Cyclophilin D links programmed cell death and organismal aging in Podospora anserina
Wiley for Anatomical Society of Great Britain and Ireland
© 2010 The Authors Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland. Open access article
Cyclophilin D (CYPD) is a mitochondrial peptidyl prolyl-cis,trans-isomerase involved in opening of the mitochondrial permeability transition pore (mPTP). CYPD abundance increases during aging in mammalian tissues and in the aging model organism Podospora anserina. Here, we show that treatment of the P. anserina wild-type with low concentrations of the cyclophilin inhibitor cyclosporin A (CSA) extends lifespan. Transgenic strains overexpressing PaCypD are characterized by reduced stress tolerance, suffer from pronounced mitochondrial dysfunction and are characterized by accelerated aging and induction of cell death. Treatment with CSA leads to correction of mitochondrial function and lifespan to that of the wild-type. In contrast, PaCypD deletion strains are not affected by CSA within the investigated concentration range and show increased resistance against inducers of oxidative stress and cell death. Our data provide a mechanistic link between programmed cell death (PCD) and organismal aging and bear implications for the potential use of CSA to intervene into biologic aging.
The research was supported by grants of the Deutsche Forschungsgemeinschaft (Os75/12-1) and by the European Commission via the Integrated Project with the acronym MiMage; (LSHM-CT-2004-512020).
This is the final version of the article. Available from Wiley via the DOI in this record.
Vol. 9 (5), pp. 761 - 775