No abstract

Older individuals have a reduced capacity to induce muscle hypertrophy with resistance exercise (RE), which may contribute to the age-induced loss of muscle mass and function, sarcopenia. We tested the novel hypothesis that dysregulation of microRNAs (miRNAs) may contribute to reduced muscle plasticity with aging. Skeletal muscle expression profiling of protein-coding genes and miRNA was performed in younger (YNG) and older (OLD) men after an acute bout of RE. 21 miRNAs were altered by RE in YNG men, while no RE-induced changes in miRNA expression were observed in OLD men. This striking absence in miRNA regulation in OLD men was associated with blunted transcription of mRNAs, with only 42 genes altered in OLD men vs. 175 in YNG men following RE, demonstrating a reduced adaptability of aging muscle to exercise. Integrated bioinformatics analysis identified miR-126 as an important regulator of the transcriptional response to exercise and reduced lean mass in OLD men. Manipulation of miR-126 levels in myocytes, in vitro, revealed its direct effects on the expression of regulators of skeletal muscle growth and activation of insulin growth factor 1 (IGF-1) signaling. This work identifies a mechanistic role of miRNA in the adaptation of muscle to anabolic stimulation and reveals a significant impairment in exercise-induced miRNA/mRNA regulation with aging.

The loss of skeletal muscle mass is observed in many pathophysiological conditions, including aging and obesity. The loss of muscle mass and function with aging is defined as sarcopenia and is characterized by a mismatch between skeletal muscle protein synthesis and breakdown. Characteristic metabolic features of both aging and obesity are increases in intramyocellular lipid (IMCL) content in muscle. IMCL accumulation may play a mechanistic role in the development of anabolic resistance and the progression of muscle atrophy in aging and obesity. In the present study, aged and high-fat fed mice were used to determine mechanisms leading to muscle loss. We hypothesized the accumulation of bioactive lipids in skeletal muscle, such as ceramide or diacylglycerols, leads to insulin resistance with aging and obesity and the inability to activate protein synthesis, contributing to skeletal muscle loss. We report a positive association between bioactive lipid accumulation and the loss of lean mass and muscle strength. Obese and aged animals had significantly higher storage of ceramide and diacylglycerol compared with young. Furthermore, there was an attenuated insulin response in components of the mTOR anabolic signaling pathway. We also observed differential increases in the expression of inflammatory cytokines and the phosphorylation of IκBα with aging and obesity. These data challenge the accepted role of increased inflammation in obesity-induced insulin resistance in skeletal muscle. Furthermore, we have now established IκBα with a novel function in aging-associated muscle loss that may be independent of its previously understood role as an NF-κB inhibitor.

Highlights d Adaptive evolution produces a dominant-negative allele of the piRNA gene cuff d Cutoff balances interlinked canonical and non-canonical piRNA cluster transcription d CtBP suppresses canonical transcription of both piRNA clusters and transposons

Self-healing rebar coatings were prepared and investigated for steel-reinforced concrete, with the goal of creating coatings that can withstand construction site damage. Such damage to conventional coatings results in epoxy chipping or cracking and negates the coatings’ ability to resist corrosion. The coatings consisted of a conventional epoxy coating containing 10 wt % microencapsulated tung oil as the healing agent. Upon coating damage, the microcapsules ruptured, releasing tung oil that cured across the damaged area. In accelerated corrosion testing, the times to failure of steel-reinforced concrete with self-healing coatings were at least three times longer than steel-reinforced concrete with conventional coatings. After 150 days of accelerated corrosion testing, 83% of the samples with self-healing coatings exhibited no corrosion. No difference between undamaged and intentionally damaged specimens was observed, potentially because the damaged area was not large enough. These results suggest that natural product-based, self-healing coatings are able to passivate rebar surfaces in response to corrosion initiation, significantly increasing their corrosion protection ability. Pullout testing revealed that self-healing coatings exhibited comparable bond stresses compared to conventional coatings. In summary, this is a promising technology for extending service lives of steel-reinforced concrete structures with no reduction in interfacial bonding, which could have significant implications for infrastructure resilience and CO2 emissions.