Also

Magnesium is indirectly involved in Klotho gene protein production. When blood serum calcium levels are somewhat below normal, magnesium reduces parathyroid secretion and increases parathyroid calcium cell receptor, the vitamin D receptor and Klotho gene protein. This suggests calcium intake should be limited and magnesium shortages should be avoided for healthy aging. (Nephrology Transplantation, February 2014).

Delta sleep enhances growth hormone secretion which increases Klotho.. Rosemary, tryptophan, 5HTP plus GABA, ashwagandha, and gemnostemma enhance Delta sleep.

https://www.ncbi.nlm.nih.gov/pubmed/25086986 Klotho: a novel biomarker for cancer Klotho has biological activity that includes regulatory effects on general metabolism and a more specific effect on mineral metabolism that correlates with its effect on aging. Klotho serves as a co-receptor for fibroblast growth factor (FGF), but it also functions as a humoral factor that regulates cell survival and proliferation, vitamin D metabolism, and calcium and phosphate homeostasis and may serve as a potential tumor suppressor. Moreover, Klotho protects against several pathogenic processes in a FGF23-independent manner. These processes include cancer metastasis, vascular calcification, and renal fibrosis. This review covers the recent advances in Klotho research and discusses novel Klotho-dependent mechanisms that are clinically relevant in aging and age-related diseases

https://www.ncbi.nlm.nih.gov/pubmed/27733247
Klotho response to treatment with growth hormone and the role of IGF-I as a mediator.
Klotho levels increased during GH treatment of pediatric GHD patients. This increase was associated with an increase in IGF-I levels. Furthermore, we showed, for the first time, a direct role of IGF-I in the regulation of klotho’s shedding which depends on activation of the AKT-mTOR pathway. Our findings add further support for the close association between klotho and the GH/IGF-I axis
Rhein reverses Klotho repression via promoter demethylation and protects against kidney and bone injuries in mice with chronic kidney disease

https://www.ncbi.nlm.nih.gov/pubmed/15665504 Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice. Klotho protein in kidney is implicated in calcium homeostasis which regulates localization of sodium phosphate cotransporters via parathyroid hormone. Klotho proteins not only function as a humoral factor, but also are implicated in hormonal regulation, which may explain why mutation of klotho gene results in a variety of phenotypes.

https://www.ncbi.nlm.nih.gov/pubmed/18259951 Klotho expression in epithelial ovarian cancer and its association with insulin-like growth factors and disease progression. In conclusion, Klotho expression is associated with epithelial ovarian cancer progression, and the protein may serve as an independent marker for ovarian cancer prognosis. Klotho’s role in cancer warrants further elucidation.

https://www.ncbi.nlm.nih.gov/pubmed/26499380 Overexpression of Klotho suppresses liver cancer progression and induces cell apoptosis by negatively regulating wnt/β-catenin signaling pathway.

https://www.ncbi.nlm.nih.gov/pubmed/25086986 Klotho: a novel biomarker for cancer. Downregulation of Klotho was found in several cancers, such as pancreatic cancer, HCC, and other tumors. Downregulation of Klotho resulted in promoted proliferation and reduced apoptosis of cancer cells. The relevant mechanisms include the fibroblast growth factor signaling, the insulin-like growth factor 1 receptor pathway, and the Wnt/β-catenin signaling pathway. Furthermore, the Klotho protein hopefully provides new insights into cancer target treatment..

https://www.ncbi.nlm.nih.gov/pubmed/26237271 Klotho: a tumor suppressor and modulator of the Wnt/β-catenin pathway in human hepatocellular carcinomaThese data suggest that klotho acts as a tumor suppressor and an inhibitor of the Wnt/β-catenin pathway in HCC, and moreover, that soluble klotho is a potential serum biomarker for HCC.

https://www.ncbi.nlm.nih.gov/pubmed/27377727 Vitamin D: a custodian of cell signaling stability in health and disease..

https://www.ncbi.nlm.nih.gov/pubmed/26009175 Vitamin D, reactive oxygen species and calcium signalling in ageing and disease. Vitamin D is a hormone that maintains healthy cells. It functions by regulating the low resting levels of cell signalling components such as Ca(2+) and reactive oxygen species (ROS). Its role in maintaining phenotypic stability of these signalling pathways depends on the ability of vitamin D to control the expression of those components that act to reduce the levels of both Ca(2+) and ROS. This regulatory role of vitamin D is supported by both Klotho and Nrf2. A decline in the vitamin D/Klotho/Nrf2 regulatory network may enhance the ageing process, and this is well illustrated by the age-related decline in cognition in rats that can be reversed by administering vitamin D. A deficiency in vitamin D has also been linked to two of the major diseases in man: heart disease and Alzheimer’s disease).

