Current Protein and Peptide Science - Volume 19, Issue 7, 2018

Sarcopenia, the progressive and generalized loss of skeletal muscle mass and strength/function associated with aging, increases the risk of a vast array of adverse health outcomes, including falls, morbidity, loss of independence, disability, and mortality. As such, sarcopenia poses a huge socioeconomic burden in developed countries. The development and implementation of effective interventions against sarcopenia are therefore a public health priority. A preliminary, fundamental step in such a process entails the agreement of researchers, healthcare professionals and policymakers around a unique operational definition of sarcopenia. This will facilitate the framing of a clear clinical entity to be incorporated in standard practice, the understanding of the underlying pathophysiology, and the identification of biological targets for drug development.

Sarcopenia, the progressive and generalized loss of muscle mass and strength/function, is a major health issue in older adults, given its high prevalence and burdensome clinical ramifications. The absence of a unified operational definition for sarcopenia has hampered its full appreciation by healthcare providers, researchers and policy-makers. At the same time, this unresolved debate and the complexity of musculoskeletal aging pose major challenges to the identification of clinically meaningful biomarkers. This review summarizes the current knowledge on biological markers for sarcopenia, including a critical appraisal of traditional procedures for biomarker development in the field of muscle aging. As an alternative approach, we illustrate the potential advantages of biomarker discovery procedures based on multivariate methodologies. Relevant examples of multidimensional biomarker modeling are provided with an emphasis on its clinical and research application.

According to the free-radical theory of aging, oxidative stress is a key contributor to the onset of age-related conditions by inducing structural and functional alterations in several cellular components. Although innate defenses exist for limiting the occurrence of such detrimental effects, their ability to counteract the continuous and large production of reactive oxygen species becomes increasingly inefficient with aging. In this context, interventions aimed at preserving the homeostatic balance between oxidant production and antioxidant protection may be beneficial on the pathophysiological modifications and clinical manifestations featuring the aging process. Sarcopenia is a clinical condition defined as the progressive age-related loss of muscle mass and function. In particular, a reduction of motor units and wasting of muscle fibers occurs during the aging process and negatively affects muscle quality. The biological mechanisms responsible for sarcopenia are complex, multifactorial and closely related to those characterizing the aging process. Among these, a pronounced unbalance between pro-oxidant and antioxidant species may play a major role. This review paper presents and discusses the possible role of the oxidant/antioxidant systems in the determination and development of the sarcopenic phenotype. Special attention will be devoted to the contribution of antioxidant agents in the maintenance of the homeostatic equilibrium for the organismal protection against the onset of age-related conditions. However, despite their popularity as beneficial compounds, there is no clear evidence in the literature about the protective effect of antioxidant supplements usage. Therefore, further research is needed to address and clarify such ambiguity.

Sarcopenia is a debilitating condition that involves loss of muscle mass and function, which affects virtually everyone as they age, and can lead to frailty and ultimately disability. In growing recognition of the importance of both muscle strength and muscle mass relative to body size in contributing to functional decline, recent definitions have now incorporated grip strength and a correction for body mass as part of the key criteria that define sarcopenia. With this new definition, a much larger population of older adults are now at risk of sarcopenia. In the present article, we reviewed the literature for studies which tested the effects of diet or exercise interventions on changes in lean mass and/or functional outcomes in individuals with either sarcopenia and/or frailty and identified 19 clinical trials. There were a few key findings. First, dietary interventions involving protein supplementation improved functional and/or strength outcomes in a few trials; however, other dietary approaches were less effective. Exercise interventions and combined diet and exercise interventions produced consistent improvements in lower body muscle strength but had less consistent effects on walking speed and grip strength. Lifestyle interventions not involving calorie restriction generally did not induce significant changes in body composition. There were a limited number of trials in which participants with sarcopenia were specifically targeted, and thus there is an important need for more research to determine the appropriate types of intervention approaches for the high risk population of sarcopenic older adults.

