MOLECULAR ATLAS OF AGING. META-GROUP 21. PLASMA ENZYME ACTIVITY: MIRROR REFLECTING SYSTEMIC COLLAPSE. INTEGRATIVE APPROACH IN THE CONTEXT OF THE THEORY OF META-ENVIRONMENTS AND META-REGULATORS

Relevance. Plasma enzyme activity is an integral mirror of systemic homeostasis, reflecting the integrity of cell membranes, synthetic liver function, bone remodeling, renin-angiotensin system activity, and proteolytic balance. Enzymes themselves are not the "cause" of aging — they are a reflection of systemic collapse: cell death, inflammation, metabolic disorders, membrane damage, and organ dysfunction. With age, the activity of many enzymes in plasma changes dramatically: lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) increase, cholinesterase falls, protease activity is restructured, angiotensin-converting enzyme (ACE) shows paradoxical dynamics (protein levels rise, activity falls), and ACE-2 increases significantly in the elderly, associated with fragility and metabolic disorders. These changes are correlated with biological age, cognitive decline, sarcopenia, and cardiovascular risk. Aim. To present age-related dysregulation of plasma enzyme activity as the twenty-first level of molecular aging — an integral mirror of systemic collapse, reflecting the depth of damage accumulated in the previous 20 groups, and at the same time a target for assessing the effectiveness of rejuvenating interventions. To substantiate the need for systemic restoration of tissue homeostasis to normalize the enzyme profile. Results. It was shown that with age, the activity of LDH, alkaline phosphatase, β-galactosidase, NAG, α-mannosidese, β-glucuronidase, glucose-6-phosphate dehydrogenase, adenosine deaminase and glutamate dehydrogenase increases with age. Cholinesterase activity decreases with age, and the pChE threshold value ≥ 99788 * U/L is associated with an increased risk of mild cognitive impairment and fragility. ACE exhibits a paradox: protein concentration is positively correlated with age, and enzymatic activity is inversely related to age, suggesting post-translational modifications. The concentration of ACE-2 protein is significantly higher in individuals >65 years of age compared to ≤45 years, and higher serum activity of ACE-2 is associated with worse physical function and fragility. The proteolytic balance shifts: plasmin activity increases, while MMP-9 and trypsin activity decreases with age, reflecting an imbalance between matrix degradation and its inhibition. A multimodal approach (Quatotron technique) to systemic restoration of tissue homeostasis, which automatically normalizes the enzyme profile, is proposed. Conclusion. The activity of plasma enzymes is the twenty-first level of molecular aging — an integral mirror of systemic collapse, reflecting the depth of age-related changes. Its normalization through the systemic control of meta-regulators opens up new opportunities for an objective assessment and achievement of healthy longevity.