Abstract
Author SummaryAn unequivocal demonstration that mitochondria are important for lifespan comes from studies with the nematode Caenorhabditis elegans. Mutations in mitochondrial proteins such as ISP-1 and NUO-6, which function directly in mitochondrial electron transport, lead to a dramatic increase in the lifespan of this organism. One theory proposes that toxicity of mitochondrial reactive oxygen species (ROS) is the cause of aging and predicts that the generation of the ROS superoxide should be low in these mutants. Here we have measured superoxide generation in these mutants and found that it is in fact elevated, rather than reduced. Furthermore, we found that this elevation is necessary and sufficient for longevity, as it is abolished by antioxidants and induced by mild treatment with oxidants. This suggests that superoxide can act as a signal triggering cellular changes that attenuate the effects of aging. This idea suggests a new model for the well-documented correlation between ROS and the aged phenotype. We propose that a gradual increase of molecular damage during aging triggers a concurrent, gradually intensifying, protective superoxide response.
Highlights
Mitochondrial function has been linked to the aging process in a number of ways [1]
Mitochondrial function in animals is known to decline with age [5,6], which, together with the finding that mitochondria are an important source of toxic reactive oxygen species (ROS), has led to the oxidative stress theory of aging [7,8]
This confirmed that the lifespan increase produced by the superoxide increase in mitochondrial mutants is distinct from the mechanisms that support the lifespan effects of dietary restriction [14]. hif-1 encodes a worm homologue of the vertebrate hypoxia inducible factor 1a (HIF-1a), a transcription factor involved in a number of protective mechanisms
Summary
Mitochondrial function has been linked to the aging process in a number of ways [1]. In particular, mitochondria are crucial in energy metabolism and as such have been implicated in the aging process by one of the very first theories of aging [2], the rate-ofliving theory of aging [3], which suggested that the rate of aging is proportional to the rate of energy metabolism (reviewed in [4]). Two types of mutations that affect mitochondrial function have been found to affect the rate of aging in C. elegans, mutations that shorten lifespan, such as mev-1 [9] and gas-1 [10], and mutations that lengthen lifespan, such as clk-1 [11], isp-1 [12], lrs-2 [13], and nuo-6 [14]. On the strength of the oxidative stress theory of aging it has been suggested, and supported by a number of observations (reviewed in [16,17]), that the mev-1 and gas-1 mutations reduce lifespan by increasing mitochondrial oxidative stress, and clk-1, isp-1, and nuo-6 increase lifespan by reducing it. A recent study analyzed patterns of gene expression in isp-1 mutants together with those in clk-1 and cyc-1(RNAi) [23] and
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call