Fasting: Molecular Mechanisms and Clinical Applications

Fasting: Molecular Mechanisms and Clinical Applications

2014 February 4 | Valter D. Longo and Mark P. Mattson
Fasting, a practice with ancient roots, has been shown to have significant molecular and clinical benefits. It reduces oxidative damage and inflammation, optimizes energy metabolism, and enhances cellular protection. In lower eukaryotes, chronic fasting extends longevity by reprogramming metabolic and stress resistance pathways. In rodents, intermittent or periodic fasting protects against diabetes, cancers, heart disease, and neurodegeneration, while in humans, it helps reduce obesity, hypertension, asthma, and rheumatoid arthritis. Fasting can delay aging and help prevent and treat diseases while minimizing side effects from chronic dietary interventions. Fasting is distinct from caloric restriction (CR), which reduces daily caloric intake by 20–40% without changing meal frequency. Starvation, a chronic nutritional insufficiency, is often used as a substitute for fasting, particularly in lower eukaryotes. Fasting results in ketogenesis, promotes metabolic changes, and has medical applications, such as reducing seizures and ameliorating rheumatoid arthritis. In simple organisms like E. coli and yeast, fasting extends lifespan and enhances stress resistance. In nematodes, food deprivation increases lifespan, requiring AMPK and DAF-16. In flies, intermittent food deprivation does not affect lifespan, but food reduction extends longevity. These results indicate that fasting can have pro-longevity effects in various organisms. In mammals, fasting triggers metabolic adaptations, including ketone body production and energy source shifts. The brain benefits from fasting, with enhanced synaptic plasticity and neurogenesis. Brain-derived neurotrophic factor (BDNF) plays a key role in fasting-induced cognitive benefits. Fasting can reduce inflammation and improve metabolic syndrome by enhancing insulin sensitivity, reducing body fat, and improving cardiovascular function. It also has potential in cancer prevention and treatment by reducing IGF-1, insulin, and glucose levels, and increasing IGFBP1 and ketone bodies. Fasting has been shown to improve cognitive function and reduce neurodegeneration in animal models. It enhances neurotrophic factor signaling, reduces inflammation, and promotes neurogenesis. However, fasting may be detrimental in older individuals who begin to lose weight before death. Fasting can also reduce hypertension by lowering blood pressure and improving vascular function. It has been effective in treating rheumatoid arthritis and other conditions by reducing inflammation and oxidative stress. In humans, fasting can improve metabolic health, reduce chronic disease risk, and enhance cognitive function. However, long-term fasting may have adverse effects, and its efficacy varies among individuals. Fasting regimens should be carefully monitored, especially in vulnerable populations. Overall, fasting has significant potential to promote health and prevent disease, but its application requires careful consideration of individual needs and medical supervision. Future research should focus on understanding the molecular mechanisms of fasting and developing effective, safe, and sustainable fasting strategies for various populations.Fasting, a practice with ancient roots, has been shown to have significant molecular and clinical benefits. It reduces oxidative damage and inflammation, optimizes energy metabolism, and enhances cellular protection. In lower eukaryotes, chronic fasting extends longevity by reprogramming metabolic and stress resistance pathways. In rodents, intermittent or periodic fasting protects against diabetes, cancers, heart disease, and neurodegeneration, while in humans, it helps reduce obesity, hypertension, asthma, and rheumatoid arthritis. Fasting can delay aging and help prevent and treat diseases while minimizing side effects from chronic dietary interventions. Fasting is distinct from caloric restriction (CR), which reduces daily caloric intake by 20–40% without changing meal frequency. Starvation, a chronic nutritional insufficiency, is often used as a substitute for fasting, particularly in lower eukaryotes. Fasting results in ketogenesis, promotes metabolic changes, and has medical applications, such as reducing seizures and ameliorating rheumatoid arthritis. In simple organisms like E. coli and yeast, fasting extends lifespan and enhances stress resistance. In nematodes, food deprivation increases lifespan, requiring AMPK and DAF-16. In flies, intermittent food deprivation does not affect lifespan, but food reduction extends longevity. These results indicate that fasting can have pro-longevity effects in various organisms. In mammals, fasting triggers metabolic adaptations, including ketone body production and energy source shifts. The brain benefits from fasting, with enhanced synaptic plasticity and neurogenesis. Brain-derived neurotrophic factor (BDNF) plays a key role in fasting-induced cognitive benefits. Fasting can reduce inflammation and improve metabolic syndrome by enhancing insulin sensitivity, reducing body fat, and improving cardiovascular function. It also has potential in cancer prevention and treatment by reducing IGF-1, insulin, and glucose levels, and increasing IGFBP1 and ketone bodies. Fasting has been shown to improve cognitive function and reduce neurodegeneration in animal models. It enhances neurotrophic factor signaling, reduces inflammation, and promotes neurogenesis. However, fasting may be detrimental in older individuals who begin to lose weight before death. Fasting can also reduce hypertension by lowering blood pressure and improving vascular function. It has been effective in treating rheumatoid arthritis and other conditions by reducing inflammation and oxidative stress. In humans, fasting can improve metabolic health, reduce chronic disease risk, and enhance cognitive function. However, long-term fasting may have adverse effects, and its efficacy varies among individuals. Fasting regimens should be carefully monitored, especially in vulnerable populations. Overall, fasting has significant potential to promote health and prevent disease, but its application requires careful consideration of individual needs and medical supervision. Future research should focus on understanding the molecular mechanisms of fasting and developing effective, safe, and sustainable fasting strategies for various populations.
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Understanding Fasting%3A molecular mechanisms and clinical applications.