Inhibiting the peroxisomal protein PRX-11 may preserve mitochondrial health and extended lifespan in aging Caenorhabditis elegans.
Researchers investigated how inhibiting PRX-11 could influence aging using RNA interference and a genetic loss-of-function mutation in C elegans. They assessed lifespan alongside mitochondrial morphology, mitochondrial calcium accumulation, oxidative stress, energy status, lipid storage, locomotor function, and markers of peroxisome degradation. The researchers also examined whether genes involved in mitochondrial fusion and longevity signaling mediated the effects of PRX-11 inhibition.
Compared with controls, C elegans lacking PRX-11 function retained tubular mitochondrial networks that resembled those of younger animals during later life. PRX-11 inhibition also reduced mitochondrial calcium accumulation, decreased oxidative stress, increased ATP-to-ADP ratios, enhanced lipid stores, and improved locomotor activity, findings consistent with the preservation of mitochondrial function during aging.
Longevity benefit accompanied the cellular changes. Across independent lifespan experiments, the mean lifespan increased from approximately 18 days in control animals to about 20 to 21 days following PRX-11 inhibition. Conversely, disrupting mitochondrial maintenance pathways eliminated this survival advantage. Mutations affecting FZO-1, UNC-43, or DAF-16 prevented PRX-11 inhibition from extending lifespan, indicating that preserved mitochondrial health was required for the observed longevity effect.
The researchers also found evidence of reciprocal communication between peroxisomes and mitochondria. C elegans with impaired mitochondrial maintenance exhibited accelerated peroxisome degradation early in adulthood, whereas inhibiting PRX-11 suppressed this effect, suggesting that dysfunction in either organelle may contribute to deterioration of the other during aging.
The study was limited by its experimental design in C elegans. Although the findings identified a potential mechanism linking peroxisome maintenance and mitochondrial health, the results may not translate directly to mammals or humans. In addition, the molecular signals coordinating communication between peroxisomes and mitochondria remained incompletely understood.
The findings suggested that maintaining peroxisomes during aging may help sustain mitochondrial function and promote longevity through coordinated communication between the two organelles. The study supported further investigation of organelle crosstalk as a potential target for aging research.
“Our findings identify peroxisome degradation as a modifiable event that controls mitochondrial aging,” wrote lead study author Yash Flora, of the Department of Biological Sciences at Louisiana State University, and colleagues.
The study authors reported no conflicts of interest.
Source: Aging
