Metadichol® induced expression of Sirtuin family 1-7 in somatic and cancer cells

Abstract

The Sirtuins 1-7 family and Klotho (KL), Forkhead box protein O1 (FOXO1), telomerase reverse transcriptase (TERT), tumor suppressor p53 (TP53) and growth differentiation factor 11 (GDF11) regulate aging, metabolism, and DNA repair and are involved in age-related diseases such as cancer, cardiovascular disease, and diabetes. Seven sirtuin genes in humans encode seven sirtuin enzymes (SIRT1–7), each of which has unique functions and subcellular locations. Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases that play a significant role in physiological processes such as energy metabolism, stress responses, DNA repair, and gene expression and are potential targets for age-related diseases such as type 2 diabetes, inflammatory diseases, and neurodegenerative disorders. They also play a role in cancer by regulating critical cellular processes such as DNA repair and energy metabolism. Other genes, such as Klotho (KL), Forkhead box protein O1 (FOXO1), telomerase reverse transcriptase (TERT), tumor suppressor p53 (TP53) and growth differentiation factor 11 (GDF11), also regulate aging, metabolism, and DNA repair and are involved in age-related diseases such as cancer, cardiovascular disease, and diabetes. In addition, these proteins are closely related to sirtuins. A single molecule that can activate these five genes and sirtuin genes is challenging because each isoform has a unique structure, substrate, and regulatory mechanism. Most known sirtuin activators are specific for Sirtuin 1, the most studied isoform of the sirtuin family. This study was initiated based on previous work in which we showed that metadichol can express all nuclear receptors if it is possible to express all seven sirtuin families 1-7 using metadichol as a small molecule inducer. Herein, we report that at concentrations ranging from 1 pg/mL to 100 ng/mL, Metadichol®, a nanoemulsion of long-chain alcohols, induced the expression of the human Sirtuin 1-7 gene in dermal fibroblasts and a variety of cancer cells in a concentration-dependent manner and that KL, GDF11, telomerase, Foxo1 and P53 could have significant beneficial effects on mitigating age-related diseases. The results were quantified by using qRT‒PCR, and proteins were characterized using western blot techniques. The experimental procedure used is unique in that it did not involve the use of viruses or other gene insertion technique.