Authentic Biochemistry

Cell fate from Either ageing associated senescence to programmed cell death OR cell proliferation is finely tuned to the splice variant  expression of Cell Cycle dependent kinase inhibitors and the relative production of pro-inflammatory cytokines under the synchrony of DNA Damage Repair (DDR), telomerase expression decline, and the protective role of the Senescence Associated Secretory Phenotype (SASP).

Dr. Daniel J. Guerra. 06 Dec 2021 Authentic Biochemistry Productions

References:

Oncotarget. 2013 Oct; 4(10): 1552–1553

Cancer Rep Rev. 2018 Mar; 2(2): 10

Nat Med. 2017 Jun; 23(6): 775–781

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

EBioMedicine 2016 830-39DOI: (10.1016/j.ebiom.2016.04.017

Age Ageing, Volume 48, Issue 6, November 2019, Pages 776–782

Biomedicines. 2020 Aug 6;8(8):277

Dr. Guerra authentically arrives at the inveighing cancer paradigm contribution to the sickness unto death.

Nutrients. 2020 Mar; 12(3): 622.

Biochemistry and Cell Biology of Ageing: Part II Clinical Science. 2019. pp 21-43.The Immune System and Its Dysregulation with Aging

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.

 Phosphorylated ITAMs function as a molecular platform  for  tandem SH2 domains located on  the tyrosine kinase Zap-70, initially activated by Lck. 

Lck kinase activity is regulated at  two canonical  phosphorylation sites Tyr394 and Tyr505, wherein auto-transphosphorylation of Tyr394 in the kinase domain erupts a relaxed/active conformation but phosphorylation of Tyr505, located at the C-terminus, by the tyrosine kinase Csk results in an inactive enzyme.

References

Longev Healthspan. 2012; 1: 6

SCIENCE ADVANCES•19 Jun 2019•Vol 5, Issue 6

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. 2001 Sep 15;122(13):1413-30

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

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.