How might nucleosome integrity affect aging?

Attention conservation notice: Rampant speculation on a paper outside of my field, which is unlikely to be simultaneously both new and interesting.


Using a zebrafish egg extract system, Ziehurt et al have shown that in the absence of nucleosomes (ie, in the “DNA beads” condition, as opposed to the “nucleosome beads” condition), there is no nuclear pore complex (NPC) formation. For example, these DNA extracts lack lamin B3.

Without nuclear pore complexes, cells can’t shuttle necessary proteins and other biomolecules in and out of the nucleus, which is… not good for the nucleus. This could be adaptive for the organism, though, if there is foreign or damaged DNA in the cell.

How does this relate to aging?

1) In general, nucleosome-free regions of the nucleus become more common in aging.

2) A different lamin protein called lamin A, which also acts at the NPC, is mutated in the most severe aging accelerating disease I’m aware of: progeria.

3) So, it’s reasonable to ask: in normal aging, does the loss of nucleosome integrity (because of, perhaps, the hand-wavy “accumulated damage”?) lead to lack of NPC accessibility?

From here, another reasonable question is whether you could find a biomarker of NPC integrity from some sort of high throughput method, such as a DNA sequencing method, that would allow you to measure nucleosome integrity easily across aging and intervention states.

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