Prolonged Healthy Aging Through Hydrogen Sulfide: A Promising Therapeutic Avenue

Recent scientific inquiries led by the University of Exeter indicate that pharmaceuticals discharging minimal quantities of hydrogen sulfide (H2S) may contribute to increased health and vitality in aging nematodes. By focusing the release of H2S in specific cellular regions via a molecule known as AP39, the research points to possible advancements in treatments for both healthy aging and age-associated ailments, such as neurodegenerative conditions and muscular maladies.

A study undertaken by the University of Exeter has revealed that channeling trace amounts of H2S into designated cellular regions within mature worms, utilizing an H2S-releasing molecule called AP39, resulted in enhanced health and activity levels during the aging process.

Emerging therapies that could facilitate individuals in leading healthier, longer lives may derive from pharmaceuticals that release negligible volumes of hydrogen sulfide gas (H2S), according to the latest findings.

Sponsored by the US Army and The United Mitochondrial Disease Foundation, the research conducted by the University of Exeter discovered that targeting minuscule volumes of H2S towards particular cellular compartments in mature worms through the molecule AP39 led to a significant uptick in health and activity as they aged. The study, which was published in the Proceedings of the National Academy of Sciences (PNAS), concludes that specifically targeting H2S to cellular mitochondria, the power-generating structures within cells, holds potential as a therapeutic approach for healthy aging.

AP39 was administered to two sets of worms: one group from birth and another after they reached maturity. It was observed that this molecular compound maintained the integrity of mitochondria, the cellular “powerhouses” responsible for energy production, and kept the nematodes’ muscles functional and agile, even into advanced age, and when administered during the middle of their lifespan.

Various age-related conditions, including the natural aging process, as well as neurodegenerative diseases like Parkinson’s and Alzheimer’s, muscular dystrophy, and primary mitochondrial diseases, are often correlated with a decline in mitochondrial functionality.

Furthermore, the researchers identified a collection of proteins—transcription factors—that regulate gene expression during aging. These transcription factors were specifically influenced by H2S, providing additional potential therapeutic targets, particularly for conditions that impact muscle function.

Professor Tim Etheridge, the senior author from the University of Exeter, stated, “Nematodes serve as a robust genetic tool for the study of human health and disease, offering a robust platform for swiftly identifying new potential therapeutics. Age-related diseases impose a substantial burden on society. Our data suggest that minute amounts of H2S, targeted to distinct cellular locations, could one day serve as a means to improve public health into old age.”

In earlier work, the research team had successfully directed H2S towards skeletal muscle tissue in nematodes. The current paper marks the inaugural application of this technique to natural aging.

The University of Exeter has transferred the foundational technology to its spin-off, MitoRx Therapeutics, which is in the process of developing next-generation compounds with superior pharmaceutical properties as potential treatments for age-related diseases, including neurodegenerative disorders like Huntington’s disease and specific childhood conditions such as muscular dystrophy.

Co-author Professor Matt Whiteman from the University of Exeter articulated, “This research is not aimed at extending lifespan but rather at enhancing the quality of life during aging. This could have significant societal implications. We look forward to advancing this research in subsequent phases and are optimistic that it could eventually form the basis for new treatments in collaboration with MitoRx.”

The study observed a marginal extension in lifespan for the nematodes that were treated with H2S, but more importantly, there was an extension in their ‘healthspan,’ or the duration of their healthy existence. While the nematodes did eventually die, they did so while maintaining an active and youthful physiology.

Reference: “Mitochondrial sulfide promotes life span and health span through distinct mechanisms in developing versus adult treated Caenorhabditis elegans” by Adriana Raluca Vintila, Luke Slade, Michael Cooke, Craig R. G. Willis, Roberta Torregrossa, Mizanur Rahman, Taslim Anupom, Siva A. Vanapalli, Christopher J. Gaffney, Nima Gharahdaghi, Csaba Szabo, Nathaniel J. Szewczyk, Matthew Whiteman and Timothy Etheridge, published on 31 July 2023, in the Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.2216141120.

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More about Hydrogen Sulfide in Aging Research

• Proceedings of the National Academy of Sciences (PNAS) Publication
• University of Exeter Research
• United Mitochondrial Disease Foundation
• Information on Hydrogen Sulfide
• MitoRx Therapeutics (Note: This is a hypothetical link, as the company was mentioned in the original text but may not exist)
• Overview of Neurodegenerative Diseases
• Muscular Dystrophy Association
• US Army Medical Research
• Information on Mitochondrial Function