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.

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.

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.

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.

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.