Correction: A Genome-Wide Longitudinal Transcriptome Analysis of the Aging Model Podospora anserine

Abstract

Aging of biological systems is controlled by various processes which have a potential impact on gene expression. Here we report a genome-wide transcriptome analysis of the fungal aging model Podospora anserina. Total RNA of three individuals of defined age were pooled and analyzed by SuperSAGE (serial analysis of gene expression). A bioinformatics analysis identified different molecular pathways to be affected during aging. While the abundance of transcripts linked to ribosomes and to the proteasome quality control system were found to decrease during aging, those associated with autophagy increase, suggesting that autophagy may act as a compensatory quality control pathway. Transcript profiles associated with the energy metabolism including mitochondrial functions were identified to fluctuate during aging. Comparison of wildtype transcripts, which are continuously down-regulated during aging, with those down-regulated in the long-lived, copper-uptake mutant grisea, validated the relevance of age-related changes in cellular copper metabolism. Overall, we (i) present a unique age-related data set of a longitudinal study of the experimental aging model P. anserina which represents a reference resource for future investigations in a variety of organisms, (ii) suggest autophagy to be a key quality control pathway that becomes active once other pathways fail, and (iii) present testable predictions for subsequent experimental investigations.

Aging of Podospora anserina Leads to Alterations of OXPHOS and the Induction of Non-Mitochondrial Salvage Pathways

“…To reduce excessive plDNA formation, transcription of the PaCoxI gene might be downregulated. Indeed, a reduced Pa Cox1 transcript level was found in a previous transcriptome analysis [ 55 ]. Other associated factors such as RCF1 and complex IV assembly factors were elevated in old mitochondria, indicating stalled assembly ( Figure 4 B).…”

“…Both studies used different cultivation media, leading to differences in physiological aging. Borghouts and colleagues [ 100 ] analyzed much younger cultures than Philipp and colleagues [ 55 ] and those in this study. In accordance with the transcriptome data, our current complexome dataset identified an increase of the protein amount in the 18-day-old sample compared to the 6-day-old sample ( Figure 4 C).…”

“…The pronounced age-associated reorganization of the mtDNA of P. anserina, resulting in the deletion of large parts of the mtDNA, suggested that severe changes of the mitochondrial transcriptome and proteome occur during aging [ 29 , 30 , 31 , 32 , 33 ]. Subsequent studies verified this assumption [ 55 , 56 , 57 , 58 , 59 ]. For instance, the transcript and protein level of mitochondrial-encoded OXPHOS subunits such as PaCOX1 (Pa_mito_cox1), PaCOX2 (Pa_mito_cox2), and PaND4 (Pa_mito_nad4) clearly decline during aging.…”

“…An initial study analyzing PaAOX in the aged P. anserina wild type revealed that induction of alternative respiration does not occur during wild-type aging [ 100 ]. In contrast, a later genome-wide longitudinal transcriptome analysis revealed an increase of the PaAox transcript in middle-aged cultures, suggesting that the amount of AOX in aged cultures may also be increased [ 55 ]. Both studies used different cultivation media, leading to differences in physiological aging.…”

“…In the past, a number of studies focused on age-dependent changes in mitochondrial transcript and protein levels in different biological systems, including P. anserina . A longitudinal transcriptome analysis revealed that the transcript profiles associated with mitochondrial function fluctuate during the aging of P. anserina [ 55 ]. This fluctuation has also been studied on the protein level in P. anserina, but mainly with the soluble protein part of mitochondria and a focus on protein modifications [ 56 , 57 , 58 ].…”