Short‐term dietary restriction and fasting precondition against ischemia reperfusion injury in mice

• Published in: Aging cell Vol. 9; no. 1; pp. 40 - 53
• Main Authors: Mitchell, James R., Verweij, Mariëlle, Brand, Karl, Van De Ven, Marieke, Goemaere, Natascha, Van Den Engel, Sandra, Chu, Timothy, Forrer, Flavio, Müller, Cristina, De Jong, Marion, Van IJcken, Wilfred, IJzermans, Jan N. M., Hoeijmakers, Jan H. J., De Bruin, Ron W. F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2010
• Subjects: Animals; Caloric Restriction; dietary restriction; Fasting; Gene Expression Regulation; Insulin - metabolism; Insulin-Like Growth Factor I - metabolism; ischemia reperfusion injury; kidney; Kidney Diseases - diet therapy; Kidney Diseases - genetics; Kidney Diseases - metabolism; Kidney Diseases - physiopathology; Kidney Function Tests; liver; Male; Mice; Mice, Inbred C57BL; Oligonucleotide Array Sequence Analysis; oxidative stress; Reperfusion Injury - diet therapy; Reperfusion Injury - genetics; Reperfusion Injury - metabolism; Reperfusion Injury - physiopathology; Signal Transduction; Survival Rate; Time Factors; Transcription, Genetic
• ISSN: 1474-9718; 1474-9726; 1474-9726
• DOI: 10.1111/j.1474-9726.2009.00532.x

Summary Dietary restriction (DR) extends lifespan and increases resistance to multiple forms of stress, including ischemia reperfusion injury to the brain and heart in rodents. While maximal effects on lifespan require long‐term restriction, the kinetics of onset of benefits against acute stress is not known. Here, we show that 2–4 weeks of 30% DR improved survival and kidney function following renal ischemia reperfusion injury in mice. Brief periods of water‐only fasting were similarly effective at protecting against ischemic damage. Significant protection occurred within 1 day, persisted for several days beyond the fasting period and extended to another organ, the liver. Protection by both short‐term DR and fasting correlated with improved insulin sensitivity, increased expression of markers of antioxidant defense and reduced expression of markers of inflammation and insulin/insulin‐like growth factor‐1 signaling. Unbiased transcriptional profiling of kidneys from mice subject to short‐term DR or fasting revealed a significant enrichment of signature genes of long‐term DR. These data demonstrate that brief periods of reduced food intake, including short‐term daily restriction and fasting, can increase resistance to ischemia reperfusion injury in rodents and suggest a rapid onset of benefits of DR in mammals.