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 sphingomyelinase- mediated ceramide lipid raft mobilization and aggregation of membrane receptors plays a crucial role in this pathobiochemical dynamic leading to multiple disease and comorbidity states in the elderly. Classical Papers Examined: Mech Ageing Dev. 2001 Sep 15;122(13):1413-30 Cytometry A. 2006 Mar;69(3):189-91 J Lipid Res. 2007 Jan;48(1):19-29. doi: 10.1194 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Authentic Biochemistry

How Oxysterol LDL associates with macrophage and T lymphocyte infiltration during aging to generate the hyperinflammatory atherosclerotic plaque. DJGPhD. 19.10.21. Authentic Biochemistry.

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 downward reductio to misdirected hyperinflammatory states and the potential for autoimmune disease sequalae. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Aging results in corruption of T lymphocyte differentiation associated with chromatin instability and epithelial to mesenchymal transitions leading to the pre-cancerous state. DJGPhD 16.10.21

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) --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Lymphocyte maturation and the special Innate like Lymphocyte Subclass including Natural Killer and other ILC lineages. DJGPhD.14.10.21. Authentic Biochemistry

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 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Immunosenescence and Inflammaging via thymic Involution and comorbid pathophysiology of obesity and aging present a chronic inflammatory phenotype prone to morbidity. DJGPhD. Oct.04,2021. Authentic BC

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 hemagglutinins, neuraminidases,  bacterial ligands, and cellular ligands related with auto immune diseases, tumour growth, and associated aging morbidity. References Experimental & Molecular Medicine volume 51, Article number: 80 (2019) Cell Death & Disease volume 10, Article number: 315 (2019) Front. Immunol., 28 September 2015 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Natural cytotoxicity receptors (NCR's) within group 3 innate lymphoid cells (ILC3): an association of transcription factors in IBD's and aging. DJGPhD. 03.10.21 Authentic Biochemistry.

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 senescent environment of aging human vasculature, skeletal and cardiac muscle, and the CNS toward pathobiochemical increases in morbidity -presenting disease phenotypes.  References J Biomed Biotechnol. 2011; 2011: 298348. Blood 2009 114:2567-2568;  https://doi.org/10.1182/blood-2009-07-230904 Am J Clin Nutr. 2017 Oct;106(4):1157-1165. doi: 10.3945/ajcn.117.155648.  BIOCHEMISTRY AND CHEMICAL BIOLOGY STRUCTURAL BIOLOGY AND MOLECULAR BIOPHYSICS March 2018  https://elifesciences.org/articles/34394 Sci Signal. 2017 Jan 31; 10(464): eaaf7478. Prostaglandins Leukot Essent Fatty Acids. 2015 Jul;98:49-55. doi: 10.1016/j.plefa.2015.04.007. Int J Biol Sci. 2015; 11(11): 1272–1280 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Omega three fatty acids and PE N-methyl transferase are associated with methylation and acetylation patterning in NK cells via AMPK and stress.DJGPhD. 29 September 2021.

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 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Natural Killer Cell switching via demethylation of Histone 3 LYS may correlate with the human aging phenotypic hyper-inflammatory state. DJGPhD. 28.9.21

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 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

The Genome and the Immunoepigenome interact across a three-way trigonal planar field with the Environment to Obtain the Aging Phenomena. DJGPhD.27.9.21

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 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Natural Killer cells and the epigenomics of gene expression: implications for the aging -senescent human. DJGPhD. 26 .9.21. Authentic Biochemistry

Oxidases, dehydrogenases and oxygenases in the electron transport chain et al. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

REDOX Biochemistry Primer . DJGPhD Authentic Biochemistry . 24.9.21

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! --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Video Lecture Announcement. Please Listen to this audio! Grazie, Dr. Daniel J. Guerra 22.9.21

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. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

The Interferon I role in autoimmune disease and the corruption of mechanisms that lead to age-related morbidity and mortality.DJGPhD. 22.9.21

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. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

The Aging Immune Response and Cellular Differentiation are characterized by Apoptosis vs. Necroptosis Mechanisms. DJGPhD. 20.9.21.Authentic Biochemistry Productions.

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 with a corruption in this fine-tuning that presents in the older sedentary human individual as a simple dysregulation of inflammation that ultimately impairs the ability to ward off otherwise relatively innocuous pathogens while simultaneously punctuating the equilibrium otherwise exerted  to control tissue repair and the potential for cellular proliferation and oncogenesis.  References Nat Immunol. 2018 Jun;19(6):561-570. FEBS Letters 2011 Volume 585, Issue 23, Pages 3829-3835 Scientific Reports 2015 volume 5, Article number: 11789 Ann Allergy Asthma Immunol. 2000 Jul;85(1):9-18  --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Semaphorin works through mToR and thus the abl and AKT kinases in Macrophage reverse switching from lipogenesis to fatty acid oxidation. DJGPhD 18.9.21.

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 in pathological cell degeneration or proliferation, morbidity and death. Dr. Daniel J. Guerra Authentic Biochemistry Production. 18.9.21. Reference Nature Immunology June 2018  19: 561–570 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Macrophage and T lymphocyte Inclusion to the Aging Human Pathobiochemical Phenotype. DJGPhD.Authentic Biochemistry 18.9.21

You have wisely landed upon Authentic Biochemistry, with Dr Daniel J Guerra, where published research and clinical science is interrogated.

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Authentic Biochemistry

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