Age-Related Alterations at Neuromuscular Junction: Role of Oxidative Stress and Epigenetic Modifications

被引:30
作者
Dobrowolny, Gabriella [1 ]
Barbiera, Alessandra [2 ]
Sica, Gigliola [2 ]
Scicchitano, Bianca Maria [2 ]
机构
[1] Sapienza Univ Rome, Fdn Cenci Bolognetti, Dept Anat Histol Forens Med & Orthopaed DAHFMO, Ist Pasteur Italia,Unit Histol & Med Embryol, I-00161 Rome, Italy
[2] Fdn Policlin Univ A Gemelli IRCCS, Dept Life Sci & Publ Hlth, Histol & Embryol Unit, I-00168 Rome, Italy
关键词
aging; ROS; oxidative stress; ALS; skeletal muscle; nutrition; exercise; AMYOTROPHIC-LATERAL-SCLEROSIS; SKELETAL-MUSCLE ATROPHY; MOTOR-NEURON DEGENERATION; STEM-CELLS; SCHWANN-CELLS; MOUSE MODEL; SATELLITE CELLS; MITOCHONDRIAL DYSFUNCTION; DISEASE PROGRESSION; CALORIC RESTRICTION;
D O I
10.3390/cells10061307
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
With advancing aging, a decline in physical abilities occurs, leading to reduced mobility and loss of independence. Although many factors contribute to the physio-pathological effects of aging, an important event seems to be related to the compromised integrity of the neuromuscular system, which connects the brain and skeletal muscles via motoneurons and the neuromuscular junctions (NMJs). NMJs undergo severe functional, morphological, and molecular alterations during aging and ultimately degenerate. The effect of this decline is an inexorable decrease in skeletal muscle mass and strength, a condition generally known as sarcopenia. Moreover, several studies have highlighted how the age-related alteration of reactive oxygen species (ROS) homeostasis can contribute to changes in the neuromuscular junction morphology and stability, leading to the reduction in fiber number and innervation. Increasing evidence supports the involvement of epigenetic modifications in age-dependent alterations of the NMJ. In particular, DNA methylation, histone modifications, and miRNA-dependent gene expression represent the major epigenetic mechanisms that play a crucial role in NMJ remodeling. It is established that environmental and lifestyle factors, such as physical exercise and nutrition that are susceptible to change during aging, can modulate epigenetic phenomena and attenuate the age-related NMJs changes. This review aims to highlight the recent epigenetic findings related to the NMJ dysregulation during aging and the role of physical activity and nutrition as possible interventions to attenuate or delay the age-related decline in the neuromuscular system.
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