A Network of Pathways Controlling Cellular Homeostasis Affects the Onset of Senescence in Podospora anserina

Abstract

Research on Podospora anserina unraveled a network of molecular pathways affecting biological aging. In particular, a number of pathways active in the control of mitochondria were identified on different levels. A long-known key process active during aging of P. anserina is the age-related reorganization of the mitochondrial DNA (mtDNA). Mechanisms involved in the stabilization of the mtDNA lead to lifespan extension. Another critical issue is to balance mitochondrial levels of reactive oxygen species (ROS). This is important because ROS are essential signaling molecules, but at increased levels cause molecular damage. At a higher level of the network, mechanisms are active in the repair of damaged compounds. However, if damage passes critical limits, the corresponding pathways are overwhelmed and impaired molecules as well as those present in excess are degraded by specific enzymes or via different forms of autophagy. Subsequently, degraded units need to be replaced by novel functional ones. The corresponding processes are dependent on the availability of intact genetic information. Although a number of different pathways involved in the control of cellular homeostasis were uncovered in the past, certainly many more exist. In addition, the signaling pathways involved in the control and coordination of the underlying pathways are only initially understood. In some cases, like the induction of autophagy, ROS are active. Additionally, sensing and signaling the energetic status of the organism plays a key role. The precise mechanisms involved are elusive and remain to be elucidated.

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

“…At the cellular level, the vacuoles of the mutant are significantly smaller than those of the wild type, suggesting that vacuolar membrane trafficking is affected. Moreover, an accumulation of peroxisomes was observed in the absence of PaATG24 in 7-day-old cultures, which increases during aging [1,9]. To analyze how far these peroxisomes are functional, we determined peroxisomal activity.…”

“…We use the filamentous ascomycete Podospora anserina to unravel the molecular basis of organismic aging and development. Over the years, 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]). One of the identified pathways is autophagy.…”

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

“…One model organism with a strong mitochondrial etiology of aging is the ascomycete Podospora anserina [ 12 , 13 , 14 ]. This filamentous fungus is characterized by a limited lifespan.…”

“…This increase is concomitant with a reduction of the generation of the superoxide anion as a reactive oxygen species (ROS) [ 46 ]. Details about the role of ROS in the aging of P. anserina were discussed in a recent review [ 14 ]. A general role of ROS, which to a large extend are generated at the mitochondrial respiratory chain, and aging is evolutionary conserved from yeast to humans and is the kernel of the ‘mitochondrial free radical theory of aging’ [ 5 ].…”

“…A general role of ROS, which to a large extend are generated at the mitochondrial respiratory chain, and aging is evolutionary conserved from yeast to humans and is the kernel of the ‘mitochondrial free radical theory of aging’ [ 5 ]. Molecular impairments in respiration are known to increase oxidative stress and contribute to the aging process [ 14 , 47 , 48 ]. A detailed understanding of the structure and function of the respiratory machinery is therefore of paramount relevance for understanding biological aging.…”