Interplay Between Autophagy, Cellular Senescence, and Brain Aging: Neuroprotective Implications of Intermittent Fasting

Aging is characterized by progressive deterioration in cellular function and molecular integrity, which in turn increases vulnerability to age-related diseases, such as neurodegenerative disorders. Cellular senescence is a hallmark of biological aging that plays a crucial role in the development of neurodegenerative diseases. Cellular autophagy, a lysosome-mediated process of degradation, is crucial for maintaining cellular homeostasis and longevity. Nutritional strategies, such as intermittent fasting (IF), which consist of cycles of fasting and normal feeding, have been recognized as potential methods to induce autophagy and derive health benefits. Autophagy is crucial for the degradation of sequestered proteins and damaged organelles, thus maintaining cellular vigor and balance. However, with increasing age, autophagy is compromised, suggesting the need for a stable or optimal rate of autophagy for the maintenance of cellular uptake. IF has the potential to modulate the process of autophagy by inducing changes in ATP and ADP levels during fasting through the activation of pathways such as the AMPK and Sirtuin 1 pathways, which promote the activation of autophagosome formation while simultaneously inhibiting mTOR, an inhibitor of autophagy. Despite the encouraging properties of the IF, there are constraints, as responses may vary incredibly among subjects, and the ideal duration of fasting is uncertain. Furthermore, the potential for new metabolic diseases associated with IF is not fully understood. Understanding the intricate relationships among aging, autophagy, and dietary restrictions such as intermittent fasting could pave the way for novel therapeutic strategies to increase longevity and mitigate age-related health issues. Brain aging is associated with various hallmarks leading to neurodegenerative diseases and impaired autophagy, causing the accumulation of senescent cells. Intermittent fasting, a dietary regimen, controls food intake by alternating between eating and fasting. It regulates various pathways that facilitate autophagy activation and senescent cells clearance in the brain