Biology subjects

Vepkhvadze, T. F.

Publications and source records attributed to Vepkhvadze, T. F..

3 recordsLinked to original sources

bioRxiv2025

Different effects of 3-week disuse on the phenotype and gene expression of the calf and thigh muscles

Disuse, like several other pathological conditions, has specific effects on various skeletal muscles; the mechanisms underlying these responses remain unclear. We aimed to compare the disuse-induced changes in the phenotype and proteome of the calf and thigh muscles, and to assess the extent to which these proteomic changes are regulated at the mRNA and other levels. Twelve healthy young males participated in 3-week bed rest. Disuse resulted in a greater decrease in lean mass, aerobic performance, and changes in the proteome and transcriptome of the calf muscles/m. soleus than the thigh muscles/m. vastus lateralis. A greater decrease in calf muscle mass was associated with a decrease in the expression/deactivation of translation regulators, but not to the expression of the main sarcomeric proteins. At the same time, a significant decrease in aerobic performance of the ankle plantar flexors occurred without changing the expression of oxidative enzymes - a marker of mitochondrial density. That decrease was associated with dysregulation of mitochondrial biogenesis. Most large-scale changes in the transcriptome did not translate into changes in the proteome, indicating post-transcription protein buffering. However, changes in the RNA levels were revealed to play a dominant role in regulating specific proteins, whereas for others, this factor played little or no role. In conclusion, our findings partially explain why calf muscles with a strong postural function are more sensitive to short-term disuse. This provides a foundation for developing targeted approaches to counteract the negative effects of disuse on different muscles.

physiology↗

bioRxiv2024

Multidirectional effect of low-intensity electrical myostimulation on gene expression and phenotype in thigh and calf muscles after one week of disuse

PurposeThis study investigated the effects of a one-week disuse, both with and without low-intensity neuromuscular electrical stimulation - a safe (non-traumatic) approach to prevent the loss of muscle mass, on the functional capacities and gene expression in thigh and calf muscles. MethodsThis study assessed the efficiency of low-intensity ([~]10% of maximal voluntary contraction) electrical stimulation in preventing the negative effects of 7-day disuse (dry immersion without and with daily stimulation) on the strength and aerobic performance of the ankle plantar flexors and knee extensors, mitochondrial function in permeabilized muscle fibers, and the proteomic (quantitative mass spectrometry-based analysis) and transcriptomic (RNA-sequencing) profiles of the soleus muscle and vastus lateralis muscle. ResultsApplication of electrical stimulation during dry immersion prevented a decrease in the maximal strength and a slight reduction in aerobic performance of the knee extensors, as well as a decrease in maximal (intrinsic) ADP-stimulated mitochondrial respiration and changes in the expression of genes encoding mitochondrial, extracellular matrix, and membrane proteins in the vastus lateralis muscle. In contrast, for the ankle plantar flexors/soleus muscle, electrical stimulation had a positive effect only on maximal mitochondrial respiration, but slightly accelerated the decline in the maximal strength and muscle fiber cross-sectional area, which appears to be related to the activation of inflammatory genes. ConclusionThe data obtained open up broad prospects for the use of low-intensity electrical stimulation to prevent the negative effects of disuse for "mixed" muscles, meanwhile, the optimization of the stimulation protocol is required for "slow" muscles. Practitioner PointsO_LILow-intensity electrical myostimulation is often used as an alternative to exercise and high-intensity electrical stimulation to prevent the loss of muscle mass and function in patients with severe chronic diseases and in spaceflight. However, its effect on muscles with different functional capacities remains uncertain. C_LIO_LIOne week of disuse (dry immersion) lead to a comparable decrease in the maximal strength and (intrinsic) mitochondrial respiration in both the ankle plantar flexors/soleus muscle and the knee extensors/vastus lateralis muscle. Meanwhile changes in gene expression (transcriptome) were three times more pronounced in the soleus muscle than in the vastus lateralis muscle. C_LIO_LIApplication of electrical stimulation during disuse prevented most of the negative effects of disuse in the knee extensors/vastus lateralis muscle, but accelerated the decline in the maximal strength/muscle fiber cross-sectional area in the ankle plantar flexors/soleus muscle, which may be related to the activation of genes regulating the inflammatory response. C_LI

physiology↗

bioRxiv2023

Age-related changes in human skeletal muscle transcriptome and proteome are moreaffected by chronic inflammation and physical inactivity than primary aging

Evaluation of the influence of primary and secondary aging on the manifestation of molecular and cellular hallmarks of aging is a challenging and currently unresolved issue. Our study represents the first demonstration of the distinct role of primary aging and chronic inflammation/physical inactivity - the most important drivers of secondary aging, in the regulation of transcriptomic and proteomic profiles in human skeletal muscle. To achieve this purpose, young healthy people (n=15), young (n=8) and older (n=37) patients with knee/hip osteoarthritis, a model to study the effect of long-term inactivity and chronic inflammation on the vastus lateralis muscle, were included in the study. It was revealed that widespread and substantial age-related changes in gene expression in older patients relative to young healthy people ([~]4,000 genes regulating mitochondrial function, proteostasis, cell membrane, secretory and immune response) were related to the long-term physical inactivity and chronic inflammation rather than primary aging. Primary aging contributed mainly to the regulation of genes ([~]200) encoding nuclear proteins (regulators of DNA repair, RNA processing, and transcription), mitochondrial proteins (genes encoding respiratory enzymes, mitochondrial complex assembly factors, regulators of cristae formation and mitochondrial reactive oxygen species production), as well as regulators of proteostasis. It was found that proteins associated with aging were regulated mainly at the post-transcriptional level. The set of putative primary aging genes and their potential transcriptional regulators can be used as a resource for further targeted studies investigating the role of individual genes and related transcription factors in the emergence of a senescent cell phenotype.

physiology↗