title: Effects of aging, antiaging calorie restriction and in vivo stimulation of autophagy on the urinary excretion of 8OHdG in male Sprague-Dawley rats.
abstract: 8-Hydroxy-2-deoxyguanosine (8OHdG) excreted into the urine is considered a marker of oxidative stress effect on DNA, and it is reported to be mainly produced by the DNA repair system. In previous works, we showed that autophagy was also involved in 8OHdG disposal through the degradation of oxidatively altered mitochondria. Here, we show that aging in Sprague-Dawley male rats is associated with a decline in the in vitro function of liver autophagy and a slight and not significant decrease in the urinary excretion of 8OHdG. In addition, we demonstrate that anti-aging caloric restriction maintains levels of both liver autophagy and urinary excretion of 8OHdG at very high levels throughout life. Finally, we show the in vivo stimulation of autophagy by the administration of an antilipolytic agent or everolimus, which rescues rats from the accumulation of 8OHdG in the liver mtDNA, also causes a dramatic increase in the urinary excretion of 8OHdG. The intensification of autophagy by the administration of the antilipolytic drugs to fasting rats faded progressively with increasing age, together with a reduced increase in 8OHdG output into the urine. It is concluded that the process of autophagy may play a major role in the disposal of 8OHdG with urine, and that the assay of 8OHdG levels in the urine before and after the stimulation of autophagy may provide a novel, non-invasive and safe procedure to monitor the in vivo functioning of the process.
authors.affiliation: Centro Interdipartimentale di Biologia e Patologia dell'Invecchiamento, Università di Pisa, Via Roma 55, 56126, Pisa, Italy. a.donati@med.unipi.it
authors.forename: Alessio
authors.initials: A
authors.lastname: Donati
authors.forename: Gabriella
authors.initials: G
authors.lastname: Cavallini
authors.forename: Ettore
authors.initials: E
authors.lastname: Bergamini
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D031204:Caloric Restriction; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D000068338:Everolimus; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000960:Hypolipidemic Agents; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000068338:Everolimus; D003849:Deoxyguanosine; D020123:Sirolimus