0000000000347532

AUTHOR

Sebastian Brandhorst

showing 5 related works from this author

Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy

2017

Fasting reduces glucose levels and protects mice against chemotoxicity, yet drugs that promote hyperglycemia are widely used in cancer treatment. Here, we show that dexamethasone (Dexa) and rapamycin (Rapa), commonly administered to cancer patients, elevate glucose and sensitize cardiomyocytes and mice to the cancer drug doxorubicin (DXR). Such toxicity can be reversed by reducing circulating glucose levels by fasting or insulin. Furthermore, glucose injections alone reversed the fasting-dependent protection against DXR in mice, indicating that elevated glucose mediates, at least in part, the sensitizing effects of rapamycin and dexamethasone. In yeast, glucose activates protein kinase A (P…

0301 basic medicineTime FactorsImmunology and Microbiology (all)Peptide Hormonesmedicine.medical_treatmentAMP-Activated Protein KinasesToxicologyPathology and Laboratory MedicineBiochemistryDexamethasoneMiceEndocrinologyAMP-activated protein kinaseAtrial natriuretic peptideNatriuretic Peptide BrainMedicine and Health SciencesNatriuretic peptideInsulinSmall interfering RNAsBiology (General)Statistical DatabiologyOrganic CompoundsGeneral NeuroscienceMonosaccharidesHeartFastingMetformin3. Good healthMetforminNucleic acidsChemistryPhysical SciencesFemaleAnatomyGeneral Agricultural and Biological SciencesStatistics (Mathematics)Atrial Natriuretic FactorResearch Articlemedicine.drugmedicine.medical_specialtyQH301-705.5medicine.drug_classCarbohydratesEGR1Antineoplastic AgentsCardiotoxinsGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciencesNatriuretic PeptideStress PhysiologicalInternal medicineGeneticsmedicineAnimalsNon-coding RNAProtein kinase AEarly Growth Response Protein 1Diabetic EndocrinologyNeuroscience (all)Biochemistry Genetics and Molecular Biology (all)Biology and life sciencesToxicityGeneral Immunology and MicrobiologyInsulinOrganic ChemistryChemical CompoundsCorrectionAMPKCyclic AMP-Dependent Protein KinasesHormonesGene regulationDietAtrial Natriuretic PeptideMice Inbred C57BLNeuroscience (all); Immunology and Microbiology (all); Biochemistry Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all)Glucose030104 developmental biologyEndocrinologyAgricultural and Biological Sciences (all)CytoprotectionMetabolic DisordersHyperglycemiaCardiovascular Anatomybiology.proteinRNAGene expressionMathematicsPLOS Biology
researchProduct

A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan

2015

SummaryProlonged 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. 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 c…

MaleAbdominal Fat; Adult; Aged; Aging; Animals; Body Weight; Cardiovascular Diseases; Diet; Female; Humans; Male; Mice; Mice Inbred C57BL; Middle Aged; Neoplasms; Neurogenesis; Pilot Projects; Psychomotor Performance; Regeneration; Saccharomyces cerevisiae; Young Adult; Cognition; Fasting; LongevityAgingPhysiologyPilot ProjectsMiceCognitionNeoplasmsCardiovascular DiseaseSettore MED/49 - Scienze Tecniche Dietetiche Applicatemedia_common2. Zero hungerNeurogenesisLongevityFastingMiddle Aged3. Good healthCardiovascular DiseasesFemaleStem cellHumanAdultmedicine.medical_specialtyNeurogenesismedia_common.quotation_subjectLongevityAbdominal FatSaccharomyces cerevisiaeBiologyArticleYoung AdultImmune systemInternal medicineDiabetes mellitusmedicineAnimalsHumansRegenerationPilot ProjectAdverse effectCell Biology; Molecular Biology; PhysiologyMolecular BiologyAgedAnimalBody WeightCell Biologymedicine.diseaseMiddle ageDietMice Inbred C57BLEndocrinologyCancer cellNeoplasmNeurogenesiPsychomotor Performance
researchProduct

Low Protein Intake Is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population

2014

SummaryMice and humans with growth hormone receptor/IGF-1 deficiencies display major reductions in age-related diseases. Because protein restriction reduces GHR-IGF-1 activity, we examined links between protein intake and mortality. Respondents aged 50–65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer death risk during the following 18 years. These associations were either abolished or attenuated if the proteins were plant derived. Conversely, high protein intake was associated with reduced cancer and overall mortality in respondents over 65, but a 5-fold increase in diabetes mortality across all ages. Mouse studies confirmed the effect…

Malemedicine.medical_specialtyLow proteinnutrition protein intake caloric restriction nutrientsPhysiologymedicine.medical_treatmentLongevityCalorie restrictionBreast NeoplasmsGrowth hormone receptorBiologyArticleMiceLow-protein dietNeoplasmsDiabetes mellitusInternal medicineDiabetes MellitusDiet Protein-RestrictedmedicineAnimalsHumansInsulin-Like Growth Factor IMelanomaMolecular BiologyAgedProportional Hazards ModelsMice KnockoutMice Inbred BALB CIncidence (epidemiology)CancerCell BiologyMiddle Agedmedicine.diseaseMiddle ageMice Inbred C57BLCross-Sectional StudiesEndocrinologyFemaleCarrier ProteinsFollow-Up StudiesSignal TransductionCell Metabolism
researchProduct

Correction: Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy.

2017

[This corrects the article DOI: 10.1371/journal.pbio.2001951.].

General Immunology and MicrobiologyQH301-705.5General NeuroscienceBiology (General)General Agricultural and Biological SciencesGeneral Biochemistry Genetics and Molecular BiologyPLoS Biology
researchProduct

Fasting-mimicking diet prevents high-fat diet effect on cardiometabolic risk and lifespan

2021

Diet-induced obesity is a major risk factor for metabolic syndrome, diabetes and cardiovascular disease. Here, we show that a 5-d fasting-mimicking diet (FMD), administered every 4 weeks for a period of 2 years, ameliorates the detrimental changes caused by consumption of a high-fat, high-calorie diet (HFCD) in female mice. We demonstrate that monthly FMD cycles inhibit HFCD-mediated obesity by reducing the accumulation of visceral and subcutaneous fat without causing loss of lean body mass. FMD cycles increase cardiac vascularity and function and resistance to cardiotoxins, prevent HFCD-dependent hyperglycaemia, hypercholesterolaemia and hyperleptinaemia and ameliorate impaired glucose and…

medicine.medical_specialtyEndocrinology Diabetes and MetabolismLongevityDiet High-FatMiceVascularityMetabolic DiseasesPhysiology (medical)Internal medicineDiabetes mellitusKetogenesisInternal MedicineMedicineAnimalsRisk factorCardiometabolic Riskbusiness.industrySettore BIO/16 - Anatomia UmanaCell BiologyFastingmedicine.diseaseObesityEndocrinologyAgeingCardiovascular DiseasesLean body massFemaleMetabolic syndromemedicine.symptombusiness
researchProduct