The role of physical activity in counteracting age-related sarcopenia and cancer cachexia: A brief literature review

Muscle tissue plays several important health functions . In addition to the important mechanical functions, it represents the biggest reserve of body proteins and it is also able to produce several myokines that are able to induce important beneficial effects, through the interaction with different organs. The loss of muscle mass has a tremendous impact on health and it is not surprising that a great interest has raised on two degenerative, irreversible and unstoppable conditions known as sarcopenia and cachexia. Sarcopenia, the age-related loss of muscle mass, is not a disease or a syndrome, it is not even a medical sign sometimes. Indeed, a general consensus among scientists does not exist regarding the definition and the identification criteria of this condition. On the other hand, cachexia is a wasting syndrome characterized by an uncontrolled and unstoppable loss of muscle mass, associated with fatigue and weakness. It is often associated with a disease like cancer, AIDS, Chronic Obstructive Pulmonary Disease (COPD), multiple sclerosis, tuberculosis etc. Given the complexity of these muscle conditions and considering that during aging and cancer there is an increased risk of comorbidities, regular physical activity might be a crucial point to be carefully evaluated on a single patient basis. The aim of this review is to highlight the impact on society and the etiology of sarcopenia and cancer cachexia, with particular regard to the role played by physical activity in preventing and counteracting these muscle-wasting conditions, focusing attention also on the limitation factors that must be considered during the prescription of physical activity to sarcopenic and cachectic patients

In vitro susceptibility of thioredoxins and glutathione to redox modification and aging-related changes in skeletal muscle

AbstractThioredoxins (Trx's) regulate redox signaling and are localized to various cellular compartments. Specific redox-regulated pathways for adaptation of skeletal muscle to contractions are attenuated during aging, but little is known about the roles of Trx's in regulating these pathways. This study investigated the susceptibility of Trx1 and Trx2 in skeletal muscle to oxidation and reduction in vitro and the effects of aging and contractions on Trx1, Trx2, and thioredoxin reductase (TrxR) 1 and 2 contents and nuclear and cytosolic Trx1 and mitochondrial Trx2 redox potentials in vivo. The proportions of cytosolic and nuclear Trx1 and mitochondrial Trx2 in the oxidized or reduced forms were analyzed using redox Western blotting. In myotubes, the mean redox potentials were nuclear Trx1, −251mV; cytosolic Trx1, −242mV; mitochondrial Trx2, −346mV, data supporting the occurrence of differing redox potentials between cell compartments. Exogenous treatment of myoblasts and myotubes with hydrogen peroxide or dithiothreitol modified glutathione redox status and nuclear and cytosolic Trx1, but mitochondrial Trx2 was unchanged. Tibialis anterior muscles from young and old mice were exposed to isometric muscle contractions in vivo. Aging increased muscle contents of Trx1, Trx2, and TrxR2, but neither aging nor endogenous ROS generated during contractions modified Trx redox potentials, although oxidation of glutathione and other thiols occurred. We conclude that glutathione redox couples in skeletal muscle are more susceptible to oxidation than Trx and that Trx proteins are upregulated during aging, but do not appear to modulate redox-regulated adaptations to contractions that fail during aging

MiR-23-TrxR1 as a novel molecular axis in skeletal muscle differentiation

Thioredoxin reductase 1 (TrxR1) is a selenocysteine-containing protein involved in cellular redox homeostasis which is downregulated in skeletal muscle differentiation. Here we show that TrxR1 decrease occurring during myogenesis is functionally involved in the coordination of this cellular process. Indeed, TrxR1 depletion reduces myoblasts growth by inducing an early myogenesis -related gene expression pattern which includes myogenin and Myf5 up-regulation and Cyclin D1 decrease. On the contrary, the overexpression of TrxR1 during differentiation delays myogenic process, by negatively affecting the expression of Myogenin and MyHC. Moreover, we found that miR-23a and miR-23b - whose expression was increased in the early stage of C2C12 differentiation - are involved in the regulation of TrxR1 expression through their direct binding to the 3′ UTR of TrxR1 mRNA. Interestingly, the forced inhibition of miR-23a and miR-23b during C2C12 differentiation partially rescues TrxR1 levels and delays the expression of myogenic markers, suggesting the involvement of miR-23 in myogenesis via TrxR1 repression. Taken together, our results depict for the first time a novel molecular axis, which functionally acts in skeletal muscle differentiation through the modulation of TrxR1 by miR-23

Explosive type of moderate-resistance training induces functional, cardiovascular, and molecular adaptations in the elderly

