Harnessing Hormesis: Nutritional Insights into Aging and Neurodegeneration
Mitochondria, the powerhouse of cells, produce reactive oxygen species (ROS) at moderate levels, playing a crucial role in anti-aging signaling. These ROS act as redox-active sensors maintaining mitochondrial balance and intracellular energy. However, when iron regulation fails, it leads to increased iron levels and oxidative stress, contributing to neurodegenerative diseases like Parkinson's and Alzheimer's. Central to these conditions is the dysfunction of Nrf2 signaling, a key regulator of cellular defense against oxidative stress.
Nutritional polyphenols, found in foods like fruits and vegetables, emerge as powerful regulators of the Nrf2 pathway. These compounds help restore metabolic balance, showcasing significant neuroprotective and anti-inflammatory properties. By targeting the Nrf2/vitagene pathway, these nutrients offer promising therapeutic strategies to mitigate oxidative stress and neuroinflammation, commonly linked to cognitive decline.
Exploring the connection between diet, cellular stress responses, and neurodegeneration, the study underscores the potential of hormesis—a beneficial adaptive response to mild stress. Emphasizing a holistic approach, integrating nutrition with traditional medical treatments, could pave the way for novel interventions in aging and neurodegenerative disorders, enhancing quality of life and longevity.
Article Information
Investigating hormesis, aging, and neurodegeneration: From bench to clinics
Published in Open Medicine, Vittorio Calabrese et al.
Abstract
Mitochondria-derived reactive oxygen species production at a moderate physiological level plays a fundamental role in the anti-aging signaling, due to their action as redox-active sensors for the maintenance of optimal mitochondrial balance between intracellular energy status and hormetic nutrients. Iron regulatory protein dysregulation, systematically increased iron levels, mitochondrial dysfunction, and the consequent oxidative stress are recognized to underlie the pathogenesis of multiple neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Central to their pathogenesis, Nrf2 signaling dysfunction occurs with disruption of metabolic homeostasis. We highlight the potential therapeutic importance of nutritional polyphenols as substantive regulators of the Nrf2 pathway. Here, we discuss the common mechanisms targeting the Nrf2/vitagene pathway, as novel therapeutic strategies to minimize consequences of oxidative stress and neuroinflammation, generally associated to cognitive dysfunction, and demonstrate its key neuroprotective and anti-neuroinflammatory properties, summarizing pharmacotherapeutic aspects relevant to brain pathophysiology.
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