Abstract
Inflammaging is a chronic, low-grade inflammatory state that contributes to age-related diseases, including cardiovascular disorders, osteoporosis, neurodegeneration, and cancer. This process involves immunosenescence, oxidative stress, and immune aging, all of which contribute to the breakdown of immune tolerance and the onset of autoimmune disorders. Aloe vera (AV) has recently gained attention for its immunomodulatory, anti-inflammatory, and antioxidant properties. This review explores the effects of AV extracts and anthraquinones (e.g., aloe-emodin, emodin, aloin) on key inflammaging-driven mechanisms in autoimmunity. Our analysis highlights AV's ability to regulate hormone balance, autoantibody production, and cytokine/chemokine signaling (such as interleukin-1β, tumor necrosis factor-α, and interferon-γ). It modulates inflammatory pathways, including mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), thereby inhibiting nuclear factor kappa-light-chain-enhancer of activated B-cell (NF-κB) activation. Additionally, AV enhances antioxidant defenses and restores immune balance by reducing Th1/Th17 subsets while promoting Th2-mediated regulation. Notably, AV also modulates inflammasome-mediated mechanisms and counteracts immunosenescence, which is driven by autophagy-related processes. These effects position AV as a potential integrative approach to mitigating inflammaging-driven autoimmunity. Furthermore, as inflammaging is increasingly recognized in onco-hematological diseases, AV-based strategies may offer novel therapeutic avenues. Future studies should focus on clinical validation, optimizing formulations, and expanding applications to broader age-related and immune-mediated disorders.