Stem cells lose their regenerative potency through five interconnected molecular pathways that accelerate with age. Cellular stress accumulation disrupts DNA integrity and protein folding, while epigenetic drift alters chromatin structure and gene expression patterns essential for stem cell identity. Telomere erosion limits replication cycles, and metabolic dysfunction impairs energy production and cellular cleanup mechanisms through autophagy. Additionally, senescent cells release inflammatory signals that damage surrounding stem cell niches. This comprehensive framework reveals how aging transforms the body's cellular repair system into a source of dysfunction. The interconnected nature of these pathways suggests that targeting multiple mechanisms simultaneously may be more effective than addressing individual aging hallmarks. For longevity-focused adults, this research supports interventions that reduce oxidative stress, maintain metabolic flexibility, and preserve cellular energy production. The review's emphasis on epigenetic changes also highlights the potential reversibility of some aging processes, as epigenetic modifications can theoretically be reset. However, the complexity of these interacting systems means that stem cell rejuvenation therapies will likely require sophisticated multi-target approaches rather than simple supplementation strategies.