Mechanisms of Fisetin in Extending Lifespan

Antioxidant Activity:

• • Fisetin reduces cellular reactive oxygen species (ROS) levels and increases resistance to oxidative stress. This reduction in oxidative damage is crucial as oxidative stress is a major contributor to aging and age-related diseases.

Senolytic Activity:

• • Fisetin selectively targets and eliminates senescent cells, which are known to contribute to aging and various age-related diseases. By reducing the burden of senescent cells, fisetin improves tissue homeostasis, reduces age-related pathology, and extends lifespan (Yousefzadeh et al., 2018).

Activation of Stress Response Pathways:

• • Fisetin activates key stress response pathways, including DAF-16 and SKN-1, which are involved in stress resistance and autophagy. These pathways play a significant role in enhancing lifespan by improving the organism’s ability to handle stress and maintain cellular function.

Anti-Inflammatory Effects:

• • Fisetin exhibits potent anti-inflammatory properties, which help mitigate chronic inflammation—a key driver of aging and age-related diseases. By reducing inflammation, fisetin contributes to a healthier and potentially longer lifespan.

Protection Against Neurodegenerative Diseases:

• • Fisetin has shown neuroprotective effects by inhibiting the degeneration of dopaminergic neurons and reducing amyloid beta-induced toxicity, which are significant in conditions like Parkinson’s and Alzheimer’s diseases. These effects contribute to maintaining cognitive function and extending lifespan.

Modulation of Metabolic Pathways:

• • Fisetin influences metabolic pathways such as the insulin/IGF-1 signaling pathway, which is known to affect longevity. It mimics the effects of dietary restriction and enhances mitochondrial function, contributing to extended lifespan.