Authentic Biochemistry

The pineal endocrine hormone melatonin proximally decreasesIL-1β-induced MMP production by inhibiting Sirt1-dependent NAMPT and NFAT5 signaling in chondrocytes;  since autoinflammatory  Osteoarthritis (OA) is a degenerative joint (cartilage degradation) disease linked to human aging and Interleukin-1β  contributes to OA pathogenesis by enhancing oxidative stress and inflammation the...

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 se...

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  antagoni...

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...

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...

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...

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...

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...

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 lymphoproli...

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 Bioc...

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. Immunosene...

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,...

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 rol...

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. Please join our Patreon and contribute to Authentic Biochemistry today!

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

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 .

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! 

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.

The mevalonic acid biosynthetic pathway maintains canonical cell activation triggers that link intermediary metabolism to T lymphocyte differentiation. 02 August 2020

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

In this lecture I gather some of the notable molecular components of age-related decline and the contrarion opposition imposed by cell proliferation. Published 30 July 2020. DJGPhD. 

Dr Dan Guerra examines nutritional restriction and exercise in combination with anti-diabetic drugs to impact the aging process. Published 27 July 2020.

Dr Guerra explains chain initiation, propagation and  termination during  lipid oxidation and the REDOX reactions of the electron transport chain  as a lead in to enzymatic oxidations and the plasticity of immune linked senescence. 26 July 2020.

Dr Guerra lays out the reduction of molecular oxygen to water and the accumulation of intermediate free radical oxygen species that are reduced via enzymatic activity and anti=oxidants. Aging is related to the auto-oxidation of nucleic acids, protein and significantly, membrane unsaturated molecular species of lipids. 24 July 2020