Metadichol® induced expression of neuronal transcription factors with Human fibroblast Dermal cells

Raghavan, P.R.

doi:10.21203/rs.3.rs-1983481/v1

Cited by 8 publications

(5 citation statements)

References 72 publications

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“…Forester et al [30][31] suggested that the liganded vitamin D receptor (VDR) upregulates Klotho via vitamin D response elements (VDRE). Metadichol is a VDR inverse/protein agonist [32][33]. Among the consequences of the enhanced expression of Klotho is an increase in telomerase activity.…”

Section: Resultsmentioning

confidence: 99%

Metadichol ; An agonist that expresses anti-aging gene Klotho in various cell lines

Raghavan¹

2023

Preprint

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Klotho is a well-known tumor suppressor hormone that exhibits anti-cancer and anti-aging properties. Klotho levels are low or non-existent in cancer patients. Klotho protein levels decrease with aging; maintaining consistent levels may prevent disease and promote healthier aging. Metadichol is a nano emulsion of long-chain alcohols C26, C28, and C30, of which C-28 constitutes over 85%. Any small molecule that can elevate Klotho can, in principle, help reverse many diseases in which Klotho levels are low. Previously, we showed that treatment of the pancreatic cancer cell lines PANC1, MIA-PACA, and COLO-205, combined with Metadichol, a lipid emulsion consisting of long-chain alcohols at 1-100 pg/mL concentrations, resulted in a 4- to 10-fold increase in Klotho expression as determined by qRT-PCR, This study aimed to demonstrate that Metadichol promotes Klotho expression in a wide variety of cell lines, such as primary cancer, stem, and somatic cell lines. Cells were treated with various concentrations of Metadichol ranging from 1 pg to 1 µg. Three to fifteen fold increase in Klotho expression was observed compared with baseline, as measured by qRT-PCR and qualified by western blot analysis. Metadichol is a natural agonist of Klotho expression and is non-toxic at levels up to 5000 mg/kg in rats. and has a potential therapeutic role in cancer and reversing aging.

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Section: Resultsmentioning

confidence: 99%

Metadichol ; An agonist that expresses anti-aging gene Klotho in various cell lines

Raghavan¹

2023

Preprint

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“…Metadichol targets these genes as well (64 Metadichol has all the characteristics needed to reverse aging-related diseases. Based on our previous work (64)(65)(66)(67). Metadichol ® represents the rst of a class of safe therapeutics that target MRGs affecting multiple genes, pathways, and diseases…”

Section: Resultsmentioning

confidence: 99%

Metadichol® a Sirtuin Modulator for Anti-Aging Therapies

Raghavan¹

2023

Preprint

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There are seven sirtuin genes in humans that encode seven sirtuin enzymes (SIRT1–7), each of which has unique functions and subcellular locations. Sirtuins are NAD+-dependent protein deacetylases that play a significant role in physiological processes such as energy metabolism, stress responses, DNA repair, and gene expression. Sirtuins are essential targets for aging-related diseases such as type 2 diabetes, inflammatory diseases, and neurodegenerative disorders. However, finding a single molecule that can activate all seven sirtuin genes is challenging because each isoform has a unique structure, substrates, and regulatory mechanisms. Most known sirtuin activators are specific for SIRT1, the most studied isoform of the sirtuin family. Here, we report that Metadichol®, a nano-emulsion of long-chain alcohols, induces 3- to 15-fold expression of all SIRT1–7 genes in human dermal fibroblasts when used in concentrations ranging from 1 pg/mL to 100 ng/mL. SIRT3 and FOXO1 gene expressions were 15-fold higher than those after treatment with Metadichol®. In addition, KL, FOXO1, TERT, and TP53 exhibited increased expression. Sirtuins and the four genes regulate aging, metabolism, and DNA repair and are age-related diseases like cancer, cardiovascular disease, and diabetes. All of these genes play essential roles in improving the quality of life as we age.

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“…Metadichol ® represents the rst of a safe class of therapeutics that target multiple genes, pathways [59][60][61][62] and multiple diseases, which points to importanceof a relevance of the network-based approach. 63…”

Section: Therapeutic Strategymentioning

confidence: 99%

Metadichol induced differentiation of pancreatic ductal cells (PANC-1) into insulin-producing cells

Raghavan

2023

Preprint

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Endocrine gene expression in PANC-1, a type of pancreatic cancer cell, has been studied in the context of their potential to be reprogrammed toward a normal, differentiated state. Alkaline phosphatase activity has also been shown in pluripotent stem cells to differentiate between feeder and parental cells in reprogramming experiments. Metadichol®-based cell programming holds promise as a versatile and potentially safer approach for manipulating cellular behavior without the use of viral vectors, gating, or CRISPR. This study investigated the multifold increase in the gene expression of CA9, GCG, INS MAFA, NEUROD1, NGN3, NKX2-2, PAX6: PDX1, SLC2A2, FOXO1, and SIRT1 using qRT‒PCR. These genes regulate endocrine cell development in the pancreas and are involved in insulin and glucagon secretion. Gene network analysis is presented to show how Metadichol-induced expression leads to a closed loop feedback network and biological process that would help in mitigating diabetes and other related disorders.

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Metadichol® induced expression of neuronal transcription factors with Human fibroblast Dermal cells

Cited by 8 publications

References 72 publications

Metadichol ; An agonist that expresses anti-aging gene Klotho in various cell lines

Metadichol ; An agonist that expresses anti-aging gene Klotho in various cell lines

Metadichol® a Sirtuin Modulator for Anti-Aging Therapies

Metadichol induced differentiation of pancreatic ductal cells (PANC-1) into insulin-producing cells

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