip strength, and blood lactate levels were measured immediately after an incremental exercise test. Plasma samples were analyzed by 1H NMR. The expression of autophagy and mitochondrial markers and autophagic flux (LC3II/LC3-I ratio) in cardiac, rectus femoris, and soleus muscle were analyzed by western blotting. Time to exhaustion and grip strength increased significantly following HIIT compared with that in both SED and MICT groups. Compared with those in the SED group, blood lactate level, and the expression of SDH, COX-IV, and SIRT3 significantly increased in rectus femoris and soleus muscle of both HIIT and MICT groups. Meanwhile, SDH and COX-IV content of cardiac muscle and COX-IV and SIRT3 content of rectus femoris and soleus muscle increased significantly following HIIT compared with that following MICT. The expression of LC3-II, ATG-3, and Beclin-1 and LC3II/LC3-I ratio were significantly increased only in soleus and cardiac muscle following HIIT. These data indicate that HIIT was more effective for improving physical performance and facilitating cardiac and skeletal muscle adaptations that increase mitochondrial function and basal autophagic activities. Moreover, 1H NMR spectroscopy and multivariate statistical analysis identified 11 metabolites in plasma, among which fine significantly and similarly changed after both HIIT and MICT, while BCAAs isoleucine, leucine, and valine and glutamine were changed only after HIIT. Together, these data indicate distinct differences in specific metabolites and autophagy and mitochondrial markers following HIIT vs. MICT and highlight the value of metabolomic analysis in providing more detailed insight into the metabolic adaptations to exercise training.

Cardiac basal autophagic activity and increased exercise capacity.

To investigate whether high-intensity interval training (HIIT) and continuous moderate-intensity training (CMT) have different impacts on exercise performance and cardiac function and to determine the influence of these exercise protocols on modulating basal autophagy in the cardiac muscle of rats. Rats were assigned to three groups: sedentary control (SC), CMT, and HIIT. Total exercise volume and mean intensity were matched between the two protocols. After a 10-week training program, rats were evaluated for exercise performance, including exercise tolerance and grip strength. Blood lactate levels were measured after an incremental exercise test. Cardiac function and morphology were assessed by echocardiography. Western blotting was used to evaluate the expression of autophagy and mitochondrial markers. Transmission electron microscopy was used to evaluate mitochondrial content. The results showed that time to exhaustion and grip strength increased significantly in the HIIT group compared with the SC and CMT groups. Both training interventions significantly increased time to exhaustion, reduced blood lactate level (after an incremental exercise test) and induced adaptive changes in cardiac morphology, but without altering cardiac systolic function. The greater improvements in exercise performance with the HIIT than with the CMT protocol were related to improvement in basal autophagic adaptation and mitochondria function in cardiac muscle. Mitochondria markers were positively correlated with autophagy makers. This study shows that HIIT is more effective for improving exercise performance than CMT and this improvement is related to mitochondrial function and basal autophagic adaptation in cardiac muscle.