β-hydroxy-β-methylbutyrate (HMB) is a metabolite derived from leucine and its ketoacid alpha- ketoisocaproate. Leucine has a role in regulating protein synthesis in muscle cells, and HMB seems to be a key active metabolite in such regulation. HMB has been shown to modulate muscle protein degradation by inhibiting the ubiquitin-proteasome proteolytic pathway, to up-regulate protein synthesis via the mTOR pathway, and to stabilize cell membranes via the rate limiting enzyme to cholesterol synthesis HMG- coenzyme A reductase. It can also decrease cell apoptosis, therefore improving cell survival; and increase proliferation and differentiation of muscle stem cell, via the MAPK/ERK and PI3K/Akt pathways. HMB is widely used as an ergogenic supplement by athletes and bodybuilders, usually combined with exercise training, to increase muscle mass and strength. Some studies have explored the role of HMB in chronic diseases associated with muscle wasting (cancer, acquired immunodeficiency syndrome, chronic obstructive pulmonary disease). This review focuses on the role of HMB in the management of sarcopenia (age or disease-related loss of muscle mass and function) in older persons. A small number of studies have shown increases in lean (muscle) mass and some muscle function and physical performance parameters in older people with or without resistance exercise, and preservation of muscle mass during bed rest. However, heterogeneous methodological approaches preclude solid conclusions, and more studies are needed to confirm the role of HMB as a promising agent to treat sarcopenia.

Aging is a multifactorial process characterized by several features including low-grade inflammation, increased oxidative stress and reduced regenerative capacity, which ultimately lead to alteration in morpho-functional properties of skeletal muscle, thus promoting sarcopenia. This condition is characterized by a gradual loss of muscle mass due to an unbalance between protein synthesis and degradation, finally conveying in functional decline and disability. The development of specific therapeutic approaches able to block or reverse this condition may represent an invaluable tool for the promotion of a healthy aging among elderly people. It is well established that changes in the quantity and the quality of dietary proteins, as well as the intake of specific amino acids, are able to counteract some of the physiopathological processes related to the progression of the loss of muscle mass and may have beneficial effects in improving the anabolic response of muscle in the elderly. Taurine is a non-essential amino acid expressed in high concentration in several mammalian tissues and particularly in skeletal muscle where it is involved in the modulation of intracellular calcium concentration and ion channel regulation and where it also acts as an antioxidant and anti-inflammatory factor. The aim of this review is to summarize the pleiotropic effects of taurine on specific muscle targets and to discuss its role in regulating signaling pathways involved in the maintenance of muscle homeostasis. We also highlight the potential use of taurine as a therapeutic molecule for the amelioration of skeletal muscle function and performance severely compromised during aging.

Sarcopenia is the loss of muscle mass and function, affecting up to 70% of patients with advanced liver disease. Liver cirrhosis is characterized by an altered glucose metabolism, lipid oxidation, ketogenesis and protein catabolism, leading to the loss of adipose and muscle tissue. The gastrointestinal dysfunction of cirrhotic patients results in inadequate nutrients intake and is responsible for muscle weakness thus limiting physical exercise and perpetuating the reduction of muscle mass. Recently, alterations of hormonal pathways involved in muscle growth, increased intestinal permeability and changes in the gut microbiota composition have been reported in cirrhotic patients. Interestingly, a role of intestinal bacteria in maintaining muscle health has been hypothesized through the translocation of bacteria and bacterial products into the bloodstream triggering the production of muscle wasting-related cytokines. Sarcopenia is associated with severe outcomes in patients with liver cirrhosis, mostly due to the incidence of disease complications. Furthermore, sarcopenia may represent an important prognostic factor for patients with hepatocellular carcinoma and for those undergoing liver transplantation and can be considered a useful additional tool in the global assessment of patients with advanced liver disease.

