Molecular Atlas of Aging. Meta-Group 9. Microbial and Uremic Toxins: A Silent Poison That Poisons Us From the Inside Out Integrative Approach in the Context of Meta-Medium Theory and Meta-Regulators

Relevance. With age, chronic internal poisoning increases in the body, due to two key processes: disruption of the intestinal barrier function ("leaky gut") and a decrease in renal filtration. These processes lead to the accumulation of microbial toxins (LPS lipopolysaccharide, TMAO trimethylamine oxide) and uremic toxins (indoxyl sulfate, p-cresyl sulfate, uric acid), which have been undermining the body for years, damaging the endothelium, disrupting metabolism, suppressing immunity, accelerating fibrosis and neurodegeneration. These toxins are "silent killers": they do not cause acute symptoms, but create a constant toxic background that intensifies all other breakdowns. Aim. To present microbial and uremic toxins as the ninth level of molecular aging – chronic internal poisoning, which makes all other aging processes more severe and recovery more difficult. To justify the need for systemic detoxification through the restoration of the intestinal barrier, normalization of the microbiota and improvement of renal function. Results. It has been shown that age-related disruption of the intestinal barrier leads to metabolic endotoxemia, a chronic increase in LPS in the blood, which activates TLR4/NF-κB, increasing inflamaging. TMAO, formed from choline and L-carnitine under the influence of intestinal bacteria, disrupts the reverse transport of cholesterol, activates inflammation, and promotes thrombosis. Uremic toxins (indoxyl sulfate, p-cresyl sulfate), which accumulate with age-related decrease in glomerular filtration rate, damage the endothelium through eNOS inhibition, activate NADPH oxidases, causing oxidative stress, and stimulate TGF-β-dependent fibrosis. With age, all these processes reinforce each other: LPS damages the kidneys, uremic toxins disrupt the intestinal barrier, creating a self-sustaining vicious circle. A multimodal approach (the Quatotron technique) to systemic detoxification through the restoration of the intestinal barrier, normalization of the microbiota and improvement of renal perfusion has been proposed. Conclusion. Microbial and uremic toxins are the ninth level of molecular aging – a chronic internal poison, without control of which rejuvenation is impossible. Their systemic elimination through the restoration of their own barrier and excretory mechanisms opens up new opportunities for the prevention of age-associated diseases and healthy longevity.