Current recommendations aimed at reducing neuromuscular and functional loss in aged muscle have identified muscle power as a key target for intervention trials, although little is known about the biological and cardiovascular systemic response in the elderly. This study investigated the effects of 12 weeks of low-frequency, moderate-intensity, explosive-type resistance training (EMRT) on muscle strength and powerin oldcommunity-dwellingpeople(70–75years), monitoring functional performance linked to daily liv- ing activities (ADL) and cardiovascular response, as well as biomarkers of muscle damage, cardiovascular risk, and cellular stress response. The present study provides the first evidence that EMRT was highly effective in achieving a significant enhancement in muscular strength and power as well as in functional performance without causing any detrimental modification in cardiovascular, inflammatory, and damage parameters. Moreover, trained elderly subjects showed an adaptive response at both systemic and cellular levels by modulation of antioxidant and stress-induced markers such as myeloperoxidase (MPO), heat shock protein 70 (Hsp70) and 27 (Hsp27), and thioredoxin reductase 1 (TrxR1)

An animal and cellular study on αB-crystallin activation in cardiac muscle by acute exercise

Alpha-B-Crystallin (CRYAB), a Small Heat Shock Protein sensitive to oxidative stress, is expressed in many tissues and implicated in various biological processes. In cardiac muscle, CRYAB exerts a cardio protective role in ischemia-induced damage preventing apoptosis and necrosis. In the present study we used forty young (7-weeks old) healthy male mice (BALB/c AnNHsd), which after 1 week of acclimatization to the new housing environment, runned 2 days per 10 minutes. The TR mice ran for 60 min at a speed of 5.5 m/min. Mice were sacrificed immediately after, 15 and 120 minutes after the end of the acute bout of endurance exercise (TR-0’, TR-15’ and TR-120’, respectively). We prepared samples from the heart and from the group of posterior muscles study αB-crystallin’ response at different time of recovery from an acute aerobic exercise (1 hour), correlating its modulation with oxidative stress level. We found that a single bout exercise lead to a specific short-term increase of phospho-αB-crystallin level (pCRYAB), without changes of its total expression. Further, the level of 4-hydroxynonenal, a marker of lipidic peroxidation, has shown a similar trend of pCRYAB enhancement. This may indicate that CRYAB in cardiac muscle is activated and it has a putative role in oxidative stress during exercise. These results are supported by our previous data obtained in mouse skeletal tissues (i.e. gastrocnemius, soleus) and in H₂O₂-treated C2C12 myotubes. In particular we observed not only a fiber-dependent response of pCRYAB, but also its translocation into myofibrillar compartment. Experiments are in progress to further investigate on CRYAB role during exercise and its interactions with cytoskeletal structures

Morpho-Functional Evaluation of Full-Thickness Macular Holes by the Integration of Optical Coherence Tomography Angiography and Microperimetry

(1) Objective: To use optical coherence tomography angiography (OCTA) and microperimetry (MP) to evaluate the correlation between retinal structure and function in patients with idiopathic, full-thickness macular holes (FTMHs) (2) Methods: This prospective, observational study included 11 eyes of 10 patients with FTMHs evaluated before surgery using OCTA and MP. MP sensitivity maps were superimposed and registered on slabs corresponding to superficial capillary plexus (SCP) and deep capillary plexus (DCP) on OCTA, and on the outer plexiform layer (OPL) and the Henle fiber layer (HFL) complex in en face OCT. On these maps, mean retinal sensitivity was calculated at 2 degrees and 4 degrees, all centered on the FTMH. Cystic cavity extension was assessed on the slab corresponding to the OPL + HFL complex in en face OCT and DCP in OCTA using the Image J software (Version 1.49v; National Institutes of Health, Bethesda, MD, USA); (3) Results: Absolute scotomas were observed corresponding to the FTMH. Additionally, rings of relative scotoma in the perilesional area were detected and correlated to the cystic spaces on en face OCT and OCTA. There was a significant correlation between reduced retinal sensitivity at 2 degrees and 4 degrees diameters around the FTMH and the extension of cystic areas (p < 0.01). There was a significant correlation between the extension of cystic cavities and BCVA (p < 0.01). (4) Conclusions: Morpho-functional analysis of FTMH using OCTA and MP, and the correlation between vascular abnormalities and impaired retinal sensitivity, may provide new, useful information. This integrated evaluation of FTMH may be useful to determine the function-structure correlation before and after vitreoretinal surgery, in order to gain a better understanding of the functional consequences induced by the morphological alterations, assessing outcomes in a more objective way, and potentially adding new surgical prognostic factors

