The gradual stabilization of the NHOS in hepatocytes correlates with their gradual loss of proliferating potential. Nevertheless, the trend towards stabilization of the NHOS with age is observed in both hepatocytes and post-mitotic neurons despite the fact that neurons already have a very stable NHOS from early post-natal age. This fact strongly suggests that thermodynamic and structural constraints drive the NHOS towards maximum stability in time, as the DNA proceeds to dissipate any residual structural stress independently of any cellular functional need. Moreover, considering that entropy is not a measure of disorder or chaos, but of energy diffusion, dissipation or dispersion in a final state compared to an initial state, a rather even distribution of short DNA loops anchored to the NM satisfies the second law of thermodynamics, since the structural stress along the DNA molecule is more evenly dispersed within the nuclear volume by increasing the number of stable DNA-NM interactions. The increase in the relative proportion of total DNA actually embedded within the NM is Lomitapide Mesylate evidence that DNA-NM interactions augment in time leading to further stabilization of the NHOS. The fact that several genes located on different chromosome territories within the Mepiroxol neuronal nucleus lose in time their original privileged position close to the NM, becoming rather distal to it and so they achieve a distribution relative to the NM typical for most random-sequence DNA tracts, indicates that stabilization of the NHOS occurs as a relentless, physical process above any biological constraint. The Fig. 7 depicts two models that may explain how the genes formerly close to the NM become distal to it as a function of time. In the first model genes become distal to the NM because new MARs located far from the genes become actualized substituting in the NM the previous MARs that were close to the genes. Although something like this may be occurring in the case of hepatocytes it is unlikely for the case of neurons considering that there is no real significant change in the already short average DNA-loop size in neurons as a function of age. However the biochemical data indicate that in P540 neurons a significantly larger fraction of total DNA is embedded in the NM when compared with the corresponding fraction in neurons from earlier ages. This fact is consistent with the second model in Fig. 7 which suggests that the actual length of each established MAR increases as a function of time because more DNA adjacent to the original MAR becomes directly bound to the NM. This results in an overall lesser number of DNA loops with the corresponding displacement of genes to regions relatively distal from the anchoring points to the NM, without significantly changing the average DNA loop size. This model is consistent with our data and with evidence for the existence of rather lengthy MARs, but we cannot directly measure any comparative change in the average MAR length as a function of time since for that purpose we need to destroy the NM in order to liberate the bound MARs, a procedure that leads to unavoidable fragmentation of the formerly bound MARs. Yet, the quantitative changes in the composition of the neuronal NM as a function of age parallel those previously described in aged hepatocytes and may explain how the conditions that allow to increase the direct interactions between DNA and the NM appear in time. Early death is observed in neurons forced to re-enter the cell cycle and neuronal cell cycle activity has been observed early in several diseases that course with neurodegeneration.