title: Does autophagy mediate age-dependent effect of dietary restriction responses in the filamentous fungus Podospora anserina?
abstract: Autophagy is a well-conserved catabolic process, involving the degradation of a cell's own components through the lysosomal/vacuolar machinery. Autophagy is typically induced by nutrient starvation and has a role in nutrient recycling, cellular differentiation, degradation and programmed cell death. Another common response in eukaryotes is the extension of lifespan through dietary restriction (DR). We studied a link between DR and autophagy in the filamentous fungus Podospora anserina, a multicellular model organism for ageing studies and mitochondrial deterioration. While both carbon and nitrogen restriction extends lifespan in P. anserina, the size of the effect varied with the amount and type of restricted nutrient. Natural genetic variation for the DR response exists. Whereas a switch to carbon restriction up to halfway through the lifetime resulted in extreme lifespan extension for wild-type P. anserina, all autophagy-deficient strains had a shorter time window in which ageing could be delayed by DR. Under nitrogen limitation, only PaAtg1 and PaAtg8 mediate the effect of lifespan extension; the other autophagy-deficient mutants PaPspA and PaUth1 had a similar response as wild-type. Our results thus show that the ageing process impinges on the DR response and that this at least in part involves the genetic regulation of autophagy.
authors.affiliation: Laboratory of Genetics, Plant Sciences, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands CBS-KNAW Fungal Biodiversity Centre, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
authors.forename: Anne D
authors.initials: AD
authors.lastname: van Diepeningen
authors.affiliation: Laboratory of Genetics, Plant Sciences, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands Department of Ecological Sciences, Faculty of Earth and Life Sciences, Vrije Universiteit Amsterdam, Boelelaan 1085, 1081 HV Amsterdam, The Netherlands.
authors.forename: Daniël J P
authors.initials: DJ
authors.lastname: Engelmoer
authors.affiliation: Centre de Génétique Moléculaire, CNRS, UPR2167, 91198 Gif-sur-Yvette, France.
authors.forename: Carole H
authors.initials: CH
authors.lastname: Sellem
authors.affiliation: Laboratory of Genetics, Plant Sciences, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands.
authors.forename: Daphne H E W
authors.initials: DH
authors.lastname: Huberts
authors.affiliation: Laboratory of Genetics, Plant Sciences, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands.
authors.forename: S Marijke
authors.initials: SM
authors.lastname: Slakhorst
authors.affiliation: Centre de Génétique Moléculaire, CNRS, UPR2167, 91198 Gif-sur-Yvette, France Université Paris-Sud, 91405 Orsay, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Sainsard-Chanet
authors.affiliation: Laboratory of Genetics, Plant Sciences, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands bas.zwaan@wur.nl.
authors.forename: Bas J
authors.initials: BJ
authors.lastname: Zwaan
authors.affiliation: Laboratory of Genetics, Plant Sciences, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands.
authors.forename: Rolf F
authors.initials: RF
authors.lastname: Hoekstra
authors.affiliation: Laboratory of Genetics, Plant Sciences, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands.
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: Debets
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D002244:Carbon / Q000378:metabolism; D005508:Food Deprivation / Q000502:physiology*; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000502:physiology; D009584:Nitrogen / Q000378:metabolism; D048468:Podospora / Q000235:genetics / Q000378:metabolism*
chemical_list: D002244:Carbon; D009584:Nitrogen
keywords: Podospora anserina; ageing; autophagy; carbon and nitrogen restriction; dietary restriction; lifespan extension