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What is the molecular mechanism behind differential stress sensitization during fasting? 

Intermittent fasting
Testosterone
Sensitization
Doxorubicin
Intestinal mucosa
Best insight from top research papers

The molecular mechanism behind differential stress sensitization during fasting involves various pathways and processes. Fasting induces changes in plasma nutrient levels, glucose, and growth factors, creating a hostile environment for cancer cells, potentially maximizing their sensitization . Short-term starvation sensitizes cancer cells to oxidative stress and enhances the effectiveness of chemotherapy drugs against various tumors, promoting apoptosis and DNA damage . Additionally, a nanoliposome system loaded with 2-deoxy-D-glucose and doxorubicin selectively targets cancer cells by inhibiting glycolysis and promoting mitochondrial depolarization, while protecting normal cells from chemotherapy toxicity . Furthermore, fasting impacts immunological responses differently in males and females, with testosterone modulating stress-induced immune system changes, which are antagonized by estradiol . Overall, intermittent fasting affects pathways regulating metabolism, cell death, and inflammation, enhancing stress-induced cardiac performance .

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Papers (5)Insight
Open access•Posted Content•DOI
Multiomics Analyses Reveal Dynamic Bioenergetic Pathways and Functional Remodeling of the Heart During Intermittent Fasting
Thiruma V. Arumugam, Asfa Alli-Shaik, Elisa A. Liehn, Sharmelee Selvaraji, Luting Poh, Rajeev, Joonki Kim, Swa Hlf, Hao Dtz, Ratttanasopa C, David Y. Fann, Mayan Dc, Gavin Yong Quan Ng, Sang-Ha Baik, Karthik Mallilankaraman, Mathias Gelderblom, Grant R Drummond, Christopher G. Sobey, Brian K. Kennedy, Dong-Gyu Jo, Roshni R. Singaraja, Mark P. Mattson, Jayantha Gunaratne 
05 Mar 2021-bioRxiv
Intermittent fasting (IF) impacts cyclic GMP signaling, metabolism, cell processes, and inflammation in the heart, enhancing stress-induced cardiac performance through molecular and cellular adaptations.
Open access•Journal Article•DOI
Fasting differentially modulates the immunological system: its mechanism and sex difference.
Keiichi Hiramoto, Tamami Homma, Mika Jikumaru, Hirohisa Miyashita, Eisuke F. Sato, Masayasu Inoue 
01 Sep 2008-Journal of Clinical Biochemistry and Nutrition
9 Citations
Testosterone enhances stress-induced immune system modulation during fasting in males, while estradiol counteracts this effect. This differential response is attributed to the hormonal interplay observed in the study.
Open access•Journal Article•DOI
Fasting-induced differential stress sensitization in cancer treatment
S Di Biase, Valter D. Longo 
19 Apr 2016-Molecular and Cellular Oncology
24 Citations
Fasting reduces IGF-1 and mTOR levels, sensitizing cancer cells to stress. AMPK, REV1, and p53 pathways play key roles in differential stress sensitization, leading to cancer cell death.
Open access•Journal Article•DOI
Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell Types to Chemotherapy
Changhan Lee, Lizzia Raffaghello, Sebastian Brandhorst, Sebastian Brandhorst, Fernando M. Safdie, Giovanna Bianchi, Alejandro Martin-Montalvo, Vito Pistoia, Min Wei, Saewon Hwang, Annalisa Merlino, Laura Emionite, Rafael de Cabo, Valter D. Longo 
07 Mar 2012-Science Translational Medicine
522 Citations
Fasting induces oxidative stress via Akt and TOR-S6K pathways, promoting DNA damage and apoptosis in cancer cells, sensitizing them to chemotherapy and delaying tumor growth effectively.
Journal Article•DOI
Tumor-Specific Chemotherapy by Nanomedicine-Enabled Differential Stress Sensitization.
Bowen Yang, Yu Chen, Jianlin Shi 
08 Jun 2020-Angewandte Chemie
66 Citations
The molecular mechanism involves 2DG inhibiting cancer cell glycolysis, enhancing Dox-induced mitochondrial depolarization and apoptosis, while protecting normal cells from Dox toxicity, enabling tumor-specific chemotherapy.

