Lifespan Increase of Podospora anserina by Oleic Acid Is Linked to Alterations in Energy Metabolism, Membrane Trafficking and Autophagy.

Lea Schürmanns,Andrea Hamann,Heinz D Osiewacz

doi:10.3390/cells11030519

Abstract

The maintenance of cellular homeostasis over time is essential to avoid the degeneration of biological systems leading to aging and disease. Several interconnected pathways are active in this kind of quality control. One of them is autophagy, the vacuolar degradation of cellular components. The absence of the sorting nexin PaATG24 (SNX4 in other organisms) has been demonstrated to result in impairments in different types of autophagy and lead to a shortened lifespan. In addition, the growth rate and the size of vacuoles are strongly reduced. Here, we report how an oleic acid diet leads to longevity of the wild type and a PaAtg24 deletion mutant (ΔPaAtg24). The lifespan extension is linked to altered membrane trafficking, which abrogates the observed autophagy defects in ΔPaAtg24 by restoring vacuole size and the proper localization of SNARE protein PaSNC1. In addition, an oleic acid diet leads to an altered use of the mitochondrial respiratory chain: complex I and II are bypassed, leading to reduced reactive oxygen species (ROS) production. Overall, our study uncovers multiple effects of an oleic acid diet, which extends the lifespan of P. anserina and provides perspectives to explain the positive nutritional effects on human aging.

Highlights

The proper development of biological systems and the ability to adapt to changing environmental situations is strongly controlled by a complex network of molecular pathways
We reported that the deletion of PaAtg24, a gene coding for a sorting nexin, leads to a significant reduction of the growth rate and lifespan in P. anserina on standard growth medium [9]
An accumulation of peroxisomes was observed in the absence of PaATG24 in 7-day-old cultures, which increases during aging [1,9]

Summary

Introduction

The proper development of biological systems and the ability to adapt to changing environmental situations is strongly controlled by a complex network of molecular pathways. Impairments of these pathways lead to dysfunctions, disease and aging. We use the filamentous ascomycete Podospora anserina to unravel the molecular basis of organismic aging and development. Several molecular pathways have been described to play a role in the control of cellular homeostasis and aging of this well-established aging model (for a current review, see [1]). In aged P. anserina cultures, an increased number of autophagosomes is observed. The absence of the serine/threonine kinase PaATG1, which is crucial for the formation of autophagosomes, results in a lifespan that is shorter than that of the wild type [2]

Methods

Results

Conclusion