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Mitochondria hormesis delays aging and associated diseases in Caenorhabditis elegans impacting on key ferroptosis players.

ABSTRACT: Excessive iron accumulation or deficiency leads to a variety of pathologies in humans and developmental arrest in the nematode Caenorhabditis elegans. Instead, sub-lethal iron depletion extends C. elegans lifespan. Hypoxia preconditioning protects against severe hypoxia-induced neuromuscular damage across species but it has low feasible application. In this study, we assessed the potential beneficial effects of genetic and chemical interventions acting via mild iron instead of oxygen depletion. We show that limiting iron availability in C. elegans through frataxin silencing or the iron chelator bipyridine, similar to hypoxia preconditioning, protects against hypoxia-, age-, and proteotoxicity-induced neuromuscular deficits. Mechanistically, our data suggest that the beneficial effects elicited by frataxin silencing are in part mediated by counteracting ferroptosis, a form of non-apoptotic cell death mediated by iron-induced lipid peroxidation. This is achieved by impacting on different key ferroptosis players and likely via gpx-independent redox systems. We thus point to ferroptosis inhibition as a novel potential strategy to promote healthy aging.

SUBMITTER: Schiavi A

PROVIDER: S-EPMC10067770 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Mitochondria hormesis delays aging and associated diseases in Caenorhabditis elegans impacting on key ferroptosis players.

Schiavi Alfonso A Salveridou Eva E Brinkmann Vanessa V Shaik Anjumara A Menzel Ralph R Kalyanasundaram Sumana S Nygård Ståle S Nilsen Hilde H Ventura Natascia N

iScience 20230321 4

Excessive iron accumulation or deficiency leads to a variety of pathologies in humans and developmental arrest in the nematode Caenorhabditis elegans. Instead, sub-lethal iron depletion extends C. elegans lifespan. Hypoxia preconditioning protects against severe hypoxia-induced neuromuscular damage across species but it has low feasible application. In this study, we assessed the potential beneficial effects of genetic and chemical interventions acting via mild iron instead of oxyg ...[more]

PMID: 37020951

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Project description:In Caenorhabditis elegans, the binding of Piwi protein to a non-coding RNA form, called piRNA, has been found to be important to both reproductive and aging processes. As the biosynthesis of piRNA is modulated by mitochondrial function, it is likely that the interaction between mitochondrial function and piRNA expression plays an unknown, yet important, role in reproductive and aging processes because both processes are known to be affected by declines in mitochondrial quality and activity. While the relationship between reproduction and longevity is not characterized in full, the optimality theory of aging and the disposable soma theory suggest that a trade-off between energy and resources is needed for reproductive and aging maintenance. In this study, the influence of mitochondrial variations, via a respiratory chain complex IV (COX1) polymorphism, on piRNA expression was examined in relation to the reproductive and aging outcomes of C. elegans. The COX1 polymorphism in mitochondria was found to affect the number of piRNAs expressed, the development of germ cells, and the length of the lifespan of the nematodes. Interestingly, more than two-thirds of the piRNA expression changes associated with the mitochondrial variation were found to also be affected by age. A gene ontology analysis of the altered piRNA species found that the piRNAs affected by mitochondrial variation and age were linked to genes known to have roles in reproductive and developmental function. Moreover, a piRNA-lncRNA-mRNA regulatory network based on the differential expression patterns of piRNA related to the mitochondrial variation was constructed to further identify potential gene targets with functional interactions. Similarly, this network identified genes involved in reproduction, development, and aging processes. These findings provide new insight into understanding how mitochondrial variations may regulate piRNA expression and may influence the underlying molecular mechanisms that affect reproduction and aging.

Dataset Information

Mitochondria hormesis delays aging and associated diseases in Caenorhabditis elegans impacting on key ferroptosis players.

Publications

Mitochondria hormesis delays aging and associated diseases in <i>Caenorhabditis elegans</i> impacting on key ferroptosis players.

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