Prolonged Fasting and Health: Video Discussion with Valter Longo

Prolonged fasting (PF) promotes stress resistance, but its effects on longevity are poorly understood. We show that alternating PF and nutrient-rich medium extended yeast lifespan independently of established pro-longevity genes.

The Relationship Between Caloric Intake & Health

Dr. Valter Longo, USC Professor in Gerontology and Biological Science and Director of the USC Longevity Institute, is a prominent research figure in the field of gerontology. His research into the relationship between caloric restriction and human health has received significant academic and public interest, and has heavily impacted mainstream views on prolonged fasting and nutritional health.

Since 1997 Dr. Valter Longo has worked to uncover the complex and fascinating relationship between caloric intake and human aging, and in doing so has taken significant steps towards developing practical dietary interventions that can effectively combat the global burden of age-related disorders.

Through his ongoing efforts, the health benefits associated with various types of caloric restriction have become increasingly well-defined; recent publications by Dr. Longo have shown that periodic fasting stimulates immune protection and regeneration during chemotherapy, and decreases risk factors for various age-related disorders including diabetes, cardiovascular disease, and cancer. Additionally, Dr. Longo has shown that a low-protein diet slows the progression of Alzheimer’s in mice.

In mice, 4 days of a diet that mimics fasting (FMD), developed to minimize the burden of PF, decreased the size of multiple organs/systems, an effect followed upon re-feeding by an elevated number of progenitor and stem cells and regeneration. Bi-monthly FMD cycles started at middle age extended longevity, lowered visceral fat, reduced cancer incidence and skin lesions, rejuvenated the immune system, and retarded bone mineral density loss.

In old mice, FMD cycles promoted hippocampal neurogenesis, lowered IGF-1 levels and PKA activity, elevated NeuroD1, and improved cognitive performance. In a pilot clinical trial, three FMD cycles decreased risk factors/biomarkers for aging, diabetes, cardiovascular disease, and cancer without major adverse effects, providing support for the use of FMDs to promote health span. [1] [2] [3]

Prolonged fasting modifies brain neurochemistry and neuronal network activity in ways that optimize brain function and peripheral energy metabolism.

(Fig.II) Fasting: Molecular Mechanisms and Clinical Applications
[2013. Valter D. Longo, Mark P. Mattson. Cell Metabolism Review.]


Prolonged fasting modifies brain neurochemistry and neuronal network activity in ways that optimize brain function and peripheral energy metabolism. Four brain regions that are particularly important in adaptive responses to Intermittent Fasting (IF) include the hippocampus (cognitive processing), striatum (control of body movements), hypothalamus (Hyp, control of food intake and body temperature), and brainstem (control of cardiovascular and digestive systems). The brain communicates with all of the peripheral organs involved in energy metabolism. IF enhances parasympathetic activity (mediated by the neurotransmitter acetylcholine) in the autonomic neurons that innervate the gut, heart, and arteries, resulting in improved gut motility and reduced heart rate and blood pressure. By depleting glycogen from liver cells, fasting results in lipolysis and the generation of ketone bodies, causing a reduction in body fat. IF enhances insulin sensitivity of muscle and liver cells and reduces IGF-1 production. Levels of oxidative stress and inflammation are reduced throughout the body and brain in response to IF.


Prolonged fasting modifies brain neurochemistry and neuronal network activity in ways that optimize brain function and peripheral energy metabolism. Four brain regions that are particularly important in adaptive responses to Intermittent Fasting (IF) include the hippocampus (cognitive processing), striatum (control of body movements), hypothalamus (Hyp, control of food intake and body temperature), and brainstem (control of cardiovascular and digestive systems). The brain communicates with all of the peripheral organs involved in energy metabolism. IF enhances parasympathetic activity (mediated by the neurotransmitter acetylcholine) in the autonomic neurons that innervate the gut, heart, and arteries, resulting in improved gut motility and reduced heart rate and blood pressure. By depleting glycogen from liver cells, fasting results in lipolysis and the generation of ketone bodies, causing a reduction in body fat. IF enhances insulin sensitivity of muscle and liver cells and reduces IGF-1 production. Levels of oxidative stress and inflammation are reduced throughout the body and brain in response to IF.

In recent years the impact of Dr. Longo’s research has reached beyond academia, and has made a significant impact on mainstream dieting and health practices – Michael Moseley’s 5:2 diet, which was developed based on Dr. Longo’s research, has been the subject of numerous best-selling books in the United Kingdom.

Now, based on his own research into calorie restriction and human health, Dr. Longo has himself proposed some simple, safe, and effective dietary interventions that an individual can undertake to improve their own health.

