The article discusses the aging process and its impact on neuronal vulnerability, particularly in the context of neurodegenerative disorders. It highlights that while everyone ages, not everyone develops neurodegenerative diseases. The authors explore the factors that determine neuronal vulnerability, including cell size, location, metabolism of disease-specific proteins, and signal transduction pathways. They argue that successful neural aging is possible for most individuals, but cures for neurodegenerative disorders are unlikely in the near future. The article reviews the cellular and molecular changes that occur during normal aging, such as increased oxidative stress, perturbed energy homeostasis, and accumulation of damaged proteins and DNA. These changes are exacerbated in vulnerable neuronal populations in neurodegenerative disorders. The authors also discuss the role of genetic and environmental factors in determining whether neurons succumb to degeneration. Key mechanisms of neuronal death, such as apoptosis, excitotoxicity, calcium dysregulation, and mitochondrial perturbations, are explored. The accumulation of damaged molecules, including lipofuscin and aggregated proteins like Aβ, tau, and huntingtin, is highlighted as a significant factor in neuronal dysfunction and death. The article also examines the role of neurotrophic factors in protecting neurons and the importance of cytoskeletal disruption and inflammation in neurodegenerative disorders. Finally, it discusses therapeutic implications, emphasizing the potential of dietary interventions, exercise, and cognitive stimulation to slow the progression of neurodegenerative diseases.The article discusses the aging process and its impact on neuronal vulnerability, particularly in the context of neurodegenerative disorders. It highlights that while everyone ages, not everyone develops neurodegenerative diseases. The authors explore the factors that determine neuronal vulnerability, including cell size, location, metabolism of disease-specific proteins, and signal transduction pathways. They argue that successful neural aging is possible for most individuals, but cures for neurodegenerative disorders are unlikely in the near future. The article reviews the cellular and molecular changes that occur during normal aging, such as increased oxidative stress, perturbed energy homeostasis, and accumulation of damaged proteins and DNA. These changes are exacerbated in vulnerable neuronal populations in neurodegenerative disorders. The authors also discuss the role of genetic and environmental factors in determining whether neurons succumb to degeneration. Key mechanisms of neuronal death, such as apoptosis, excitotoxicity, calcium dysregulation, and mitochondrial perturbations, are explored. The accumulation of damaged molecules, including lipofuscin and aggregated proteins like Aβ, tau, and huntingtin, is highlighted as a significant factor in neuronal dysfunction and death. The article also examines the role of neurotrophic factors in protecting neurons and the importance of cytoskeletal disruption and inflammation in neurodegenerative disorders. Finally, it discusses therapeutic implications, emphasizing the potential of dietary interventions, exercise, and cognitive stimulation to slow the progression of neurodegenerative diseases.