Molecular Atlas of Aging. Meta-Group 13. Acute Phase Proteins and Metal Metabolism: A Delicate Balance That Breaks Down With Age. Integrative Approach in the Context of Meta-Medium Theory and Meta-Regulators

Relevance. Acute phase proteins (APPs) are a group of plasma proteins, the concentration of which changes by 25% or more in response to inflammation, infection, or injury. Normally, they perform protective functions: bind and transport metals, neutralize free hemoglobin, and suppress proteases. However, with age, against the background of chronic inflaming, their profile is distorted: some proteins become chronically elevated (ferritin, hepcidin, haptoglobin, ceruloplasmin), others decrease (albumin, transferrin). This shift turns the defense system into a tool of destruction: iron accumulates in tissues, catalyzing oxidative stress; copper loses control, contributing to neurodegeneration; zinc becomes deficient, weakening the immune system. Age-related metal imbalances are closely related to the phenomenon of ferroptosis, an iron-dependent form of cell death that contributes to tissue degeneration during aging. Aim. To present age-related dysregulation of acute phase proteins and metal metabolism as the thirteenth level of molecular aging — a switch between protection and toxicity, turning essential trace elements into damage factors that accelerate aging and all its diseases. To substantiate the need for systemic restoration of the balance of metals and acute phase proteins through the tuning of meta-regulators. Results. It has been shown that with age, the level of hepcidin, a key regulator of iron homeostasis, steadily increases under the influence of IL-6, creating a functional deficiency of iron with its normal reserves (anemia of chronic inflammation). Ferritin, being a positive protein of the acute phase, not only reflects inflammation, but also acts as an active trigger of the inflammatory process through the activation of NF-κB and NLRP3 inflammasome. Age-related inflammation causes epigenetic erosion of H4K20me1 in muscle stem cells, which induces ferroptosis through impaired iron metabolism and ROS accumulation. Ceruloplasmin, the main protein of copper transport with ferroxidase activity, contributes to iron overload and increased oxidative stress when dysregulated, worsening age-related heart dysfunction. Albumin, the main antioxidant in plasma, decreases with age, which is associated with an increased cardiovascular risk. Zinc deficiency acts as a key link between immunosensitivity and age-related diseases, exacerbating inflaming. A multimodal approach (the Quatotron technique) to physiologically restore the balance of metals and proteins of the acute phase by reducing systemic inflammation and optimizing nutritional support has been proposed. Conclusion. Acute phase proteins and metal metabolism are the thirteenth level of molecular aging, a system whose age-related imbalance converts essential trace elements into oxidative damage factors. Their systemic recovery through the control of meta-regulators opens up new opportunities for the prevention of age-associated diseases and healthy longevity.