Aging and neuronal vulnerability are central to the development of neurodegenerative disorders. While aging is a universal process, not all individuals develop neurodegenerative diseases. Neuronal vulnerability is influenced by factors such as cell size, location, metabolism of disease-specific proteins, and stress resistance mechanisms. Emerging evidence suggests that successful neural aging is possible for most, but cures for neurodegenerative disorders are unlikely in the near future. Aging leads to increased oxidative, metabolic, and ionic stress, resulting in the accumulation of damaged proteins, DNA, and membranes. This process is exacerbated in vulnerable neurons in neurodegenerative disorders. The relationship between aging and neurodegenerative disorders is complex, with factors such as genetic mutations, environmental influences, and cellular changes playing key roles. For example, mutations in genes like presenilin-1 and amyloid precursor protein (APP) cause early-onset Alzheimer's disease, while mutations in α-synuclein and Parkin cause Parkinson's disease. Neuronal vulnerability is determined by factors such as cell size, myelination, and the presence of specific neurotransmitter phenotypes. For instance, hippocampal neurons are vulnerable in Alzheimer's, while dopaminergic neurons are vulnerable in Parkinson's. The mechanisms underlying neuronal death include apoptosis, excitotoxicity, calcium dysregulation, and mitochondrial dysfunction. These processes are influenced by genetic and environmental factors, and their interplay determines whether neurons survive or degenerate. Dietary energy restriction (DR) has been shown to slow aging processes and protect neurons in animal models of neurodegenerative disorders. DR reduces oxidative stress, enhances BDNF production, and improves neurogenesis, potentially counteracting age-related dysfunction. Similarly, neurotrophic factors such as BDNF and GDNF play critical roles in neuronal survival and plasticity, and their decline with age may contribute to neurodegenerative diseases. Inflammation and immune responses also play a role in neurodegenerative disorders, with activated microglia and astrocytes contributing to disease progression. Therapeutic approaches targeting these processes, as well as antioxidants and anti-inflammatory agents, may help prevent or delay the onset of neurodegenerative diseases. While no treatments currently halt the progression of neurodegenerative disorders, interventions such as DR, exercise, and neurotrophic factor therapies show promise in slowing disease progression and promoting healthy brain aging.Aging and neuronal vulnerability are central to the development of neurodegenerative disorders. While aging is a universal process, not all individuals develop neurodegenerative diseases. Neuronal vulnerability is influenced by factors such as cell size, location, metabolism of disease-specific proteins, and stress resistance mechanisms. Emerging evidence suggests that successful neural aging is possible for most, but cures for neurodegenerative disorders are unlikely in the near future. Aging leads to increased oxidative, metabolic, and ionic stress, resulting in the accumulation of damaged proteins, DNA, and membranes. This process is exacerbated in vulnerable neurons in neurodegenerative disorders. The relationship between aging and neurodegenerative disorders is complex, with factors such as genetic mutations, environmental influences, and cellular changes playing key roles. For example, mutations in genes like presenilin-1 and amyloid precursor protein (APP) cause early-onset Alzheimer's disease, while mutations in α-synuclein and Parkin cause Parkinson's disease. Neuronal vulnerability is determined by factors such as cell size, myelination, and the presence of specific neurotransmitter phenotypes. For instance, hippocampal neurons are vulnerable in Alzheimer's, while dopaminergic neurons are vulnerable in Parkinson's. The mechanisms underlying neuronal death include apoptosis, excitotoxicity, calcium dysregulation, and mitochondrial dysfunction. These processes are influenced by genetic and environmental factors, and their interplay determines whether neurons survive or degenerate. Dietary energy restriction (DR) has been shown to slow aging processes and protect neurons in animal models of neurodegenerative disorders. DR reduces oxidative stress, enhances BDNF production, and improves neurogenesis, potentially counteracting age-related dysfunction. Similarly, neurotrophic factors such as BDNF and GDNF play critical roles in neuronal survival and plasticity, and their decline with age may contribute to neurodegenerative diseases. Inflammation and immune responses also play a role in neurodegenerative disorders, with activated microglia and astrocytes contributing to disease progression. Therapeutic approaches targeting these processes, as well as antioxidants and anti-inflammatory agents, may help prevent or delay the onset of neurodegenerative diseases. While no treatments currently halt the progression of neurodegenerative disorders, interventions such as DR, exercise, and neurotrophic factor therapies show promise in slowing disease progression and promoting healthy brain aging.