Hormesis and brain diseases.

Hormesis, the concept that low doses of potentially harmful stressors can elicit adaptive, beneficial effects, plays a significant role in brain health and aging. Neurohormesis refers to the adaptive response of neurons to mild stress, activating pathways that enhance cellular repair. As the brain ages, it experiences disruptions in energy metabolism, oxidative stress, mitochondrial dysfunction, and chronic inflammation, all of which contribute to neurodegenerative diseases like stroke, Parkinson's, Alzheimer's and multiple sclerosis (MS). However, low-dose stressors such as exercise, fasting, and certain dietary compounds have been shown to activate stress-resilience mechanisms, promoting brain health and delaying neurodegeneration. Dietary interventions, such as calorie restriction (CR) and intermittent fasting (IF), stimulate neuroprotective signaling, involving molecular targets like NF-E2-related factor 2 (NRF2), cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF). These factors regulate stress-related chaperones and promote cognitive function. The chapter highlights the role of mitochondrial health, autophagy, and circadian rhythms in aging and neurohormesis by CR and IF. Despite the potential of hormetic interventions, aging impairs the capacity of the brain to respond to stress, making it more vulnerable to neurodegeneration. Understanding neurohormesis offers promising therapeutic avenues for enhancing brain resilience and delaying the onset of age-related cognitive decline and neurodegenerative diseases. The integration of advanced technologies, such as multi-omics and epigenetic studies, could further elucidate the protective effects of hormesis on brain health, paving the way for targeted interventions to combat neurodegeneration.