Kaiso is a bimodal transcriptional repressor. It binds methylated CpG islands or the sequence- specific consensus in the DNA molecule with the Kaiso zinc-finger domain and recruits repressive protein complexes to these DNA fragments by the interaction of the BTB/POZ domain with the complex of NCoR1 corepressor and histone deacetylase, thereby performing transcription repression. Kaiso is involved in epigenetic regulation of transcription. Moreover, the complex Kaiso and catenin p120ctn modulates the transcription of the Wnt-target genes. The review discusses the role of Kaiso in the central nervous system. Kaiso molecules are abundant in the brain. MRI study did not show any alterations in the whole brain, hippocampus and striatum in Kaiso null mice. However, in Kaiso deficient mice the lateral ventricles were three-fold smaller compared with wild-type control. Kaiso deficiency increased the locomotor and exploratory activities as well as the prepuls inhibition of acoustic startle reflex without any adverse effect on anxiety-related behavior, learning and memory. At the same time, Kaiso deficiency produces a marked antidepressant-like effect. Thus, Kaiso involved in the mechanism of locomotion and depressive-like behavior. Kaiso inhibitors are expected to be promising atypical antidepressant drugs.

Oxygenic photosynthesis provides energy and oxygen for almost all forms of life on earth. This process is based on the energy of photons, which is used to split water and use its electrons to reduce carbon atoms to create organic molecules and thus fix the light energy into a chemical form. Two photosytems working in series are involved in light harvesting and conversion. Both are multi-protein supercomplexes composed of a core complex, where the photochemical reaction takes place, and an antenna system involved in light harvesting. In plants and green algae, the antenna of photosystem II, the photosynthetic complex involved in water splitting, comprises the Light Harvesting Complex II (LHCII) trimers, the most abundant membrane protein on earth. LHCII is composed of highly conserved Lhcb isoforms and all green organisms count a high number of Lhcb. In vascular plants they are classified in three distinct subclasses, Lhcb1, 2 and 3, while in algae and non-vascular plants, these isoforms are less differentiated and called Lhcbm proteins. In this review, we compare LHCII proteins of different organisms, from green algae to angiosperms, and discuss the role of the modifications that occurred through evolution. We highlight the various functions of the different isoforms in photosynthesis, ranging from light harvesting, a common role to all these proteins, to regulations of photosynthesis that rely on specific isoforms.

Spinal cord circuits play a key role in receiving and transmitting somatosensory information from the body and the brain. They also contribute to the timing and coordination of complex patterns of movement. Under disease conditions, such as spinal cord injury and neuropathic pain, spinal cord circuits receive pain signals from peripheral nerves, and are involved in pain development via neurotransmitters and inflammatory mediators released from neurons and glial cells. Despite the importance of spinal cord circuits in sensory and motor functions, many questions remain regarding the relationship between activation of specific cells and behavioral responses. Optogenetics offers the possibility of understanding the complex cellular activity and mechanisms of spinal cord circuits, as well as having therapeutic potential for addressing spinal cord-related disorders. In this review, we discuss recent findings in optogenetic research employing the channelrhodopsin protein to assess the function of specific neurons and glia in spinal cord circuits ex vivo and in vivo. We also explore the possibilities and challenges of employing optogenetics technology in future therapeutic strategies for the treatment of spinal disorders.

Current Protein and Peptide Science, 2014, 15(6): 598-607. Selenium and Selenoproteins: An Overview on Different Biological Systems\ Erika Mangiapane^*, Alessandro Pessione and Enrica Pessione Regrettably authors of the article entitled “Selenium and Selenoproteins: An Overview on Different Biological Systems” declare that due to a oversight at there end, in the original article, there is an error in the reported name of the bacterial strain. The bacterial strain was reported as Lactobacillus reuteri Lb2 (DSM 16143) but it should have been reported as Lactobacillus reuteri Lb26 (DSM 16341). Therefore, any instances of Lb2 (DSM 16143) should be replaced with Lb26 (DSM 16341). The experimental work was conducted on the strain Lactobacillus reuteri Lb26 (DSM 16341), formerly classified as Lactobacillus buchneri Lb26 (DSM 16341). Unfortunately the strain provided was mislabeled as Lactobacillus reuteri Lb2 (DSM 16143), which does not possess any of the specific traits published. The results of the research were unaffected by this labelling issue. The last reference should read: Lamberti, C.; Mangiapane, E.; Pessione, A.; Mazzoli, R.; Giunta, C.; Pessione, E. Proteomic characterization of a seleniummetabolizing probiotic Lactobacillus reuteri Lb26 (DSM 16341) for nutraceutical applications. Proteomics, 2011, 11(11), 2212-2221.