Interventions for Better Health

These interventions have been suggested by Longo as a means of limiting the activation of biochemical pathways involved in aging and cancer, and of combatting obesity by allowing greater personal control over eating habits:

Restrict protein intake to 0.8g per kg of body weight per day

Protein restriction is known to limit the circulating levels of IGF-1, a protein hormone that functions in the activation of various biochemical pathways involved in aging and cancer. A low protein diet is therefore thought to prevent the activation of these harmful pathways.

Dr. Longo has explained that numerous studies have confirmed that a diet low in protein is “very protective” against damaging, pro-aging pathways. He claims that these studies, conducted in mice and in humans, provide a “very solid foundation” for reducing protein intake.

With regards to the safety of this dietary change, Dr. Longo has emphasized that “almost every medical association in the world says that this is safe.”

Prolonged fasting: Valter Longo | USC Longevity Institute @ USC Davis School of Gerontology [2014-11-26. Michelson Medical Research Foundation]Valter Longo stands next to incubators in his team lab located at the USC Longevity Institute, part of the USC Davis School of Gerontology. [2014-11-26] {#5419} (Credit: Michelson Medical Research Foundation)

Switch to a plant based diet

Dr. Longo claims that many individuals would experience health benefits by switching to a plant-based diet.

Longo, who is himself “pretty much a vegan”, claims that “a plant-based diet is by far the best for longevity and disease prevention.”

Numerous research, published both by Longo’s group and other groups, provides support for this claim by showing that plant-based dieting is associated with considerable, observable improvements in health in both humans and mice. [2] [4]

Stick to eating 2 meals a day

Dr. Longo claims that the most common eating pattern in the Western world – 3 meals a day with snacks in between – is actually suboptimal for human health, and is “clearly contributing” to the significant obesity problem in the United States.

“The idea that you can eat 5 or 6 times a day and control what you eat is just simply wrong,” Longo explains.

He claims that eating only 2 meals a day allows for much greater control of caloric intake, and could possibly help combat the growing problem of obesity in America; he believes that “prescriptions for meal timing and frequency” will prove to be a useful tool, and treatment plans targeting meal frequency should be “developed, validated and implemented.” [5]

Prolonged fasting diet plans

Dr. Longo worked with the Longevity Institute at the University of Southern California on the scientific development and clinical testing of specific meal plans which can be purchased that enable the “fasting mimicking diet” that he recommends. [6]

You can learn more about purchasing fasting mimicking diet plans by visiting ProLon® or L-Nutra Inc©. [7] [8]

Image Credit

  • (Featured Image) & (Fig.I) Valter Longo is an American biogerontologist and cell biologist known for his studies on the role of starvation and nutrient response genes on cellular protection aging and diseases and for proposing that longevity is regulated by similar genes and mechanisms in many eukaryotes. He is currently a professor at the USC Davis School of Gerontology with a joint appointment in the department of Biological Sciences as well as serving as the director of the USC Longevity Institute. from The Michelson Medical Research Foundation [MMRF]
  • (Fig.II) Fasting: Molecular Mechanisms and Clinical Applications from [2013. Valter D. Longo, Mark P. Mattson. Cell Metabolism Review.]

Related Fasting / Fasting Mimicking Diet Articles

Christopher Edward Jones is a biochemist and writer currently affiliated with Queen Mary University of London, where he is part of a research group focusing on the restriction factors of HIV. In the past he has worked with multiple biomedical research groups in both industry and academia. He has a research interest in the biochemical mechanisms of virus restriction and a general interest in all areas of science.

Christopher Edward Jones is a biochemist and writer currently affiliated with Queen Mary University of London, where he is part of a research group focusing on the restriction factors of HIV. In the past he has worked with multiple biomedical research groups in both industry and academia. He has a research interest in the biochemical mechanisms of virus restriction and a general interest in all areas of science.

Christopher Edward Jones is a biochemist and writer currently affiliated with Queen Mary University of London, where he is part of a research group focusing on the restriction factors of HIV. In the past he has worked with multiple biomedical research groups in both industry and academia. He has a research interest in the biochemical mechanisms of virus restriction and a general interest in all areas of science.

Christopher Edward Jones is a biochemist and writer currently affiliated with Queen Mary University of London, where he is part of a research group focusing on the restriction factors of HIV. In the past he has worked with multiple biomedical research groups in both industry and academia. He has a research interest in the biochemical mechanisms of virus restriction and a general interest in all areas of science.


The Michelson Medical Research Foundation's Groundwork blog is brought to you thanks to the generous support of Dr. Gary K. Michelson and his wife, Alya Michelson.

The Michelson Medical Research Foundation's Groundwork blog is brought to you thanks to the generous support of Dr. Gary K. Michelson and his wife, Alya Michelson.

The Michelson Medical Research Foundation's Groundwork blog is brought to you thanks to the generous support of Dr. Gary K. Michelson and his wife, Alya Michelson.

The Michelson Medical Research Foundation's Groundwork blog is brought to you thanks to the generous support of Dr. Gary K. Michelson and his wife, Alya Michelson.