https://asu.pure.elsevier.com/en/publications/125-dihydroxyvitamin-d-and-klotho-a-tale-of-two-renal-hormones-co 1,25-Dihydroxyvitamin D3 (1,25D) is the renal metabolite of vitamin D that signals through binding to the nuclear vitamin D receptor (VDR). The ligand-receptor complex transcriptionally regulates genes encoding factors stimulating calcium and phosphate absorption plus bone remodeling, maintaining a skeleton with reduced risk of age-related osteoporotic fractures. 1,25D/VDR signaling exerts feedback control of Ca/PO4 via regulation of FGF23, klotho, and CYP24A1 to prevent age-related, ectopic calcification, fibrosis, and associated pathologies. Vitamin D also elicits xenobiotic detoxification, oxidative stress reduction, neuroprotective functions, antimicrobial defense, immunoregulation, anti-inflammatory/anticancer actions, and cardiovascular benefits. Many of the healthspan advantages conferred by 1,25D are promulgated by its induction of klotho, a renal hormone that is an anti-aging enzyme/coreceptor that protects against skin atrophy, osteopenia, hyperphosphatemia, endothelial dysfunction, cognitive defects, neurodegenerative disorders, and impaired hearing. In addition to the high-affinity 1,25D hormone, low-affinity nutritional VDR ligands including curcumin, polyunsaturated fatty acids, and anthocyanidins initiate VDR signaling, whereas the longevity principles resveratrol and SIRT1 potentiate VDR signaling. 1,25D exerts actions against neural excitotoxicity and induces serotonin mood elevation to support cognitive function and prosocial behavior. Together, 1,25D and klotho maintain the molecular signaling systems that promote growth (p21), development (Wnt), antioxidation (Nrf2/FOXO), and homeostasis (FGF23) in tissues crucial for normal physiology, while simultaneously guarding against malignancy and degeneration. Therefore, liganded-VDR modulates the expression of a “fountain of youth” array of genes, with the klotho target emerging as a major player in the facilitation of health span by delaying the chronic diseases of aging.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711388/ THE ANTI-AGING PROTEIN KLOTHO ENHANCES OLIGODENDROCYTE MATURATION AND MYELINATION OF THE CENTRAL NERVOUS SYSTEM

http://www.ies.org.il/annual12/Session4Hormones.pdf KLOTHO, A NOVEL REGULATOR OF SOMATOTROPE PROLIFERATION AND HORMONE SECRETION
Our findings indicate, for the first time, a role for klotho and bFGF in somatotroph proliferation and GH secretion.

https://www.ncbi.nlm.nih.gov/pubmed/24939736 The aging suppressor Klotho: a potential regulator of growth hormone secretion.

https://www.ncbi.nlm.nih.gov/pubmed/27881156 Klotho sensitive regulation of dendritic cell functions by vitamin E. The up-regulation of klotho by VitE could contribute to the inhibitory effects of VitE on NF-κB-mediated DC functional maturation. The events might contribute to immunotherapeutic effect of VitE on the pathophysiology of klotho-related disease.

https://www.ncbi.nlm.nih.gov/pubmed/27721584
The Three Sisters of Fate in Multiple Sclerosis: Klotho (Clotho), Fibroblast Growth Factor-23 (Lachesis), and Vitamin D (Atropos). Klotho, which is secreted from Choroid Plexus, could be a response to the inflammatory condition in MS. Elevated FGF-23 levels suppress 1α-hydroxylase and upregulates 24α-hydroxylase, which results in a decrease in 1,25-(OH)2D3 levels. Thus, the neuroprotective and immunomodulatory effects of vitamin D might not be seen in MS patients.

https://www.ncbi.nlm.nih.gov/pubmed/28540270 FGF-23, Klotho and Vitamin D Levels in Scleroderma.
The decreased serum Klotho, 25-OH Vit D, and increased iPTH levels in the scleroderma patients may be associated with the pathogenesis of this disease and could be considered a future therapeutic target.

The levels of Klotho in the brain showed a striking decrease with aging. Studies led to the observation that secretion of Klotho is regulated by insulin. They found that insulin, a hormone usually associated with diabetes, increases significantly the levels of secreted Klotho. The reason this finding is important is because excess insulin has been previously implicated in a biochemical pathway that is associated with a decreased life span and elevated oxidative stress. In addition, this observation provides a potentially pivotal link between Klotho and sugar metabolism, and raises an intriguing relationship between Klotho and type II diabetes, commonly known as late onset diabetes. The authors are proposing a novel mechanism of action for Klotho whereby insulin increases Klotho secretion, i.e., activity, and in turn, the secreted Klotho inhibits insulin’s actions in the cell, which are known to be detrimental when insulin is in excess.

Thanks, man. Novolin R was used in one of the studies. You should be able to buy it without a prescription at Walmart. Just go to the pharmacy and ask them for it. Here is the study that used it. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804944/

“Fasting subjects came on five separate mornings, one to six weeks apart, to receive saline or one of four insulin doses (10, 20, 40, or 60 IU) in randomized counterbalanced order. An initial blood sample was obtained and subjects were placed in a supine position with the head tilted back. One-hundred μL of insulin (Novolin R, Novo Nordisk, Princeton, NJ, USA) or saline were administered with a needle-less syringe into alternating nostrils for a total volume of 600 μL at each visit. One-hundred μL of insulin corresponded to 10 IU; saline was administered as needed at insulin visits to achieve the total study drug volume of 600 μL. Subjects were instructed to sniff following administration to facilitate transport of insulin into the nasal cavity. Subjects rested for 15-minutes. “

Any links to products?

Looks really interesting. Great find!

It’s pretty amazing stuff and the research on humans is quite extensive. My hope is that it can really help many of your clients with depression, insulin resistance, and thyroid issues. The research is going to blow you away. =)
http://www.ncbi.nlm.nih.gov/pubmed/25750079

Interesting!

And also:
Probiotics
Carbs to increase Insulin
PPARgamma activators
Statins/Red yeast rice
Activated charcoal
Gentian root extract

Very interesting nonetheless.