Manipulating mitochondrial reactive oxygen species alters survival in unexpected ways in a Drosophila Cdk5 model of neurodegeneration.

Reactive oxygen species (ROS) are associated with aging and neurodegeneration, but the significance of this association remains obscure. Here, using a Drosophila Cdk5 model of age-related neurodegeneration, we probe this relationship in the pathologically relevant tissue, the brain, by quantifying three specific mitochondrial ROS and manipulating these redox species pharmacologically. Our goal is to ask whether pathology-associated changes in redox state are detrimental for survival, whether they may be beneficial responses to pathology, or whether they are covariates of pathology that do not alter viability.

Changes in mitochondrial distribution occur at the axon initial segment in association with neurodegeneration in Drosophila.

Changes in mitochondrial distribution are a feature of numerous age-related neurodegenerative diseases. In Drosophila, reducing the activity of Cdk5 causes a neurodegenerative phenotype and is known to affect several mitochondrial properties. Therefore, we investigated whether alterations of mitochondrial distribution are involved in Cdk5-associated neurodegeneration.

MANIPULATING MITOCHONDRIAL REACTIVE OXYGEN SPECIES ALTERS SURVIVAL IN UNEXPECTED WAYS IN A MODEL OF NEURODEGENERATION.

Reactive oxygen species (ROS) are associated with aging and neurodegeneration, but the significance of this association remains obscure. Here, using a model of age-related neurodegeneration, we probe this relationship in the pathologically relevant tissue, the brain, by quantifying three specific mitochondrial ROS and manipulating these redox species pharmacologically. Our goal is to ask whether pathology-associated changes in redox state are detrimental for survival, whether they may be beneficial responses, or whether they are simply covariates of pathology that do not alter viability.

Changes in mitochondrial distribution occur at the axon initial segment in association with neurodegeneration in .

Changes in mitochondrial distribution are a feature of numerous age-related neurodegenerative diseases. In , reducing the activity of Cdk5 causes a neurodegenerative phenotype and is known to affect several mitochondrial properties. Therefore, we investigated whether alterations of mitochondrial distribution are involved in Cdk5-associated neurodegeneration.

What do we mean by "aging"? Questions and perspectives revealed by studies in Drosophila.

What is the nature of aging, and how best can we study it? Here, using a series of questions that highlight differing perspectives about the nature of aging, we ask how data from Drosophila melanogaster at the organismal, tissue, cellular, and molecular levels shed light on the complex interactions among the phenotypes associated with aging. Should aging be viewed as an individual's increasing probability of mortality over time or as a progression of physiological states? Are all age-correlated changes in physiology detrimental to vigor or are some compensatory changes that maintain vigor? Why do different age-correlated functions seem to change at different rates in a single individual as it ages? Should aging be considered as a single, integrated process across the scales of biological resolution, from organismal to molecular, or must we consider each level of biological scale as a separate, distinct entity? Viewing aging from these differing perspectives yields distinct but complementary interpretations about the properties and mechanisms of aging and may offer a path through the complexities related to understanding the nature of aging.