Sarcopenia is defined as an age-associated loss of skeletal muscle function and muscle mass and is common in older adults. Sarcopenia as a disease is currently of interest not only to orthopedists and surgeons but also to internists, endocrinologists, rheumatologists, cardiologists, diabetologists, gynaecologists, geriatricians and paediatricians. In cooperation with the 5th Internal Medicine Clinic, we, as a unit of clinical research, aimed to describe a sarcopenic specific miRNA expression profile for disease diagnostics and classification of the severity of muscle performance deterioration. This study included a total of 80 patients (age 55-86 years) hospitalized at the V. Internal medicine clinic of LFUK and UNB with different severity of muscle performance deterioration. The study participants were evaluated and classified according to short physical performance battery score (SPPB). In this study, we investigated the role of circulating miRNAs in sarcopenia in the elderly. We hypothesized that sarcopenia effects the expression of muscle tissue-specific miRNAs (MyomiRNAs), which could be potentially reflected in the blood plasma miRNA expression profile. The expression of specific circulating miRNAs in patients with different muscle performances was analyzed. Patients’ blood plasma was evaluated for the expression of myomiRNAs: miRNA-29a, miRNA-29b, miRNA-1, miRNA-133a, miRNA-133b, miRNA-206, miRNA-208b and miRNA-499, and the data were correlated with diagnostic indicators of the disease. We showed a specific sarcopenia miRNA profile that could be considered a possible biomarker for the disease. Patients with low muscle performance showed increased miRNA-1, miRNA-29a and miRNA-29b expression and decreased for the miRNA-206, miRNA-133a, miRNA-133b, miRNA-208b and miRNA-499 expression. We show that the severity of muscle performance deterioration in sarcopenia correlates with specific miRNA expression. We also propose the profile of miRNAs expression in blood plasma as a specific biomarker for sarcopenia diagnostics. Future clinical studies will be necessary to eventually naturally have to elucidate the underlined molecular mechanism responsible for specific miRNAs expression in sarcopenia pathology and progression of the disease.

Autologous stem cell therapy is the most promising alternative treatment in patients with chronic ischemic diseases, including ischemic heart disease and critical limb ischemia, which are characterized by poor prognosis related to serious impair of quality of life, high risk of cardiovascular events and mortality rates. However, one of the most serious shortcomings of stem cell transplantation are low survival after transplantation to the site of injury, as large number of stem cells are lost within 24 hours after delivery. Multiple studies suggest that combination of lipid-lowering drugs, statins, and stem cell transplantation might improve therapeutic efficacy in regenerative medicine. Statins are inhibitors of HMG-CoA reductase and belong to recommended therapy in all patients suffering from critical limb ischemia. Statins possess non-lipid effects which involve improvement of endothelial function, decrease of vascular inflammation and oxidative stress, anti-cancer and stem cell modulation capacities. These non-lipid effects are explained by inhibition of mevalonate synthesis via blocking isoprenoid intermediates synthesis, such as farnesylpyrophospate and geranylgeranylpyrophospate and result in modulation of the PI3K/Akt pathway. Moreover, statin-mediated microRNA regulation may contribute to the pleiotropic functions. MicroRNA interplay in gene regulatory network of IGF/Akt pathway may be of special significance for the treatment of critical limb ischemia. We assume further studies are needed for detailed analysis of statin interactions with microRNA at the molecular level and their link to PI3K/Akt and IGF/Akt pathway in stem cells, which are currently the most promising treatment strategy used in chronic ischemic diseases.

