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.

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.

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.