Magnesium and Rapamycin in Long Covid and Longevity: A Mechanistic and Therapeutic Approach

A global shortfall in magnesium (Mg) is linked to long Covid and a shortened lifespan. Calcium (Ca) competes with Mg for the same receptor and the West ingests too much calcium and the East too little. An intake of Ca:Mg (weight to weight) close to 2:1 has been promulgated as the best measure of balance, but on a Western diet 3:2 might be a better target. RBC Mg sits at the nexus of intracellular Mg and serum Mg. This enables easy determination of serum Ca:Mg that reflects the intake ratio and general health status. Nutrient sensitive mTOR (mammalian target of rapamycin) and energy sensitive AMPK are inversely related. A balanced mTOR:AMPK ratio, is linked to healthy aging. Multiple studies in yeast, worms, flies, and rodents support the efficacy of rapamycin as a longevity agent. Any inhibition of mTOR by rapamycin can upregulate kinases that activate mTOR via alternate pathways. Whether this occurs with low-dose, intermittent rapamycin is unknown. But Mg is perfectly placed to block this. Rapamycin is a top down longevity agent, while Mg empowers longevity from the bottom up. They collaborate without competing. Efficacies may merge at the IFN-γ, indoleamine dioxygenase (IDO), kynurenine, aryl hydrocarbon receptor (AhR) interface. Persistence of any intracellular pathogen, e.g., SARS CoV2, can prolong IFN-γ activation of IDO. IDO metabolizes tryptophan (T) and upregulates the kynurenine (K) pathway, leaving less T for the indole (longevity biomarker) and serotonin pathways. An elevated K/T is linked to cancer, autoimmune disease, cardiovascular disease, dementia, diabetes, obesity, and chronic inflammation in general. Furthermore, Mg-dependent vitamin D immunomodulates IFN-γ.