Brain aging mechanisms are the complex cellular and molecular processes that contribute to the progressive decline in neurological structure and function over an organism’s lifespan. These mechanisms include the accumulation of oxidative stress, chronic neuroinflammation, mitochondrial dysfunction, and the gradual loss of synaptic integrity. Hormonal shifts, such as the decline in estrogen, progesterone, and testosterone, are considered significant accelerators of these age-related changes. Understanding these underlying processes is paramount for developing effective neuroprotective and longevity interventions.
Origin
The study of brain aging has roots in early neuropathology but gained significant molecular traction with the development of the Free Radical Theory of Aging in the mid-20th century. The integration of hormonal health into this domain stems from the discovery of steroid hormone receptors in the hippocampus and cortex, establishing a direct link between endocrine senescence and neurodegeneration. This field continues to evolve, focusing increasingly on the interplay between genetics, metabolism, and environmental factors.
Mechanism
Key mechanisms involve the dysregulation of energy metabolism, where neurons become resistant to glucose uptake, leading to hypometabolism. This is compounded by mitochondrial failure, which increases reactive oxygen species (ROS) production and damages cellular components. Furthermore, microglial activation drives chronic, low-grade inflammation, contributing to the pruning of functional synapses and the accumulation of protein aggregates, ultimately impairing neural network communication and cognitive output.
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