Related Questions

How does metabolic switching during fasting affect overall health outcomes, including weight loss and disease risk?5 answersMetabolic switching during fasting plays a crucial role in overall health outcomes, impacting weight loss and disease risk. Fasting induces a shift in fuel utilization towards fatty acid oxidation, influencing metabolic flexibility and energy balance. This shift triggers various molecular and cellular responses that contribute to improved health outcomes, including weight loss, enhanced metabolic markers, and disease modification. Additionally, intermittent fasting (IF) has been shown to have anti-aging effects and attenuate age-related diseases through epigenetic modifications that control metabolic processes. However, the termination of fasting may lead to a loss of regulation in the epigenetic-transcriptomic axis, highlighting the importance of sustained fasting for long-term health benefits.
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What is the relation between fasting and kidney stones?4 answersFasting during Ramadan does not significantly increase the risk of kidney stones. Some studies suggest that the increased incidence of urinary stones during Ramadan may be due to factors such as high temperatures and humidity, rather than fasting itself. Patients with chronic kidney disease (CKD) and those on dialysis are considered to be at higher risk and are exempted from fasting. However, for patients with stable renal function, fasting during Ramadan does not appear to have harmful effects on renal function or graft function in kidney transplant recipients. It is important for higher-risk patients to receive counseling on safe fasting practices and to maintain proper hydration during fasting periods.
Does fasting affect Epigenetic alterations?3 answersFasting has been shown to affect epigenetic alterations. It can lead to changes in gene expression and signaling pathways, as well as affect the DNA methylation and histone modifications. The epigenetic modifications induced by fasting are tissue-specific and can vary depending on different developmental stages. Fasting can also influence the epigenetic landscape, which in turn can have consequences on physiological development and the risk of chronic metabolic diseases. Additionally, fasting has been found to influence the methylation profile of whole blood, with obesity influencing age-driven epigenetic changes. Bariatric surgery and subsequent weight loss have also been shown to alter methylation patterns, particularly in genes involved in metabolic processes. Therefore, fasting can have a significant impact on epigenetic alterations.
Does fasting during the night affect the expression of genes in the hypothalamus (POMC, CART, AGRP and NPY)?5 answersFasting during the night can affect the expression of genes in the hypothalamus involved in appetite regulation. The genes POMC, CART, AGRP, and NPY have been studied in relation to fasting. In one study, fasting for 4 days resulted in a decrease in npya1 mRNA expression in the olfactory bulb and an increase in npya2 mRNA expression in the midbrain. Another study found that fasting for 6 weeks led to an upregulation of agrp1 and npya1 mRNA expression in the hypothalamus of Atlantic salmon. Additionally, fasting in rats led to reduced cell counts in the hypothalamus and hippocampus, brain structures involved in food intake regulation, and increased feeding behavior. These findings suggest that fasting can influence the expression of genes involved in appetite regulation in the hypothalamus, potentially impacting feeding behavior.
What are the mechanisms by which fasting induces autophagy?4 answersFasting induces autophagy through various mechanisms. One mechanism is the downregulation of G protein-coupled receptor kinase 2 (GRK2) in the liver, which is facilitated by autophagy. Autophagy, rather than the proteasome, is the main mechanism responsible for fasting-induced GRK2 degradation. Another mechanism is the suppression of autophagy by brain-derived neurotrophic factor (BDNF) signaling via the tropomyosin receptor kinase B (TrkB) and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in the brain. Fasting also promotes autophagy in different brain regions, leading to synaptic remodeling and memory enhancement. Additionally, fasting and calorie restriction (CR) are potent non-genetic autophagy stimulators in various tissues and organs, promoting autophagy in response to food deprivation. These findings highlight the role of autophagy in fasting-induced cellular and metabolic adaptations.

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