Fasting Against Cancer: Valter Longo’s Breakthrough Research

Researchers at the University of Southern California has discovered that fasting may be able to limit the damaging effects of chemotherapy on the immune system.

Researchers at the University of Southern California have discovered that fasting may be able to limit the damaging effects of chemotherapy on the immune system. The claim has been made after Phase 1 Human trials, and also trials in mice, showed that cyclical fasting is capable of triggering the replacement of a damaged immune system by encouraging stem-cell based regeneration of white blood cells.

The study shows that cyclical fasting – meaning repeatedly fasting for 2 – 4 day periods over 6 months – “flipped a regenerative switch” in laboratory mice, causing haematopoietic stem cells to differentiate into cells of the immune system, generating a new population of immune cells.

Feeding vs. Fasting

Immune system defects are at the center of aging and a range of diseases. Here, we show that prolonged fasting reduces circulating IGF-1 levels and PKA activity in various cell populations, leading to signal transduction changes in long-term hematopoietic stem cells (LT-HSCs) and niche cells that promote stress resistance, self-renewal, and lineage-balanced regeneration.

Multiple cycles of fasting abated the immunosuppression and mortality caused by chemotherapy and reversed age-dependent myeloid-bias in mice, in agreement with preliminary data on the protection of lymphocytes from chemotoxicity in fasting patients. The proregenerative effects of fasting on stem cells were recapitulated by deficiencies in either IGF-1 or PKA and blunted by exogenous IGF-1.

These findings link the reduced levels of IGF-1 caused by fasting to PKA signaling and establish their crucial role in regulating hematopoietic stem cell protection, self-renewal, and regeneration.

Feeding vs. Fasting

Immune system defects are at the center of aging and a range of diseases. Here, we show that prolonged fasting reduces circulating IGF-1 levels and PKA activity in various cell populations, leading to signal transduction changes in long-term hematopoietic stem cells (LT-HSCs) and niche cells that promote stress resistance, self-renewal, and lineage-balanced regeneration.

Multiple cycles of fasting abated the immunosuppression and mortality caused by chemotherapy and reversed age-dependent myeloid-bias in mice, in agreement with preliminary data on the protection of lymphocytes from chemotoxicity in fasting patients. The proregenerative effects of fasting on stem cells were recapitulated by deficiencies in either IGF-1 or PKA and blunted by exogenous IGF-1.

These findings link the reduced levels of IGF-1 caused by fasting to PKA signaling and establish their crucial role in regulating hematopoietic stem cell protection, self-renewal, and regeneration.

Feeding vs. Fasting

Immune system defects are at the center of aging and a range of diseases. Here, we show that prolonged fasting reduces circulating IGF-1 levels and PKA activity in various cell populations, leading to signal transduction changes in long-term hematopoietic stem cells (LT-HSCs) and niche cells that promote stress resistance, self-renewal, and lineage-balanced regeneration.

Multiple cycles of fasting abated the immunosuppression and mortality caused by chemotherapy and reversed age-dependent myeloid-bias in mice, in agreement with preliminary data on the protection of lymphocytes from chemotoxicity in fasting patients. The proregenerative effects of fasting on stem cells were recapitulated by deficiencies in either IGF-1 or PKA and blunted by exogenous IGF-1.

These findings link the reduced levels of IGF-1 caused by fasting to PKA signaling and establish their crucial role in regulating hematopoietic stem cell protection, self-renewal, and regeneration.

Feeding vs. Fasting

Immune system defects are at the center of aging and a range of diseases. Here, we show that prolonged fasting reduces circulating IGF-1 levels and PKA activity in various cell populations, leading to signal transduction changes in long-term hematopoietic stem cells (LT-HSCs) and niche cells that promote stress resistance, self-renewal, and lineage-balanced regeneration.

Multiple cycles of fasting abated the immunosuppression and mortality caused by chemotherapy and reversed age-dependent myeloid-bias in mice, in agreement with preliminary data on the protection of lymphocytes from chemotoxicity in fasting patients. The proregenerative effects of fasting on stem cells were recapitulated by deficiencies in either IGF-1 or PKA and blunted by exogenous IGF-1.

