The role of systemic acid-base imbalance in aging and cencer promotion

Age-related systemic acidification represents an active and regulated imbalance of acid-base homeostasis, driven by declining renal and respiratory function, leading to progressive metabolic acidosis characterized by lowered pH in blood and interstitial fluids. This condition creates a permissive environment for carcinogenesis by increasing tissue susceptibility to damage and facilitating the initiation and progression of cancer. Within the tumor microenvironment, an extremely acidic state arises due to aerobic glycolysis (the Warburg effect), which promotes malignancy aggressiveness, invasion, metastasis, and therapeutic resistance. Dietary factors, such as high acid load, alongside age-associated renal alterations, exacerbate this systemic acidification, thereby influencing cancer risk. Correction of acid-base balance through dietary modifications, metabolic interventions, and direct alkalinization with sodium bicarbonate can inhibit tumor progression and enhance the efficacy of chemotherapy and immunotherapy. Despite challenges related to the tolerability of oral sodium bicarbonate formulations, localized parenteral administration demonstrates clinical efficacy, underscoring the critical role of pH normalization as a therapeutic strategy in malignancies. Thus, age-related acidification serves not only as a marker of physiological aging but also as an active contributor to cancer pathogenesis, revealing novel targets for the prevention and treatment of age-associated diseases.