A study conducted by the University of Exeter discovered that directing tiny amounts of H2S to particular cellular areas in adult worms through the use of an H2S-releasing molecule named AP39, improved health and activity as they aged.
Future treatments to help people live healthy lives for longer could emerge from drugs that emit minute quantities of hydrogen sulfide gas (H2S), new research has indicated.
A study from the University of Exeter, funded by the US Army and charity The United Mitochondrial Disease Foundation, found that targeting tiny amounts of H2S to specific areas of cells in adult worms using a H2S-releasing molecule called AP39, greatly improved health and activity as they aged. The research, published in PNAS, concludes that targeting H2S specifically to the energy-generating machinery of cells (mitochondria) could one day be used as a healthy aging therapeutic.
The research team administered AP39 to some worms from birth, and to others after reaching adulthood. They found that this compound improved the integrity of mitochondria – the “powerhouse” of cells, which produces our cells’ energy, and kept the worms’ muscles active and moving, even well into old age, and when given mid-way through their life course.
A number of age-related conditions are linked to loss of mitochondrial function, including natural aging, neurodegenerative diseases such as Parkinson’s and Alzheimer’s as well as muscular dystrophy and primary mitochondrial diseases.
The team also found a group of proteins that regulated how genes are expressed in aging (transcription factors). Their transcription factors were found to be specifically targeted by H2S. This insight may identify new targets for therapy in aging and age-related conditions, particularly conditions affecting muscle.
Senior author Professor Tim Etheridge, of the University of Exeter, said: “Worms are a powerful genetic tool to study human health and disease and offer a strong platform to quickly identify new potential therapeutics. Diseases related to aging take a huge toll on society. Our results indicate that H2S, administered to specific parts of the cell in tiny quantities, could one day be used to help people live healthier for longer
In previous research, the team had found that they could successfully target skeletal muscle with H2S in worms, and the new paper represents the first time this technique has been applied to natural aging.
The University of Exeter has assigned the underlying technology to its spin-out MitoRx Therapeutics, which has developed next-generation compounds with much better drug characteristics as potential medicines to combat diseases of aging including neurodegenerative disorders such as Huntington’s disease as well as rare childhood conditions such as muscular dystrophy.
Co-author Professor Matt Whiteman, from the University of Exeter, said: “This study is not about extending life – it’s about living healthier lives well into older age. This could have huge benefits to society. We’re excited to see this research move to the next stages over the coming years, and hope it will one day form the basis of new treatments that we have the potential to develop with MitoRx.”
“We saw a small extension of lifespan in the worms that were targeted with H2S, and what’s unique here is that we extended healthspan – or the time they lived healthy lives. The worms still died, albeit later than normally expected, but they died very active and with young 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, 31 July 2023, Proceedings of the National Academy of Sciences.