Advanced glycation end products (AGEs) are a group of compounds formed through non-enzymatic reactions between reducing sugars and proteins, lipids, or nucleic acids. AGEs can be generated in the body or introduced through dietary sources and smoking. Recent clinical and animal studies have highlighted the significant role of AGEs in various health conditions. These compounds accumulate in nearly all mammalian tissues and are associated with a range of diseases, including diabetes and its complications, cardiovascular disease, and neurodegeneration. This review summarizes the major diseases linked to AGE accumulation, presenting both clinical and experimental evidence. The pathologies induced by AGEs share common mechanisms across different organs, primarily involving oxidative stress, chronic inflammation, and direct protein cross-linking. Interventions targeting AGE-related diseases focus on inhibiting AGE formation using synthetic or natural antioxidants, as well as reducing dietary AGE intake through lifestyle modifications. AGEs are recognized as significant risk factors that impact health and accelerate aging, particularly in individuals with hyperglycemia. Monitoring AGE level and implementing nutritional interventions can help maintain overall health and reduce the risk of AGE-related complications.
Chronic inflammation accelerates the aging process, and targeted clearance of senescent cells shows potential in alleviating age-related decline. PCC1, a potent senescent cell clearance agent in grape seed extract (GSE), has limited applications due to its low oral bioavailability. This study introduced a novel GSE formulation, Natural Senolytics PCC1 (NSPCC1), which significantly enhanced PCC1 absorption and metabolic characteristics. Validation in two mouse aging models demonstrated that oral administration of NSPCC1 markedly extended lifespan and promoted healthy aging. The formulation improved the capacity for hematopoietic stem/progenitor cell differentiation and reduced age-related myeloid cell bias. Comprehensive histological analysis revealed attenuated aging phenotypes in bone marrow and skin, improved peripheral blood erythroid parameters, and a partial increase in blood antioxidant capacity, alongside reduced M1 macrophage infiltration and fibrosis in liver, kidney, and lung tissues. These effects were validated through histological assessments, including H&E, Masson, F4/80, and iNOS staining. This study highlighted the pivotal role of hematopoietic stem cells in aging and established NSPCC1 as a promising natural intervention for age-related pathologies. Its enhanced efficacy lays the groundwork for deeper exploration of natural products in aging biology and provides crucial support for the development of safe and effective anti-aging therapies.