Vitamin D deficiency and Premature Aging
How are your Telomeres going ? Do Jabbees' Necks tell us about the Endotoxin levels circulating in their blood ? Anti-aging Gurus might be interested.
My friend Rob and I have been discussing the Necks of prominent Covid19 Jabbees for about a year now, as we have spent a great deal of time looking at famous people who have promoted or enforced Mandatory Jabbing.
We think they are aging faster than us (of pure unjabbed blood) and research from Saudi Arabia and UK supports our hypothesis. Rather than post pictures of people we have watched decline rapidly, here is some boring real-world data.1
Note these are log/log graphs. The caption, edited, reads:
Fig. 2. Association of normalized values of TL (Telomere Length) and log Endotoxin a) all subjects, b) non-T2DM, and c) T2DM (Type 2 Diabetes Mellitus). The trend line shows inverse correlation between log Endotoxin and TL.
Blood samples were taken from 775 Saudi adults visiting different primary care centers in Riyadh. Telomere Length was derived from peripheral blood mononuclear cells, analyzed by Quantitative Real-Time Polymerase Chain Reaction and circulating Endotoxin levels by Limulus Amebocyte Lysate assay.
Link to Vitamin D = 25(OH)D
A significant lower TL was observed in the non-obese T2DM group as compared with their non-obese, non-T2DM counterparts (p = 0.002). Significant inverse associations between TL, Endotoxin and Endotoxin activity were observed in the cohort with obesity. Regression analysis showed that endotoxin was a significant predictor for TL in all subjects and even after stratification according to subgroups; with variances perceived in circulating TL stronger among non-T2DM obese (10%; p = 0.003) than non-T2DM non-obese (12%; p = 0.007). Also, in the non-T2DM group, TL and HDL-cholesterol predicted 29% of the variances perceived in 25(OH)D (p < 0.001). Taken together these findings show that circulating Endotoxin and 25(OH)D are associated with premature biological ageing influenced by adiposity and metabolic state.
This work was preceded by studies of Obesty and Insulin Resistance in Arab youth linked to Inflammation in the same research group.2
Mechanisms of Endotoxin Induced Aging
In 1999 Bruunsgaard reported shorter Telomeres in Human lymphocytes after exercise3, however more in-depth discussion of Endotoxemia from exercise will have to wait for another day.
Interesting 2023 free paper by Abdelgawad and coworkers investigated Endothelial Cell (EC) Senescence (Aging) in Cancer patients treated with Doxorubicin.4 Senescent ECs exhibit a hyper-inflammatory response to Endotoxin (Lipopolysachharide LPS).
They point to a 2009 paper by Spallarossa and coworkers5 who found Doxorubicin induces senescence or apoptosis in rat neonatal cardiomyocytes by regulating the expression levels of the Telomere Binding factors 1 and 2.
Abdelgawad and coworkers also point us to the 2021 work of Raj et al. who showed6 Vitamin D3 (Cholecalciferol) and Metformin protect against Endotoxin (Lipopolysaccharide)-induced Endothelial Dysfunction and Senescence by modulating Sirtuin-1 and Protein Arginine Methyltransferase-1.
In 2007 it was found that Age-related changes in Rat Hippocampus were ameliorated by treatment with Vitamin D3 and Dexamethasone.7 They blocked the Endotoxin-increased MHCII mRNA and IL-1β concentration. The IL-1β-induced increases in activation of JNK and Caspase 3 in cultured neurons were also reversed by treatment with Dexamethasone and Vitamin D3.
cGAS-STING pathway8 has been shown to be activated by dysfunctional Telomeres.9
Quick Summary
Endotoxin Jab > Gut Dysbiosis > Cellular Senescence accelerated by Endotoxin > Premature Aging.
Related Vitamin D Endotoxin reading
Previous articles include references.101112
GMO specialists recognize Endotoxin as a major problem when the want to play with artificial “Human” Chromosomes and Teleomeres.13
Happy to add more references found by my subscribers.
Nasser M Al-Daghri, Shaun Sabico, Mohammed G A Ansari, Saba Abdi, Gyanendra Tripathi, George P Chrousos, Philip G McTernan. 2022. Endotoxemia, vitamin D and premature biological ageing in Arab adults with different metabolic states. https://www.sciencedirect.com/science/article/pii/S1319562X2200184X
OS Al-Attas, N Al-Daghri, A Bamakhramah, S Shaun Sabico, P McTernan, TT-K Huang. 2010. Telomere length in relation to insulin resistance, inflammation and obesity among Arab youth. https://onlinelibrary.wiley.com/doi/10.1111/j.1651-2227.2010.01720.x
Bruunsgaard H, Jensen MS, Schjerling P, Halkjaer-Kristensen J, Ogawa K, Skinhoj P, and Pedersen BK. Exercise induces recruitment of lymphocytes with an activated phenotype and short telomeres in young and elderly humans. Life Sci 65: 2623-2633.
