Authentic Biochemistry

Pathogens, and abiotic ischaemic damage manifest a constellation of  molecular interactions triggering pattern recognition receptors such as TLR's, with canonical protein binding domains that signal through intracellular cascades such as activating  Ca2+ signaling; eo ipso obtaining potent hyperimmune inflammation,  providing  event ontological foundation and episodic contribution to the aging morbidity in human decline and mortality.

Oncotarget. 2016 Jan 26; 7(4): 4195–4209

Nature Reviews Immunology volume 6, pages644–658(2006)

The removal of damaged neurons and associated synaptic connections with the

simultaneous repair of other neuronal circuits is a mechanism for the sculpting of

the brain network and thus a means by which the highly innervated and connected

prefrontal cortex can receive and respond to neurotransmission from the limbic system.

Reference: Genes (Basel). 2019 Mar; 10(3): 249

Authentic Biochemistry Podcast 27 April 2021

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Cell Reports 2020. V 30, (Issue 5) :1585-1597.e6

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As an hypothetico-deduction,  Dr. Guerra proposes that the Recombination Activating Gene-RAG System is a Potential Candidate in Age Associated Morbidity.

In conjunction with a neutral sphingomyelinase and the subsequent synthesis of diacylglycerol thence promoting activation of a PKC-Zeta, T cell receptor translocation and activation are obtained. 

Prior RAG mediated recombination events in CNS-resident lymphocytes, associated microglia and neurons can lead to recombination event epigenomic ontologies that either promote or curtail a resident hyperimmune response   leading to classical neurodegenerative diseases of the elderly.

References:

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Frontiers in Immunology.2014. 5:100

Front Cell Dev Biol. 2019; 7: 226.

Single-nucleotide polymorphisms and  copy-number variations (CNV’s)  result from genome wide chromosomal abnormalities including large deletions and duplications where the the immune system appears to play a major role in  the accumulation of chromosomal variation.

Aging in humans may be linked to immune-mediated epigenomic epistasis as facilitated by Recombination Activating Gene proteins RAG1 & RAG2 that are canonically linked to V(D)J recombination of the T cell receptor and the B cell immunoglobulins.

Neuroinflammatory mediators play a critical role in the pathophysiology of brain ischemia, exerting either deleterious effects on the progression of tissue damage or beneficial roles during recovery and repair.

These processes occur throughout life and involve the immune system, biochemical pathways, cellular turnover and alteration of gene expression.

Signal transduction cascades allow for genome editing to epigenomic mediation of metabolic event ontologies.

Aging is a process whereby these processes lose specificity and valence, increasingly functioning without appropriate fine control leading to the potential for chronic and more rarely, acute disease states that ultimately result in mortality

An Introduction to the theory of immunoepigenetic tailoring of human instanence.

Dr. Guerra

Authentic Biochemistry Podcast Studios

J Immunol August 1, 2017, 199 (3) 874-884

Ann Rev Cell Dev Biol 2018. 34:111-136

Blood. 2016 Apr 14;127(15):1930-9

J BiolChem. 2017 Aug 25; 292(34): 14292–14307