Authentic Biochemistry

Dr. Guerra offers a deep investigation into the roles of sirtuins in homeostasis , aging and disease as linked to NAD+ metabolism via ecto enzymatic CD38 and intracellular forms of this NAD+ metabolizing enzyme that is associated with T lymphocyte bioenergetics, activation and regulation as embedded within the inflammatory response, disease and aging. Published in Authentic Biochemistry Podcast series on Aging and the immune system. 14 October 2020 Papers mentioned in today's lecture : Hogan, et al. Front. Immunol., 31 May 2019 | Cells 2020, 9(1), 228 Camacho-Pereira et al., 2016, Cell Metabolism 23, 1127–1139 Sci. Signal. 10, eaal3024 (2017) 17 October 2017 November 2011 Pharmacological reviews 64(1):166-87 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

Sirtuins are protein deacetylases with multiple isoforms active in the nucleus, cytosol and mitochondria all serving unique functions and requiring NAD+. These sirtuins function to condense chromatin and yet  protein abundance has less to do with potency than does the availability of NAD+ which can be synthesized from multiple routes. Furthermore, SIRT1 has been associated with  antagonizing age-related decreases in the amplitudes of the SCN output obtaining age-linked differentiating  phases of increases and decreases observed within a circadian cycle.. References: Int J Mol Sci. 2019 Mar; 20(5): 1223. PLOS One November 25, 2014 https://doi.org/10.1371/journal.pone.0113939 Circ Res. 2018 Sep 14; 123(7): 868–885 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

It is proposed that the endocrine hormone melatonin may regulate after its synthesis and secretion from  the pineal gland, the deacetylase acivity of Sirtuin1 to diminish the SASP repertoire of aging and may be linked to common morbidity of pathophysiology linked to COPD and generic Respiratory Distress Syndrome  (RDS)presentation. Papers of Record in this episode Int J Mol Sci. 2019 Mar; 20(5): 1223. Int. J. Mol. Sci. 2014, 15, 16848-16884 International Immunopharmacology Volume 62, September 2018, Pages 23-28 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

Dr.  Guerra temporally organizes the lecture series toward the dialectical event by mindfully schematizing the SASP , the triad of DNA Damage Repair (DDR)responses, transcriptionally activated  pro-inflammatory cytokine mediated  inflammation, and the pineal-endocrine hormone melatonin circadian clock manifestations  in the biochemistry and physiology of the aging human. Please SUBSCRIBE! and when you can PLEASE DONATE to your favorite authentic biochemist so he can continue to provide with august research science interrogation and analysis.  --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

Lipids, proteins carbohydrates  and nucleotides-may function within  an inflammatory and secretory modality. Thus, the SASP-Senescence-Associated Secretory Phenotype might deliver apoptosis, necroptosis, autophagy, oncogenesis or an extended  senescence sequalae. An Authentic Biochemistry audio lecture podcast by  Dr. Daniel J. Guerra. 04 October 2020. Please SUBSCRIBE , check out my video lectures ( https://www.youtube.com/channel/UCcEoA2N9WSlNvDk1BtuznfQ?view_as=subscriber) and donate! https://podbay.fm/p/authentic-biochemistry Grazie! Dr. Guerra Nature Reviews | Cancer Reviews 19 | AUGUST 2019 :pp. 439 Nature Communications Vol. 9, Article number: 1228 (2018) doi:10.1038/s41467-018-03566-5 Front. Genet., 12 March 2015 https://doi.org/10.3389/fgene.2015.00094 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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. Please subscribe to Authentic Biochemistry podcast and donate to its continued longevity!  --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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 Support your biochemistry podcast! Be "Authentic" and send donations now!  Dr Guerra thanks you ! --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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

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. PLeasse donate to Authentic Biochemistry! I need your financial support in these trying times.  --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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. Please subscribe and support our podcast with funding! --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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. PLEASE CONTRIBUTE TO my PODCAST TODAY! --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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. Please subscribe to Authentic Biochemistry and give us a % star review and please donate directly to the podcast or join our Patreon page https://anchor.fm/dr-daniel-j-guerra --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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

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. Please join our Patreon and contribute to Authentic Biochemistry today! --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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

In this segment I discuss the phenomenon of DNA and genomic instability and the DNA repair systems implemented  as mechanisms to drive cellular longevity . 06 August 2020 . --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

Programmed Cell Death is a classical cell fate that occurs during embryonic development, tissue repair and both leucocyte and lymphocyte turnover. Various subforms of apoptosis ( classical, necroptosis and ferroptosis) are also involved during infection, genotoxicity, oncogenesis and aging. Published By Dr Guerra 05 August 2020. Subscribe to the podcast! Contribute on Patreon!  --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

Dr Guerra discusses the cancer marker gene mKI67 and its turnover linked to predisposition to euchromatin formation and the progression toward a senescent phenotype. Published 04 August 2020. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

The mevalonic acid biosynthetic pathway maintains canonical cell activation triggers that link intermediary metabolism to T lymphocyte differentiation. 02 August 2020 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

The master regulator of protein translation, mTORC, is itself regulated by the stress-induced AMPK pathway. Rapamycin and semi-selective drugs regulating  AMPK may reduce glioblastoma progression and this observation helps to advance a theory for healthy longevity that requires a reduction in anabolism. By Dr Daniel J. Guerra. Published 01 August 2020 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message