Evaluating the potential of hydrogen sulfide to improve health with age and spaceflight
Publication Date
October 15, 2022
Creator
Cooke, Mike
Abstract
Ageing can be a debilitating process, reducing an organism’s ability to function and interact with its environment. With the world’s population increasing there is a pressing need to understand and augment the ageing process, allowing the elderly to remain functional for as long as possible. Ageing and its related diseases are closely associated with mitochondrial dysfunction. This thesis explored using novel hydrogen sulfide (H2S) compounds to maintain the mitochondria throughout the lifespan of C. elegans.
Firstly, mitochondrially targeted H2S was compared to H2S without targeting. The compounds were administered to juvenile worms with movement rate and survival observed, to match similar H2S experiments published. In addition to this the mitochondrial network fragmentation state and mitochondrial content was analysed. While both compounds improved lifetime movement rate, survival, and mitochondrial network state, mitochondrial targeting consistently expressed the largest elevation and was the only condition to also preserve mitochondrial content.
Secondly, both compounds were administered with delayed starting time points, starting from young adulthood, 2nd, or 4th day of adulthood. This was to simulate using the compounds as an ageing intervention rather than a lifetime supplement. Again, mitochondrial targeting showed the more pronounced benefits for lifetime movement rate, however neither compound affected survival. This shows an increase in the healthspan of the animals keeping them functional for longer.
Finally, having shown that H2S improved the ageing symptoms terrestrially, mitochondrially targeted H2S was administered to C. elegans during an accelerated ageing model using microgravity in spaceflight. The gene expression data provided evidence that untreated microgravity upregulated genes associated with energy generation, metabolism, and mitochondria. These are contributing factor to high oxidative damage and mitochondrially targeted H2S was able to downregulate many of these genes, helping to alleviate the damage. Microgravity also downregulated genes associated with calcium signalling, cell adhesion, ion transport and neural receptors. These factors contribute to motor control and other neurological declines. H2S was able to upregulate many of these genes.
Overall, this thesis highlights that mitochondrially targeted H2S maintained mitochondrial function throughout ageing and kept whole organisms functional for longer. This mitochondrial based H2S is a viable pathway to be explored and exploited for ageing therapeutics for both natural and accelerated ageing models.
Item Type
ethesis
Thesis Type
PhD
Supervisors
Subjects (LC)
Associated Schools / Departments
School of Medicine
eprints ID
69869
UoN Repository URI
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M_Cooke_Revisions.pdf
Type
Full-text
Description
Examined. Evaluating The Potential of Hydrogen Sulfide to Improve Health with Age and Spaceflight
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25.49 MB
Format
Adobe PDF
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