Considering Histone H1 in Age-Related Neurodegeneration

Like all tissues, the brain and nervous system become damaged and dysfunctional with age. While the underlying root causes, the differences between old tissue and young tissue, are well cataloged, how this process unfolds to create specific age-related diseases is still a matter for debate and investigation. If you care about rejuvenation and repair, you don't need to know much more than we do today in order to work on treatments to reverse the differences, but most researchers aim at greater understanding of the process, rather than actually doing something about it. Here researchers look at a small slice of the process of aging and damage in one type of tissue:

In neurodegenerative conditions and following brain trauma it is not understood why neurons die while astrocytes and microglia survive and adopt pro-inflammatory phenotypes. We show here that the damaged adult brain releases diffusible factors that can kill cortical neurons and we have identified histone H1 as a major extracellular candidate that causes neurotoxicity and activation of the innate immune system. Extracellular core histones H2A, H2B, H3 and H4 were not neurotoxic.

Innate immunity in the central nervous system is mediated through microglial cells and we show here for the first time that histone H1 promotes their survival, up-regulates MHC class II antigen expression and is a powerful microglial chemoattractant. We propose that when the central nervous system is degenerating, histone H1 drives a positive feedback loop that drives further degeneration and activation of immune defences which can themselves be damaging. We suggest that histone H1 acts as an antimicrobial peptide and kills neurons through mitochondrial damage and apoptosis.



One of the questions that popped into my head reading this post is - is all non infectious disease age related?

I know you have injuries and certain people have genetic or developmental errors that lead to disease. But is all other non infectious disease caused by the 7 types of damage outlined in the SENS approach?

And if you took a healthy 25 year old and kept repairing this damage at intervals, would they ever get any disease?

It seems like a lot of scientists don't believe disease just has it cause in damage.

Posted by: Jim at March 25th, 2014 10:17 AM

I think that there are a lot of grey areas. For example autoimmune diseases: some of these are not age-related and don't happen to everyone. They are clearly damage in the form of misconfiguration of the immune system when they exist, but it is unclear as to where they fit in the categorization of resulting from environmental versus genetic versus intrinsic damage-generating causes.

Posted by: Reason at March 25th, 2014 2:11 PM
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