Association analysis of ACE and ACTN3 in Elite Caucasian and East Asian Swimmers

PURPOSE: Polymorphic variation in the angiotensin-converting enzyme (ACE) and alpha-actinin-3 (ACTN3) genes has been reported to be associated with endurance and/or power-related human performance. Our aim was to investigate whether polymorphisms in ACE and ACTN3 are associated with elite swimmer status in Caucasian and East Asian populations. METHODS: ACE I/D and ACTN3 R577X genotyping was carried out for 200 elite Caucasian swimmers from European, Commonwealth, Russian and American cohorts (short and middle distance, SMD ≤ 400 m, n = 130; long distance, LD greater than 400 m, n = 70) and 326 elite Japanese and Taiwanese swimmers (short distance, SD ≤ 100 m, n = 166; middle distance, MD: 200 - 400 m, n = 160). Genetic associations were evaluated by logistic regression and other tests accommodating multiple testing adjustment. RESULTS: ACE I/D was associated with swimmer status in Caucasians, with the D-allele being overrepresented in SMD swimmers under both additive and I-allele dominant models (permutation test p = 0.003 and p = 0.0005, respectively). ACE I/D was also associated with swimmer status in East Asians. In this group, however, the I-allele was overrepresented in the SD swimmer group (permutation test p = 0.041 and p = 0.0098 under the additive and the D-allele-dominant models, respectively). ACTN3 R577X was not significantly associated with swimmer status in either Caucasians or East Asians. CONCLUSIONS: ACE I/D associations were observed in these elite swimmer cohorts, with different risk alleles responsible for the associations in swimmers of different ethnicities. The functional ACTN3 R577X polymorphism did not show any significant association with elite swimmer status, despite numerous previous reports of associations with 'power/sprint' performance in other sports.Additional co-authors: Jason Gulbin, Viktor A. Rogozkin, Ildus I. Ahmetov, Nan Yang, Kathryn N. North, Saraslanidis Ploutarhos, Hugh E. Montgomery, Mark E.S. Bailey, and Yannis P. Pitsiladi

Alpha B-Crystallin in Muscle Disease Prevention: The Role of Physical Activity

HSPB5 or alpha B-crystallin (CRYAB), originally identified as lens protein, is one of the most widespread and represented of the human small heat shock proteins (sHSPs). It is greatly expressed in tissue with high rates of oxidative metabolism, such as skeletal and cardiac muscles, where HSPB5 dysfunction is associated with a plethora of human diseases. Since HSPB5 has a major role in protecting muscle tissues from the alterations of protein stability (i.e., microfilaments, microtubules, and intermediate filament components), it is not surprising that this sHSP is specifically modulated by exercise. Considering the robust content and the protective function of HSPB5 in striated muscle tissues, as well as its specific response to muscle contraction, it is then realistic to predict a specific role for exercise-induced modulation of HSPB5 in the prevention of muscle diseases caused by protein misfolding. After offering an overview of the current knowledge on HSPB5 structure and function in muscle, this review aims to introduce the reader to the capacity that different exercise modalities have to induce and/or activate HSPB5 to levels sufficient to confer protection, with the potential to prevent or delay skeletal and cardiac muscle disorders

Corneal crosslinking: riboflavin concentration in corneal stroma exposed with and without epithelium.

PURPOSE: To evaluate intrastromal concentrations of riboflavin with and without epithelium to ensure the efficacy and safety of corneal crosslinking (CXL) by the standard and transepithelial procedures. SETTING: Department of Ophthalmology and Department of Pharmacology G. Segre, Siena University, Siena, Italy. METHODS: This study comprised keratoconic patients enrolled for penetrating keratoplasty (PKP) and warm-stored sclerocorneal rings unsuitable for transplantation. Half the PKP specimens were debrided, and half were left with the epithelium in situ. One of the latter and 1 debrided sample were not exposed to riboflavin (controls). Samples in both groups were soaked with 0.1% riboflavin-dextran 20% solution instilled every 2 minutes for 5, 15, and 30 minutes. Riboflavin concentrations were determined by high-performance liquid chromatography (HPLC). RESULTS: The study evaluated 14 PKP specimens and 16 sclerocorneal rings. Control samples did not show a riboflavin emission peak. In exposed samples with epithelium, the mean riboflavin concentration was 91.88 ng/g after 5 minutes of exposure, 95.60 ng/g after 15 minutes, and 94.92 ng/g after 30 minutes. In the debrided samples, the mean riboflavin concentration was 14.42 microg/g, 20.92 microg/g, and 24.06 microg/g, respectively. No differences were seen between the in vivo samples and the ex vivo samples. CONCLUSIONS: The HPLC quantitative study showed that stromal concentrations of riboflavin increased with exposure time only if the epithelium was removed. A theoretically safe and effective riboflavin concentration of 15 microg/g was obtained for ultraviolet A-induced CXL only after the epithelium was removed and after at least 10 minutes of riboflavin application every 2 minutes