Stem cell transplantation represents a unique therapeutic tool in tissue engineering and regenerative medicine. However, it was shown that the post-injection survival of stem cells is poor, warranting a more comprehensive understanding of activated regenerative pathways. Numerous studies indicate that statins improve the therapeutic efficacy of stem cells in regenerative medicine. In the present study, we investigated the effect of the most widely prescribed statin, atorvastatin, on the characteristics and properties of bone-marrow-derived mesenchymal stem cells (BM-MSCs) cultured in vitro. We found that atorvastatin did not decrease the viability of BM-MSCs, nor did it change the expression of MSC cell surface markers. Atorvastatin upregulated the mRNA expression levels of VEGF-A and HGF, whereas the mRNA expression level of IGF-1 was decreased. In addition, the PI3K/AKT signaling pathway was modulated by atorvastatin as indicated by the high mRNA expression levels of PI3K and AKT. Moreover, our data revealed the upregulation of mTOR mRNA levels; however, no change was observed in the BAX and BCL-2 transcripts. We propose that atorvastatin benefits BM-MSC treatment due to its ability to upregulate angiogenesis-related genes expression and transcripts of the PI3K/AKT/mTOR pathway.

Sarcopenia is defined as an age-associated loss of skeletal muscle function and muscle mass and is common in older adults. Sarcopenia as a disease is currently of interest not only to orthopedists and surgeons but also to internists, endocrinologists, rheumatologists, cardiologists, diabetologists, gynaecologists, geriatricians and paediatricians. In cooperation with the 5th Internal Medicine Clinic, we, as a unit of clinical research, aimed to describe a sarcopenic specific miRNA expression profile for disease diagnostics and classification of the severity of muscle performance deterioration. This study included a total of 80 patients (age 55-86 years) hospitalized at the V. Internal medicine clinic of LFUK and UNB with different severity of muscle performance deterioration. The study participants were evaluated and classified according to short physical performance battery score (SPPB). In this study, we investigated the role of circulating miRNAs in sarcopenia in the elderly. We hypothesized that sarcopenia effects the expression of muscle tissue-specific miRNAs (MyomiRNAs), which could be potentially reflected in the blood plasma miRNA expression profile. The expression of specific circulating miRNAs in patients with different muscle performances was analyzed. Patients’ blood plasma was evaluated for the expression of myomiRNAs: miRNA-29a, miRNA-29b, miRNA-1, miRNA-133a, miRNA-133b, miRNA-206, miRNA-208b and miRNA-499, and the data were correlated with diagnostic indicators of the disease. We showed a specific sarcopenia miRNA profile that could be considered a possible biomarker for the disease. Patients with low muscle performance showed increased miRNA-1, miRNA-29a and miRNA-29b expression and decreased for the miRNA-206, miRNA-133a, miRNA-133b, miRNA-208b and miRNA-499 expression. We show that the severity of muscle performance deterioration in sarcopenia correlates with specific miRNA expression. We also propose the profile of miRNAs expression in blood plasma as a specific biomarker for sarcopenia diagnostics. Future clinical studies will be necessary to eventually naturally have to elucidate the underlined molecular mechanism responsible for specific miRNAs expression in sarcopenia pathology and progression of the disease.

Autologous stem cell therapy is the most promising alternative treatment in patients with chronic ischemic diseases, including ischemic heart disease and critical limb ischemia, which are characterized by poor prognosis related to serious impair of quality of life, high risk of cardiovascular events and mortality rates. However, one of the most serious shortcomings of stem cell transplantation are low survival after transplantation to the site of injury, as large number of stem cells are lost within 24 hours after delivery. Multiple studies suggest that combination of lipid-lowering drugs, statins, and stem cell transplantation might improve therapeutic efficacy in regenerative medicine. Statins are inhibitors of HMG-CoA reductase and belong to recommended therapy in all patients suffering from critical limb ischemia. Statins possess non-lipid effects which involve improvement of endothelial function, decrease of vascular inflammation and oxidative stress, anti-cancer and stem cell modulation capacities. These non-lipid effects are explained by inhibition of mevalonate synthesis via blocking isoprenoid intermediates synthesis, such as farnesylpyrophospate and geranylgeranylpyrophospate and result in modulation of the PI3K/Akt pathway. Moreover, statin-mediated microRNA regulation may contribute to the pleiotropic functions. MicroRNA interplay in gene regulatory network of IGF/Akt pathway may be of special significance for the treatment of critical limb ischemia. We assume further studies are needed for detailed analysis of statin interactions with microRNA at the molecular level and their link to PI3K/Akt and IGF/Akt pathway in stem cells, which are currently the most promising treatment strategy used in chronic ischemic diseases.