Metabolism and aging in the filamentous fungus Podospora anserina

In Podospora anserina, lifespan is under the control of environmental and g enetic factors. Both suggest an important impact of metabolism on lifespan and aging. Environmental changes of temperature, of the carbon source in th e growth medium, or the addition of specific inhibitors to the growth mediu m are some of the investigated factors. Genetic approaches underscore the s ignificance of metabolism. In particular, the mitochondrial electron transp ort plays a major role. As a by-product of a cytochrome oxidase (COX) depen dent energy transduction, reactive oxygen species (ROS) are generated and l ead to damage of cellular biomolecules. Damaged mitochondria, compromised a t complex IV (COX) of the respiratory chain, signal to the nucleus and indu ce a nuclear gene, PaAox, encoding an alternative oxidase (AOX). This pathw ay resembles the retrograde response that, at least in yeast, is induced by dysfunctional mitochondria. ROS generation is lowered when electrons are t ransferred via an alternative pathway utilizing the AOX. As a consequence, lifespan of the corresponding strains is increased. Cellular copper levels were found to play a significant role not only in the generation of ROS but also have an impact on the cytoplasmic and the mitochondrial superoxide di smutase (SOD). In addition, copper is involved in the control of mitochondr ial DNA rearrangements and affects the ability of the system to remodel dam aged mitochondria. All these different components and pathways are part of the complex molecular network involved in lifespan control of this aging mo del. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.