These findings link the reduced levels of IGF-1 caused by fasting to PKA signaling and establish their crucial role in regulating hematopoietic stem cell protection, self-renewal, and regeneration.

As well as exerting this pro-regenerative effect, fasting was shown to protect the immune system from the toxic effects of chemotherapy; in a study observing patients who fasted for 72 hours prior to undergoing chemotherapy, fasting was found to protect haematopoietic stem cells from chemotoxicity.

Tanya Dorff, co-author of the recent USC study, suggests that by these actions cyclical fasting “may mitigate some of the harmful effects of chemotherapy.”

Chemotherapy is unarguably an efficacious cancer treatment, however it is typically associated with “significant collateral damage to the immune system”. Patients who are undergoing, or have recently undergone, chemotherapy normally have a reduced white blood cell count, and as a direct result have an increased susceptibility to infection. In such populations infection is a “major cause of mortality and morbidity.” (1)

Fasting Specifics

Fasting – which is defined as “eating no food and drinking only water for a period of days” – exerts the observed pro-regenerative effect by both encouraging the destruction of old, damaged immune cells and promoting the stem-cell based generation of new immune cells, resulting in the construction of a new, undamaged immune system. Valter Longo, corresponding author of the study, summarises the process as follows:

“When you starve, the system tries to save energy, and one of the things it can do to save energy is to recycle a lot of the immune cells that are not needed, especially those that may be damaged … Then when you re-feed, the blood cells come back.”

Longo further explains that by influencing cell signalling pathways, this lowering of white blood cell counts directly encourages haematopoietic stem cells to differentiate and proliferate into a new population of immune cells. Longo claims that the enzyme PKA and cell signalling protein IGF-1 are both involved in the process.

Summary of the major signaling pathways used by cells to regulate cellular processes.

Cells have a number of signaling systems that are capable of responding either to external stimuli or to internal stimuli. In the case of the former, external stimuli acting on cell-surface receptors are coupled to transducers to relay information into the cell using a number of different signalling pathways (Pathways 1–17). Internal stimuli derived from the endoplasmic reticulum (ER) or from metabolism activate signaling pathways independently of external signals (Pathways 18 and 19). All of these pathways generate an internal messenger that then acts through an internal sensor to stimulate the effectors that bring about different cellular responses. As described in the text, the names of these signaling pathways usually reflect a major component(s) of the pathway.

Summary of the major signaling pathways used by cells to regulate cellular processes.

Cells have a number of signaling systems that are capable of responding either to external stimuli or to internal stimuli. In the case of the former, external stimuli acting on cell-surface receptors are coupled to transducers to relay information into the cell using a number of different signalling pathways (Pathways 1–17). Internal stimuli derived from the endoplasmic reticulum (ER) or from metabolism activate signaling pathways independently of external signals (Pathways 18 and 19). All of these pathways generate an internal messenger that then acts through an internal sensor to stimulate the effectors that bring about different cellular responses. As described in the text, the names of these signaling pathways usually reflect a major component(s) of the pathway.

Summary of the major signaling pathways used by cells to regulate cellular processes.

Cells have a number of signaling systems that are capable of responding either to external stimuli or to internal stimuli. In the case of the former, external stimuli acting on cell-surface receptors are coupled to transducers to relay information into the cell using a number of different signalling pathways (Pathways 1–17). Internal stimuli derived from the endoplasmic reticulum (ER) or from metabolism activate signaling pathways independently of external signals (Pathways 18 and 19). All of these pathways generate an internal messenger that then acts through an internal sensor to stimulate the effectors that bring about different cellular responses. As described in the text, the names of these signaling pathways usually reflect a major component(s) of the pathway.

Summary of the major signaling pathways used by cells to regulate cellular processes.

