Aging is a multifaceted biological process shaped by intrinsic molecular mechanisms and extrinsic environmental factors, culminating in systemic functional decline and heightened vulnerability to age-related diseases. This review explores the hallmarks of physiological aging, including genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, cellular senescence, chronic inflammation, and gut dysbiosis. These interconnected pathways drive the gradual deterioration of cellular and tissue function, underpinning both natural aging and the onset of pathologies such as neurodegeneration, cardiovascular disease, and cancer. Environmental toxins including mycotoxins, heavy metals, chemical clastogens, and pollutants exacerbate aging by inducing oxidative stress, disrupting DNA repair, and altering epigenetic regulation, thereby accelerating cellular damage and systemic dysfunction. We highlight the role of mitochondrial dysfunction in senescence, the dual nature of autophagy in proteostasis, and the inflammatory cascade triggered by senescent cells, which perpetuates tissue degeneration. Furthermore, dysbiosis of the gut microbiota emerges as a critical modulator of aging, linking microbial imbalance to metabolic and immune dysregulation. By synthesizing current insights into these mechanisms, this review underscores the importance of targeting aging hallmarks to develop interventions that promote healthy longevity. Strategies such as dietary modulation, proteasome activation, and probiotic therapies demonstrate potential in mitigating age-related decline. Understanding the interplay between molecular pathways and environmental stressors offers a roadmap for innovative therapies aimed at decelerating aging processes, enhancing health span and reducing the burden of age-associated diseases. This holistic perspective bridges fundamental aging biology with translational applications, emphasizing the urgency of interdisciplinary approaches to address the challenges of global population aging. |
