Aging Muscle Sample Clauses

Aging Muscle. 6 1.2 Nucleocytoplasmic transport 8 1.2.1 Nuclear envelope 9 1.2.2 Nuclear pore complex 11 1.2.3 Nuclear transport receptors 17 1.3 Multinucleated cells 20 1.3.1 Multinucleated single-celled organisms 21 1.3.2 Multinucleated cells in multicellular organisms 23 1.4 Summary 30

Aging Muscle. Starting around age 30 in humans, muscle mass and strength begin an overall decline, and the rate of decline increases rapidly after age 60 (Metter, Conwit et al. 1997, Bassey 1998, Frontera, Xxxxxx et al. 2000). The loss of muscle mass and strength results from hypoplasia (loss of muscle cells) and atrophy (reduction in the size of the remaining muscle cells). In addition, motor units undergo a switch from fast motor units to slow motor units (Xxxxxxxx, XxXxxxx et al. 1973), increasing delays in reaction time and increasing the risk of loss of balance and falls. Decreased muscle function increases morbidity and decreases quality of life for the elderly. Reduced muscle strength is associated with reduced mobility (Xxxxx, Rejeski et al. 2011, Xxxxxx, Xxxxxx et al. 2013) and greater risk of falls (Cesari, Kritchevsky et al. 2005, Xxxxx, Xxxxxxxx et al. 2012) and disability (Xxxxxx, Xxxxxxxx et al. 2006, Xue, Xxxxxxx et al. 2011). The functional and physiological changes in aging muscle are accompanied by changes in the transcriptome and epigenome. mRNA levels are altered in aging: transcripts related to metabolism are depleted in older muscle, while transcripts related to inflammation and damage response are enriched (Xxxx, Xxxx et al. 2006, Xxx, Park et al. 2014, Su, Ekman et al. 2015). These changes reflect functional changes like myofiber type switching. xxXXX expression and DNA methylation also change with age. Levels of miRNAs regulating transcripts involved in transcription and differentiation are altered (Xxx, Park et al. 2014). Aging is also correlated with global DNA hypermethylation (Xxxxxxxx, Xxxxxxx et al. 2014). While there are established connections between altered gene expression and the loss of muscle mass and function, the molecular mechanisms driving a shift in gene expression remain elusive. The changes in transcript levels with age are also accompanied by proteomic changes in aging muscle. Approximately 10% of proteins in rat skeletal muscle change significantly with age (Xxxxxxxxx, Xxxxx et al. 2009). Most age-associated changes in human and rodent skeletal muscle are detected in contractile and metabolic proteins (Baraibar, Gueugneau et al. 2013, Holland, Xxxxxxx et al. 2014). Sarcomeric and metabolic proteins are orders of magnitude more abundant than other proteins in the tissue, so these proteins dominate any proteomic analysis to the exclusion of low abundance proteins. In mouse and human samples ~50% of proteins identified and ~80...