Cells have a number of signaling systems that are capable of responding either to external stimuli or to internal stimuli. In the case of the former, external stimuli acting on cell-surface receptors are coupled to transducers to relay information into the cell using a number of different signalling pathways (Pathways 1–17). Internal stimuli derived from the endoplasmic reticulum (ER) or from metabolism activate signaling pathways independently of external signals (Pathways 18 and 19). All of these pathways generate an internal messenger that then acts through an internal sensor to stimulate the effectors that bring about different cellular responses. As described in the text, the names of these signaling pathways usually reflect a major component(s) of the pathway.

By encouraging the destruction of the old, damaged population of immune cells, fasting lowers the circulating levels of PKA and IGF-1. Low circulating levels of both PKA and IGF-1 are associated with increased haematopoietic stem cell production, so by reducing the levels of both, fasting exerts a large pro-regenerative effect on the immune system. It is by this process that fasting allows the generation of a new, undamaged population of immune cells. Longo notes that PKA is particularly important in this process, describing it as “the key gene that needs to shut down in order for these stem cells to switch into regenerative mode.”

Longo has emphasised that the observed effects of fasting on stem-cell based regeneration are “remarkable”, stating “if you start with a system heavily damaged by chemotherapy or aging, fasting cycles can generate, literally, a new immune system.” This reinforces hopes that fasting will be approved as a means of controlling, or reverting, the immune damage observed in chemotherapy patients.

However, despite these very suggestive findings, Dorff acknowledges that “more research is needed” and advises individuals who are undergoing, or have undergone, chemotherapy and are considering fasting that “any such dietary intervention should be undertaken only under the guidance of a physician.” Individuals who do fast should do so safely, by keeping well hydrated and being aware of the potential short-term negative effects of fasting, which include headaches, dizziness, fatigue, and low blood pressure.

Dr. Gary K. Michelson

“It is a remarkable medical research finding that the mere act of fasting short term prior to receiving a round of chemotherapy can significantly mitigate the unwanted side effects usually associated with that chemotherapy. It is wholly within the control of the patient at a time when many people are feeling helpless in the face of cancer. While the mechanism of action for the observed phenomena has not been fully delineated it is clear that the body has heretofore unrecognized adaptive processes that can, with more knowledge be recruited to benefit each of us in the fight against disease.”

Dr. Gary K. Michelson

Dr. Gary K. Michelson

“It is a remarkable medical research finding that the mere act of fasting short term prior to receiving a round of chemotherapy can significantly mitigate the unwanted side effects usually associated with that chemotherapy. It is wholly within the control of the patient at a time when many people are feeling helpless in the face of cancer. While the mechanism of action for the observed phenomena has not been fully delineated it is clear that the body has heretofore unrecognized adaptive processes that can, with more knowledge be recruited to benefit each of us in the fight against disease.”

Dr. Gary K. Michelson

Dr. Gary K. Michelson

“It is a remarkable medical research finding that the mere act of fasting short term prior to receiving a round of chemotherapy can significantly mitigate the unwanted side effects usually associated with that chemotherapy. It is wholly within the control of the patient at a time when many people are feeling helpless in the face of cancer. While the mechanism of action for the observed phenomena has not been fully delineated it is clear that the body has heretofore unrecognized adaptive processes that can, with more knowledge be recruited to benefit each of us in the fight against disease.”

Dr. Gary K. Michelson

Dr. Gary K. Michelson

“It is a remarkable medical research finding that the mere act of fasting short term prior to receiving a round of chemotherapy can significantly mitigate the unwanted side effects usually associated with that chemotherapy. It is wholly within the control of the patient at a time when many people are feeling helpless in the face of cancer. While the mechanism of action for the observed phenomena has not been fully delineated it is clear that the body has heretofore unrecognized adaptive processes that can, with more knowledge be recruited to benefit each of us in the fight against disease.”

Dr. Gary K. Michelson

Dr. Valter Longo – Longevity and Cancer
[2014-09-24; Institute of Molecular Oncology, Italy] [YouTube]

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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.