A peroxisome is one of the many different varieties of membrane-bound organelle found in eukaryotic cells, a feature of organisms ranging from nematode worms to flies to mice to humans. The peroxisome is involved in oxidative reactions and lipid metabolism, such as conducting beta-oxidation of fatty acids, and both manufacture and scavenging of oxidative molecules such as hydrogen peroxide. Core cell functions of this nature are well understood in isolation, but the program of mapping out how these functions change with age, how they all interact with one another, and the degree to which they are relevant to age-related dysfunction in cells, tissues, and organs, is both much more challenging and at a much more rudimentary stage.
In today's open access preprint paper, the authors note that the peroxisome is particularly understudied in the context of aging. They have demonstrated that the number of peroxisomes in cells declines systemically in early aging in nematode worms. Interfering in this process to maintain the presence of peroxisomes in cells into later life improves health and slows aging. Interestingly, it appears to do so by maintaining youthful mitochondrial structure and function. Why this is the case is an open question; clearly expression levels of mitochondrial proteins are favorably altered, but it is unclear as to what about the continued presence of peroxisomes in the cells of aged animals achieves that outcome.
Peroxisomes execute essential functions in cells, including detoxification and lipid oxidation. Despite their centrality to cell biology, the relevance of peroxisomes to aging remains understudied. We recently reported that peroxisomes are degraded en masse via pexophagy during early aging in the nematode Caenorhabditis elegans, and we found that downregulating the peroxisome-fission protein PRX-11/PEX11 prevents this age-dependent pexophagy and extends lifespan.
Here, we further investigated how prx-11 inhibition promotes longevity. Remarkably, we found that reducing peroxisome degradation with age led to concurrent improvements in another organelle: mitochondria. Animals lacking prx-11 function showed tubular, youthful mitochondria in older ages, and these enhancements required multiple factors involved in mitochondrial tubulation and biogenesis, including FZO-1/Mitofusin, UNC-43 protein kinase, and DAF-16/FOXO. Importantly, mutation of each of these factors negated lifespan extension in prx-11-defective animals, indicating that pexophagy inhibition promotes longevity only if mitochondrial health is co-maintained.
Our data supports a model in which peroxisomes and mitochondria track together with age and interdependently influence animal lifespan.
View the full article at FightAging
