Authentic Biochemistry

1.Biochemistry and Cell Biology of Ageing: Part II Clinical Science. 2019. pp 21-43. The Immune System and Its Dysregulation with Aging.  Ludmila Müller, Svetlana Di Benedetto, and Graham Pawelec. Springer Publishers. 2. Aging (Albany NY). 2019 Apr 30; 11(8): 2343–2351. 3. Immun Ageing. 2020; 17: 2

References Front. Immunol., 29 June 2012  J Immunol 2016;197:3762-3770 Front. Immunol., 03 February 2020

The Src-family kinase Lck regulates T-cell development, activation, proliferation, and immune synapse dynamics. These are the initiation phases of TCR  signaling. Upon antigen presentation via the APC- TCR immune synapse, Lck phosphorylates tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAMs) of the TCR-associated CD3 membrane protein domains.  Phosphoryla...

Dr Guerra carries out the synthesis of multiple pathobiochemical events into an architechtonic of the aging human co-morbidity resulting in a sickness unto death. Authentic Biochemistry Production 22 October 2021 References Cardiovasc Diabetol. 2020; 19: 33. Cytometry A. 2006 Mar;69(3):189-91 Nat Rev Dis Primers. 2019 Mar 7;5(1):16 J Lipid Res. 2007 Jan;48(1):19-29. doi: 10.1194 Mech Ageing Dev. 2...

That there are senescence-associated  decreases in the JAK-STAT signaling transduction cascade has been observed in human lymphocyte lineages. This phenomena, as  associated with a decreased JAK- tyrosine phosphorylation of STAT5, is linked to plasma membrane cholesterol content. Therefore, plasma membrane cholesterol content is involved in T cells modulation and proliferation. Acid sphi...

Chromatin instability leads to alterations in gene expression that re-directs cellular senescence by corruption of chemokine and cytokine signalling resulting in epithelial to mesenchymal transitions and the potential for metastatic cancer in the elderly . As lymphocyte lineage's age these underlying pathobiochemical events are potentiated by hypo and hyper immune responses thus generating a downw...

Front Cell Dev Biol . 2019; 7: 226 Advances in Immunology. 2011 v.109.Pp125 Cell Reports 10, 2043–2054, March 31, 2015 Experimental & Molecular Medicine volume 51, pages1–15 (2019)

Dr. Guerra details the aging immune phenotype at the transcriptional and metabolic level. References Immun Ageing. 2020; 17: 2. Experimental & Molecular Medicine volume 51, Article number: 80 (2019) Nat Immunol. 2011 Nov 6; 12(12): 10 Cell 146, 772–784, September 2, 2011 Nat Immunol. 2014 Aug; 15(8): 767–776. Cell Reports Volume 17, Issue 11, 13 December 2016, Pages 2827-2836

ILC3 can contribute to the progression and aggravation of IBD's while both IL-22 and IL-17, along with IFN-γ, are overexpressed by the dysregulation of NCR− ILC3 or NCR+ ILC3 function NCR (natural cytotoxicity receptors), are  type 1 transmembrane proteins of the immunoglobulin superfamily. Upon stimulation, NCR's mediate NK killing and release of IFNγ. They bind viral ligands such as hemaggl...

Omega-Three VLCPUFA's as asymmetrically distributed in membrane glycerolphospholipids mediate vesiculation and permeability of endothelia to circulating lymphocytes and leukocytes thus coupling folic acid, Vitamin B12 and epigenetic modification of chromatin to ultimately link bioenergetics with cytotoxicity and inflammation. This regulated system involves the neuroimmunoepigenome and the senescen...

Pro-inflammatory gene transcription is tanked when demethylation is inhibited but cytotoxicity of  virally infected or cancer cells by NK’s (where demethylation is inhibited) remains intact. References J. Biol. Chem. 2018;293:2422-2437 J. of Biol. Chem. 2016. 291, 23756-23768

Dr. Guerra discusses some of the complexity of both the epigenetic mechanisms and cellular responses associated with immunomodulatory failure  in the aging human. References  Anal Cell Pathol (Amst). 2018; 2018: 787.1814. Daniel J. Guerra. 2018. DOI: 10.5772/intechopen.82176  https://www.intechopen.com/chapters/64596

Dr. Guerra continues a dialectical accounting of the biochemical and cellular events leading to the terminal outcome of aging. Topic today is the reintroduction of Natural Killer Cells and the epigenetic mechanisms that orchestrate unique gene expression.  References Anal Cell Pathol (Amst). 2018; 2018: 787.1814. The Journal of Biological Chemistry2018. 293: 2422-2437

Oxidases, dehydrogenases and oxygenases in the electron transport chain et al.

This is the link to my new (second in the series) of synoptic Human Aging YouTube lectures. https://youtu.be/IckyMGw8Ffs Please subscribe to both my podcast and YouTube channels! And please contribute! It is the First day of Autumn. Enjoy!

Interferons are innate immune agents of inflammation and recovery. Mutations or epigenetic modifications associated with advanced aging may corrupt interferon pathway  fidelity involving mitophagy leading to autoimmune disease and morbidity later in life. References Nat Immunol. 2021 Mar; 22(3): 312–321 J Neuroinflammation. 2019; 16: 236.

A general audio lecture involving a molecular interactome mediating  the  innate immune response and the control over T and B lymphocyte memory cells resulting in long term potentiation of autoimmune disease during aging.

I discuss the complex  but potent interactions of TLR signaling with plasma membrane protein complexes including  semaphorin cytoplasmic kinase interactions leading to PPAR gamma transcription that fires off CD36 and beta oxidation gene transcription to switch M1 to M2 macrophage polarity thus feedback regulating the pro-inflammatory glycolytic mToRC system dynamics. Aging is associated...

Macrophage polarization and differentiation works in conjunction with CD4+ T lymphocyte differentiation into Th1 and Th2 subclasses and both NK and B cell activities. The aging human loses feedback control over the pro-inflammatory and anti-inflammatory pathways from these classical cellular differentiations contributing to hyperinflammation and/or hypoinflammatory responses ultimately resulting i...

https://youtu.be/4sW-BNVhzrs

Dr. Guerra introduces a primer on membrane biochemistry in preparation for a florid analysis of autophagy and the various forms of programmed cell death linked to the aging human. References Cell Discovery volume 7, Article number: 4 (2021)

Non coding RNA may regulate melanogenesis and in combination with plasma cell producing IgG the nutritional regulation of satiety. Aging results in alterations of this complex system thus resulting in localized melanogenesis and a corruption of the HPA axis. References: Aging (Albany NY). 2021 Jan 31; 13(2): 2700–2726. Stem Cells Int. 2020; 2020: 1047896. First Published online 2020 Jul 8 PNAS. 20...

Components of metabolic sequence toward gluconeogenesis in the human liver.

Dr. Guerra details the glucagon and epinephrine mediated control through Stimulatory G-protein couple adenylate cyclase activating PKA over Hepatic Glycolysis and Gluconeogenesis. 

Utilization of a protein cysteine SH derived thioester intermediate alters the free energy hurdle for the synthesis of 1,3 bis PGA thus allowing for glycolytic ATP and NADH synthesis.