A shift in architecture of aging: Cellular pathways and molecular networks

Aging is a multifactorial process driven by interconnected hallmarks that progressively compromise cellular and tissue function. Among the most recognized contributors are genomic instability, telomere(definition) attrition, epigenetic alterations, chromatin remodeling defects, loss of proteostasis(definition), and impaired autophagy(definition). Additional hallmarks include mitochondrial dysfunction(definition), stem cell exhaustion, cellular senescence(definition), deregulated nutrient-sensing, altered intercellular communication, chronic inflammation, and dysbiosis. Each hallmark not only manifests with age but also accelerates aging when exacerbated, while targeted interventions can slow or even reverse their effects. Collectively, these mechanisms establish a unifying framework to explain organismal aging, its links to age-related diseases, and the therapeutic prospects of approaches which are designed to enhance longevity and health-span. This review discusses the findings on the key cellular and molecular hallmarks of senescence with a focus on telomere attrition, epigenetic alterations, mitochondrial dysfunction and stem cell exhaustion.