Caloric restriction in humans reveals immunometabolic regulators of health span.

The extension of life span driven by 40% caloric restriction (CR) in rodents causes trade-offs in growth, reproduction, and immune defense that make it difficult to identify therapeutically relevant CR-mimetic targets. We report that about 14% CR for 2 years in healthy humans improved thymopoiesis and was correlated with mobilization of intrathymic ectopic lipid. CR-induced transcriptional reprogramming in adipose tissue implicated pathways regulating mitochondrial bioenergetics, anti-inflammatory responses, and longevity. Expression of the gene Pla2g7 encoding platelet activating factor acetyl hydrolase (PLA2G7) is inhibited in humans undergoing CR. Deletion of Pla2g7 in mice showed decreased thymic lipoatrophy, protection against age-related inflammation, lowered NLRP3 inflammasome activation, and improved metabolic health. Therefore, the reduction of PLA2G7 may mediate the immunometabolic effects of CR and could potentially be harnessed to lower inflammation and extend the health span.

[Comparative assessment of different approaches for obtaining terminally differentiated muscle cells].

Relevant cell model is essential to study pathogenesis of muscle disorders. However, in the field of muscle research there is no ultimate cell line considered as a standard for studying muscular and neuromuscular diseases. Standard cell line claimed to be well differentiated in muscle lineage, be morphological and physiological similar to mature muscle cells and be easily genetically modified. Therefore, the goal of our study was to pick up available and fruitful cell model of muscle differentiation, that could be further applied for examination of muscular disorder pathogenesis in vitro. We characterized human mesenchymal stem cells (MSC), mature murine muscle fibers and primary murine satellite cells. It has been shown that MSC have very small capacity to myogenic differentiation; moreover, they were able to differentiate only in presence of C2C12 cells. Lentiviral transduction exhibited rather high toxic effect on primary myofibers, and positively transduced cells were not able to response to electrical stimulation, i. e. were functionally inactive. Satellite cells turned out to be the most fruitful cell model since they were easily transduced via lentiviruses and rapidly formed myotubes in differentiation media. Functional analysis of obtained myotubes has confirmed their ability to react to electrical and chemical stimulations; besides, potassium and calcium channels availability has been also demonstrated via patch-clump technique. Taken together, these results imply that satellite cells are the most promising cell line for further experiments aimed at exploring the molecular pathways of muscle pathologies.