Neurodegenerative Decline is the progressive and irreversible loss of structure or function of neurons, encompassing the gradual deterioration of the central and peripheral nervous systems, leading to corresponding cognitive and motor impairment. This clinical trajectory is characterized by the accumulation of misfolded proteins, chronic neuroinflammation, and oxidative stress, which collectively compromise synaptic integrity and neuronal survival. Understanding the hormonal and metabolic factors that contribute to this decline is a central focus of longevity medicine.
Origin
The term is rooted in neuropathology and geriatric medicine, describing the common pathology underlying diseases like Alzheimer’s, Parkinson’s, and Amyotrophic Lateral Sclerosis (ALS). The etymology combines ‘neuro’ (nerve) and ‘degeneration’ (deterioration), reflecting a breakdown of neural tissue. Recent endocrinology research has established a strong link between hormonal dysregulation, particularly deficits in neurosteroids like progesterone and estrogen, and the acceleration of this decline, moving the concept into the domain of hormonal health.
Mechanism
The primary mechanism involves a cascade of cellular events, beginning with mitochondrial dysfunction that impairs cellular energy production and increases reactive oxygen species. This oxidative stress, combined with chronic microglial activation, drives neuroinflammation and compromises the brain’s clearance mechanisms, leading to the aggregation of toxic protein plaques and tangles. Hormonal deficits, such as low thyroid hormone or insulin resistance, exacerbate this pathology by reducing neurotrophic factor support and impairing glucose metabolism, thus making neurons more vulnerable to excitotoxicity and apoptosis.
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