KLOTHO

Klotho is an anti-aging protein that is mostly secreted by the kidneys, the brain, and the thyroid. It plays a significant role in regulating kidney function and vascular health. Klotho gene is named after "the Spinner" (Clotho from Greek mythology), the goddess who spins the thread of life. Klotho is a transmembrane protein known to be a co-receptor for Fibroblast Growth Factor-23. Klotho gene is expressed in a variety of tissues changes in the levels are associated with many diseases. Klotho is a tumor suppressor in breast cancer and its expression is reduced in human pancreatic adenocarcinoma, and treatment with klotho inhibits the growth of pancreatic cancer cells in vitro and in vivo.

Growing evidence suggests that an increase in KL expression may be beneficial for age-related diseases such as arteriosclerosis and diabetes. It remains a challenge today to induce Klotho expression. Herein we show that treating pancreatic cancer cells PANC1, MIAPACA and COLO-205 with Metadichol ® a novel food based lipid emulsion of long chain alcohols at picogram/ml, concentration led to a 4-10 fold increase in Klotho expression as seen quantitative RT-PCR. These results suggest the use of Metadichol ® given its constituents that are present in foods we consume every day is a novel therapeutic intervention for pancreatic cancer and other diseases.

Caloric restriction (CR), renin angiotensin system blockade (RAS-bl), and rapamycin-mediated mechanistic target of rapamycin (mTOR) inhibition increase survival and retard aging across species. Previously, we have summarized CR and RAS-bl's converging effects, and the mitochondrial function changes associated with their physiological benefits. mTOR inhibition and enhanced sirtuin and KLOTHO signaling contribute to the benefits of CR in aging. mTORC1/mTORC2 complexes contribute to cell growth and metabolic regulation. Prolonged mTORC1 activation may lead to age-related disease progression; thus, rapamycin-mediated mTOR inhibition and CR may extend lifespan and retard aging through mTORC1 interference. Sirtuins by deacetylating histone and transcription-related proteins modulate signaling and survival pathways and mitochondrial functioning. CR regulates several mammalian sirtuins favoring their role in aging regulation. KLOTHO/fibroblast growth factor 23 (FGF23) contribute to cont...

Data for fibroblast growth factor 23 (FGF23) and particularly for Klotho in healthy children are limited. We aimed to investigate the relationship between FGF23 and Klotho with age and TmP/GFR and to evaluate parameters that might affect FGF23 and Klotho. In 159 healthy children (82 boys) with a mean±SD age of 8.78±3.47years we measured FGF23 (intact FGF23/iFGF23 and C-terminal FGF23/cFGF23) and soluble aKlotho serum levels by ELISA. Mean±SD value for cFGF23, was 51.14±12.79 RU/ml whereas median (range) values for iFGF23 and Klotho were 35 (8.8, 120) pg/ml and 1945 (372, 5866) pg/ml respectively. Neither FGF23 nor Klotho were significantly associated with age. Pubertal children had higher Klotho than prepubertal (p<0.05), and girls had higher levels of cFGF23 (p<0.05) and Klotho (p<0.001) than boys. Serum phosphate and TmP/GFR were positively associated with cFGF23 (p<0.01 and p<0.001), iFGF23 (p<0.05 and p<0.001) and Klotho (p<0.05 and p<0.01). Klotho was...