Inflammaging: Implications in Sarcopenia

In a world in which life expectancy is increasing, understanding and promoting healthy aging becomes a contemporary demand. In the elderly, a sterile, chronic and low-grade systemic inflammation known as “inflammaging” is linked with many age-associated diseases. Considering sarcopenia as a loss of strength and mass of skeletal muscle related to aging, correlations between these two terms have been proposed. Better knowledge of the immune system players in skeletal muscle would help to elucidate their implications in sarcopenia. Characterizing the activators of damage sensors and the downstream effectors explains the inference with skeletal muscle performance. Sarcopenia has also been linked to chronic diseases such as diabetes, metabolic syndrome and obesity. Implications of inflammatory signals from these diseases negatively affect skeletal muscle. Autophagic mechanisms are closely related with the inflammasome, as autophagy eliminates stress signaling sent by damage organelles, but also acts with an immunomodulatory function affecting immune cells and cytokine release. The use of melatonin, an antioxidant, ROS scavenger and immune and autophagy modulator, or senotherapeutic compounds targeting senescent cells could represent strategies to counteract inflammation. This review aims to present the many factors regulating skeletal muscle inflammaging and their major implications in order to understand the molecular mechanisms involved in sarcopenia

Neurogenic Potential of the 18-kDa Mitochondrial Translocator Protein (TSPO) in Pluripotent P19 Stem Cells

The 18-kDa translocator protein (TSPO) is a key mitochondrial target by which different TSPO ligands exert neuroprotective effects. We assayed the neurogenic potential of TSPO to induce the neuronal differentiation of pluripotent P19 stem cells in vitro. We studied changes in cell morphology, cell proliferation, cell death, the cell cycle, mitochondrial functionality, and the levels of pluripotency and neurogenesis of P19 stem cells treated with the TSPO ligand, PK 11195, in comparison to differentiation induced by retinoid acid (RA) and undifferentiated P19 stem cells. We observed that PK 11195 was able to activate the differentiation of P19 stem cells by promoting the development of embryoid bodies. PK 11195 also induced changes in the cell cycle, decreased cell proliferation, and activated cell death. Mitochondrial metabolism was also enhanced by PK 11195, thus increasing the levels of reactive oxygen species, Ca2+, and ATP as well as the mitochondrial membrane potential. Markers of pluripotency and neurogenesis were also altered during the cell differentiation process, as PK 11195 induced the differentiation of P19 stem cells with a high predisposition toward a neuronal linage, compared to cell differentiation induced by RA. Thus, we suggest a relevant neurogenic potential of TSPO along with broad therapeutic implications

Chronic Treatment with Melatonin Improves Hippocampal Neurogenesis in the Aged Brain and Under Neurodegeneration

Adult hippocampal neurogenesis is altered during aging and under different neuropsychiatric and neurodegenerative diseases. Melatonin shows neurogenic and neuroprotective properties during aging and neuropathological conditions. In this study, we evaluated the effects of chronic treatment with melatonin on different markers of neurodegeneration and hippocampal neurogenesis using immunohistochemistry in the aged and neurodegenerative brains of SAMP8 mice, which is an animal model of accelerated senescence that mimics aging-related Alzheimer’s pathology. Neurodegenerative processes observed in the brains of aged SAMP8 mice at 10 months of age include the presence of damaged neurons, disorganization in the layers of the brain cortex, alterations in neural processes and the length of neuronal prolongations and β-amyloid accumulation in the cortex and hippocampus. This neurodegeneration may be associated with neurogenic responses in the hippocampal dentate gyrus of these mice, since we observed a neurogenic niche of neural stem and progenitor/precursors cells in the hippocampus of SAMP8 mice. However, hippocampal neurogenesis seems to be compromised due to alterations in the cell survival, migration and/or neuronal maturation of neural precursor cells due to the neurodegeneration levels in these mice. Chronic treatment with melatonin for 9 months decreased these neurodegenerative processes and the neurodegeneration-induced neurogenic response. Noticeably, melatonin also induced recovery in the functionality of adult hippocampal neurogenesis in aged SAMP8 mice