necessarily pass throughout and between cells, as well as scale up from the single-cell level to the whole organ level.
Passive mechanical properties of both the intracellular and extracellular environments also contribute to the myriad of 21 mechanical signals that are constantly being transmitted throughout striated muscles. Moreover, mechanical signals that
reach the cell nucleus can also cause changes in the nucleus at the level of the epigenome, affecting chromatin 23 organization and accessibility, mediating a mechano-sensitive regulation of gene expression (Alisafaei et al., 2023).
Thus, the proper regulation of mechanical signals in muscles is likely fundamental to healthy muscle structure and 25 function.
It is well established that changes at the level of chromatin is altered in the context of cardiovascular and 27 skeletomuscular disorders including heart failure and muscular dystrophies (Kim et al., 2016;Rugowska et al., 2021).
The authors compared the structure of the sympathetic neuronal network in healthy muscles and muscles with 39 amyotrophic lateral sclerosis (ALS), a deadly neuromuscular disease. Through their new quantitative imaging approach, 40 they show that sympathetic neurons are compromised in a mouse model of ALS, and that the sympathetic neuron 41 denervation occurs early in disease progression.
In
