Sarcopenia has been defined as a progressive decline of skeletal muscle mass, strength, and functions in elderly people. It is accompanied by physical frailty, functional disability, falls, hospitalization, and mortality, and is becoming a major geriatric disorder owing to the increasing life expectancy and growing older population worldwide. Experimental models are critical to understand the pathophysiology of sarcopenia and develop therapeutic strategies. Although its etiologies remain to be further elucidated, several mechanisms of sarcopenia have been identified, including cellular senescence, proteostasis imbalance, oxidative stress, and “inflammaging.” In this article, we address three main aspects. First, we describe the fundamental aging mechanisms. Next, we discuss both in vitro and in vivo experimental models based on molecular mechanisms that have the potential to elucidate the biochemical processes integral to sarcopenia. The use of appropriate models to reflect sarcopenia and/or its underlying pathways will enable researchers to understand sarcopenia and develop novel therapeutic strategies for sarcopenia. Lastly, we discuss the possible molecular targets and the current status of drug candidates for sarcopenia treatment. In conclusion, the development of experimental models for sarcopenia is essential to discover molecular targets that are valuable as biochemical biomarkers and/or therapeutic targets for sarcopenia.

Although Alzheimer’s disease (AD)-like pathology is frequently found in patients with post-stroke dementia, little is known about the effects of aerobic exercise on the modifications of tau and related proteins. Therefore, we evaluated the effects of aerobic exercise on the phosphorylation and acetylation of tau and the expressions of tau-related proteins, after middle cerebral artery occlusion (MCAO) stroke. Twenty-four Sprague–Dawley rats with MCAO infarction were used in this study. The rehabilitation group (RG) received treadmill training 40 min/day for 12 weeks, whereas the sedentary group (SG) did not receive any type of training. Functional tests, such as the single pellet reaching task, rotarod, and radial arm maze tests, were performed monthly for 3 months. In ipsilateral cortices in the RG and SG groups, level of Ac-tau was lower in the RG, whereas levels of p-tauS396, p-tauS262, and p-tauS202/T205 were not significantly lower in the RG. Level of phosphorylated glycogen synthase kinase 3-beta Tyr 216 (p-GSK3βY216) was lower in the RG, but levels of p-AMPK and phosphorylated glycogen synthase kinase 3-beta Ser 9 (p-GSK3βS9) were not significantly lower. Levels of COX-2 and BDNF were not significantly different between the two groups, while SIRT1 significantly decreased in ipsilateral cortices in RG. In addition, aerobic training also improved motor, balance, and memory functions. Rehabilitation with aerobic exercise inhibited tau modification, especially tau acetylation, following infarction in the rat MCAO model, which was accompanied with the improvement of motor and cognitive functions.

Sarcopenia, a syndrome commonly seen in elderly populations, is often characterized by a gradual loss of skeletal muscle, leading to the decline of muscle strength and physical performance. Growing evidence suggests that the prevalence of sarcopenia increases in patients with heart failure (HF), which is a dominant pathogenesis in the aging heart. HF causes diverse metabolic complications that may result in sarcopenia. Therefore, sarcopenia may act as a strong predictor of frailty, disability, and mortality associated with HF. Currently, standard treatments for slowing muscle loss in patients with HF are not available. Therefore, here, we review the pathophysiological mechanisms underlying sarcopenia in HF as well as current knowledge regarding the beneficial effects of exercise on sarcopenia in HF and related mechanisms, including hormonal changes, myostatin, oxidative stress, inflammation, apoptosis, autophagy, the ubiquitin-proteasome system, and insulin resistance.

Exosome-like extracellular vesicles (ELVs) contain biomolecules that have potential as diagnostic biomarkers, such as proteins, micro-RNAs (miRNAs), and lipids. However, it is difficult to enrich ELVs consistently with high yield and purity from clinical samples, which hampers the development of ELV biomarkers. This is particularly true for miRNAs in protein-rich plasma. Hence, we modified ELV isolation protocols of three commercially available polymer-precipitation-based kits using proteinase K (PK) treatment to quantify ELV-associated miRNAs in human plasma. We compared the yield, purity, and characteristics of enriched plasma ELVs, and measured the relative quantity of three selected miRNAs (miR-30c, miR-126, and miR-192) in ELVs using six human plasma samples. Compared with the original protocols, we demonstrated that ELVs can be isolated with PK treatment with high purity (i.e., lack of non-exosomal proteins and homogeneous size of vesicles) and yield (i.e., abundancy of exosomal markers), which were dependent on kits. Using the kit with the highest purity and yield with PK treatment, we successfully quantified ELV miRNAs (levels of 45%–65% in total plasma) with acceptable variability. Collectively, ELV enrichment using the modified easy-to-use method appears suitable for the analysis of miRNAs, although its clinical applicability needs to be confirmed in larger clinical studies.

In the 115 years since the discovery of Alzheimer’s disease (AD), our knowledge, diagnosis, and therapeutics have significantly improved. Biomarkers are the primary tools for clinical research, diagnostics, and therapeutic monitoring in clinical trials. They provide much insightful information, and while they are not clinically used routinely, they help us to understand the mechanisms of this disease. This review charts the journey of AD biomarker discovery and development from cerebrospinal fluid (CSF) amyloid-beta 1-42 (Aβ42), total tau (T-tau), and phosphorylated tau (p-tau) biomarkers and imaging technologies to the next generation of biomarkers. We also discuss advanced high-sensitivity assay platforms for CSF Aβ42, T-tau, p-tau, and blood analysis. The recently proposed Aβ deposition/tau biomarker/neurodegeneration or neuronal injury (ATN) scheme might facilitate the definition of the biological status underpinning AD and offer a common language among researchers across biochemical biomarkers and imaging. Moreover, we highlight blood-based biomarkers for AD that offer a scalable alternative to CSF biomarkers through cost-saving and reduced invasiveness, and may provide an understanding of disease initiation and development. We discuss different groups of blood-based biomarker candidates, their advantages and limitations, and paths forward, from identification and analysis to clinical validation. The development of valid blood-based biomarkers may facilitate the implementation of future AD therapeutics and diagnostics.