Authentic Biochemistry

A take-home message from this research may be that the immunosenescent phenotype in the elderly, while associated with an increased rate of infections and a diminished effect of vaccines, and increased cancer susceptibility may be promoted by cancer and /or chemotherapy to cure the cancer. Both cancer and chemotherapy contribute to immune compromise and potential for gene mutations and epigenetic phenomena.

The human body is tempered by cellular fate paradigms that include senescence vs. proliferation during aging. A corruption in the senescnce associated secretory phenotype may be a proximal tareget to reduce aging morbidity but does it not open the door to oncogenesis and the potential for autoimmune disease?

Comput Struct Biotechnol J. 2019; 17: 1151–1161

Nat Med. 2017 Jun; 23(6): 775–781

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Dr Guerra continues his associative pathobiochemical dialectic concerning T lymphocytte differentaition and senescence

The  Th and Tc populations following uptake and processing of an antigen by an APC such as a dendritic cell is presented either to the CD8 population in the context of MHC-I or to the CD4 subpopulation in the context of MHC-II generates a cascading set of cellular lymphoproliferative and differentiative steps initiated under the inductive influence of cytokines that ultimately determine  effector functions.

Papers examined in this episode:

Nat Med. 2017 Jun; 23(6): 775–781

Cancer Genet Cytogenet. 1999 Mar;109(2):108-13.

BMC Cancer volume 20, Article number: 882 (2020)

Dr Guerra swings hard at Treg and naive CD4+/CD8+ lymphocytes in immunosenescence and the potential for infection with aging while accumulating T memory cell lineages confined to antigen./pathogen exposure including vaccine-associated immunizations.

Newe paper disussed today: .Brain Behav Immun 2018 Oct; 73: 546–549.doi: 10.1016/j.bbi.2018.06.019. Epub 2018 Jun 22.

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1. Age -associated Immunosenescence is sometimes treated as synonymous with immune insufficiency, resulting in enhanced  random infections and reduced vaccine immunity, and tumor surveillance

2. Self-reactive immune responses are elevated in the elderly, which is a result of inflammaging, a chronic, low-grade, systemic pro-inflammatory phenotype in the absence of acute infection

3. Immunosenescence and inflammaging are pathophysiological, and can be the immune poise for hyperinflammation and autoimmune disease in the elderly, leading to severe morbidity  and increased mortality.

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Cellular senescence is a physiological process with genetic determinants and external modififiersincluding stress, nutrition and cell fate reprogramming including autophagy and apoptosis.

Human aging is a lifelong teleological process that includes the specifics of cellular senescence plus an underdefined terminus that tracks chronological longevity and occurs in all systems including musculature, solid organs, the PNS and the CNS

Aging is at the organismal level and is inevitable with increasing morbidity with or without definable etiological agency and the end is always death.

 This is in contrast to senescence, which is variable , tissue specific and both plastic and elastic relative to short but stochastic progress that presents with intervals of remission and progression without a necessary uniformity of morbidity or coordinated coincidental death.

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Dr Guerra discusses the Glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR) and its role in stabilizing T Regulatory cell populations relative to T memory cells and T effector Cells in healthy and End-Stage Renal Disease patients of differing chronological age.

This plank is laid down to form the final structural foundations that allow us to examine dialectically, the role(s) of the Immune system on aging and the chronic and auto-immune diseases of the elderly. Published 08 September 2020 by DJGPhD.

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Dr Guerra builds the foundation for transcription factor and epigenetic regulation of Treg cell differentiation in counterbalance to ILC's and T effector lymphocyte populations. Published 01 September 2020.

Dr. Daniel Guerra  recombines the discussions of pharmacotherapeutic inhibition of prenylation in T cell activation and the failure of the NF-Kappa B pathway in estrogen receptor associated  breast cancer and the lymphoproliferative lymphomas and leukemias with aging and neurodegeneration. PUblished 24 August 2020.

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Dr Guerra discusses the induction of transcription factor SREBP in activated T lymphocytes  and the regulation of cellular translocation from the ER to the Golgi to the nucleus for the induction of prenyl and acyl lipogenesis, Published 18 August 2020 by Dr Daniel J. Guerra. 

Review of: Front. Pharmacol., 17 March 2020.  https://doi.org/10.3389/fphar.2020.00265