Ibrahim Y Abdelgawad, Kevin Agostinucci, Bushra Sadaf, Marianne K O Grant, Beshay N Zordoky. 2023. Metformin mitigates SASP secretion and LPS-triggered hyper-inflammation in Doxorubicin-induced senescent endothelial cells. https://www.frontiersin.org/journals/aging/articles/10.3389/fragi.2023.1170434/full
Paolo Spallarossa, Paola Altieri, Concetta Aloi, Silvano Garibaldi, Chiara Barisione, Giorgio Ghigliotti, Giuseppina Fugazza, Antonio Barsotti, and Claudio Brunelli. 2009. Doxorubicin induces senescence or apoptosis in rat neonatal cardiomyocytes by regulating the expression levels of the telomere binding factors 1 and 2. Am J Physiol Heart Circ Physiol 297: H2169–H2181. doi:10.1152/ajpheart.00068.2009
Vijay Raj, Suganya Natarajan, Marimuthu C, Suvro Chatterjee, Mohankumar Ramasamy, Ganesh Munuswamy Ramanujam, Mariadhas Valan Arasu, Naif Abdullah Al-Dhabi, Ki Choon Choi, Jesu Arockiaraj, Kanchana Karuppiah. 2021. Cholecalciferol and metformin protect against lipopolysaccharide-induced endothelial dysfunction and senescence by modulating sirtuin-1 and protein arginine methyltransferase-1. https://www.sciencedirect.com/science/article/abs/pii/S0014299921006877
Michelle Moore, Alessia Piazza, Yvonne Nolan, Marina A. Lynch. 2007. Treatment with dexamethasone and vitamin D3 attenuates neuroinflammatory age-related changes in rat hippocampus. https://onlinelibrary.wiley.com/doi/abs/10.1002/syn.20433
Salim Abdisalaam, Souparno Bhattacharya, Shibani Mukherjee, Debapriya Sinha, Kalayarasan Srinivasan, Mingrui Zhu, Esra A. Akbay, Hesham A. Sadek, Jerry W. Shay, and Aroumougame Asaithamby. 2020. Dysfunctional telomeres trigger cellular senescence mediated by cyclic GMP-AMP synthase. J. Biol. Chem. (2020) 295(32) 11144–11160
Nicholas C. O. Lee, Nikolai S. Petrov, Vladimir Larionov, and Natalay Kouprina. 2011. Assembly of Multiple Full-Size Genes or Genomic DNA Fragments on Human Artificial Chromosomes Using the Iterative Integration System. Current Protocols, 1, e316. doi: 10.1002/cpz1.316
Good levels of circulating 25-hydroxyvitamin D - at least 50 ng/mL 125 nmol/L - are needed to supply the intracrine (inside each cell) and paracrine (to nearby cells, typically of different types) signaling systems of many cell types. I normally mention that many types of immune cell rely on these signaling systems in order to respond to their changing circumstances, but there is an unknown, but probably large (dozens to hundreds), number of cell types which are not involved in immunity for which this is true.
To what extent telomere protection's apparent dependence on good 25-hydroxyvitamin D levels are due to immune cells or to processes in cell types not directly involved in immune responses is probably not known. It doesn't really matter. The body is much healthier with 50 to (for the great majority of people) 100 ng/mL circulating 25-hydroxyvitamin D than with the 5 to 30 or so ng/mL (12.5 to 75 nmol/L) levels of most people who do not supplement vitamin D3 properly and have not recently had extensive UV-B exposure of ideally white skin.
Without vitamin D3 supplements in quantities which are small, but 5 or more times the tiny amounts governments and many doctors recommend, the body has only a fraction of the 25-hydroxyvitamin D (made in the liver from vitamin D3) it needs to run the immune system properly. A "balanced diet" doesn't help, since there is very little vitamin D3/2 in food, whether it is fortified with vitamin D3 (or more likely the more stable but less effective vitamin D2). UV-B skin exposure can produce lots of vitamin D3, but it is difficult to obtain all year round and always damages DNA, so raising the risk of skin cancer.
You can read the research via pages linked to from my "5 neglected nutrients" site https://5nn.info. This includes recommendations from New Jersey-based Professor of Medicine Sunil Wimalawansa on how much vitamin D3 to supplement to attain the 125 nmol/L (50 ng/mL) 25-hydroxyvitamin D (as measured in "vitamin D" blood tests), to ensure that the immune system can work properly, which greatly reduces the risks of serious illnesses of many kinds, including neurodegeneration and sepsis, as well as protecting against problems in pregnancy and early childhood development.
Vitamin D3 cholecalciferol is hydroxylated, primarily in the liver, to 25-hydroxyvitamin D (calcifediol, or "calcidiol") which has a half life in the bloodstream of weeks to months. Neither are hormones. These are not signaling molecules. For a description of 25-hydroxyvitamin D >> calcitriol (1,25-dihydroxyvitamin D) intracrine and paracrine signalling, please see https://vitamindstopscovid.info/00-evi/.
A more detailed explanation of these signaling systems is at: https://vitamindstopscovid.info/02-intracrine/.