Neuromuscular Dysfunction Precedes Cognitive Impairment in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) develops along a continuum that spans years prior to diagnosis. Decreased muscle function and mitochondrial respiration occur years earlier in those that develop AD; however, it is unknown what causes these peripheral phenotypes in a disease of the brain. Exercise promotes muscle, mitochondria, and cognitive health and is proposed to be a potential therapeutic for AD, but no study has investigated how skeletal muscle adapts to exercise training in an AD-like context. Utilizing 5xFAD mice, an AD model that develops ad-like pathology and cognitive impairments around 6 mo of age, we examined in vivo neuromuscular function and exercise adapations (mitochondrial respiration and RNA sequencing) before the manifestation of overt cognitive impairment. We found 5xFAD mice develop neuromuscular dysfunction beginning as early as 4 mo of age, characterized by impaired nerve-stimulated muscle torque production and compound nerve action potential of the sciatic nerve. Furthermore, skeletal muscle in 5xFAD mice had altered, sex-dependent, adaptive responses (mitochondrial respiration and gene expression) to exercise training in the absence of overt cognitive impairment. Changes in peripheral systems, specifically neural communication to skeletal muscle, may be harbingers for AD and have implications for lifestyle interventions, like exercise, in AD.

Effects of resistance training on muscle strength, insulin-like growth factor-1, and insulin-like growth factor-binding protein-3 in healthy elderly subjects: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Findings regarding the effects of resistance training (RT) on muscle strength, serum level of IGF-1, and its binding proteins are contradictory. To resolve this contradiction, we performed a systematic review and meta-analysis to investigate the effects of RT on muscle strength, the levels of serum IGF-1, and IGF-binding protein-3 in the elderly and aged. MATERIALS AND METHODS: The PubMed, CINAHL, Medline, Google Scholar, and Scopus databases and reference lists of included studies were systematically searched to identify randomized controlled trials (RCTs) comparing subjects who underwent RT and control individuals up to May 15, 2020. This study was performed following the Preferred Items for Reporting of Systematic Reviews and Meta-Analyses guidelines. We identified and analyzed 11 eligible trials in this meta-analysis. RESULTS: Pooled data displayed an overall significant elevation in IGF-1 (mean difference (MD): 17.34 ng/ml; 95% confidence interval (CI): 7.23, 27.46) and in muscle strength in leg press (SMD: 0.82; 95% CI: 0.30, 1.34) and bench press (SMD: 0.82; 95% CI: 0.42, 1.23) following RT. By contrast, the pooled estimate showed a non-significant elevation in IGFBP-3 (MD: 0.13 ng/ml; 95% CI: - 39.39, 39.65). Subgroup analysis revealed that the elevation in serum IGF-1 levels after RT was significant only in women (MD: 19.30 ng/ml); moreover, it increased after intervention durations of both > 12 weeks (MD: 21.98 ng/ml) and of ≤ 12 weeks (MD: 15.31 ng/ml). CONCLUSION: RT was associated with elevated muscle strength. Moreover, RT was correlated with increased serum levels of IGF-1 among women and among those who received the training for ≤ 12 weeks or > 12 weeks. Further studies are required to elucidate the mechanisms underlying the impact of RT on IGF-1, IGFBP-3, and muscle strength.

The aesthetic values of silence and its impacts on romanticism and contemporary artists.

In our modern world, where people suffer from self-alienation and are after the meaning of existence in their mechanical and flamboyant outside world, finding a discernible language is very important. People's dejected minds are the products of miserable modern societies that have changed them into taciturn and uncommunicative creatures in search of meaning. The significance of language, specifically poetic or living language, is undeniable in different eras. Therefore, it would be easier for artists to communicate with people by letting them get the maximum meaning with the least amount of words. This is something that happens in the discourse of modern people. This article shows the aesthetic values of silence and its impacts on romantic and contemporary artists, who for us here will be represented by Samuel Taylor Coleridge as a romantic artist versus Harold Pinter as a contemporary dramatist.