From Hydra to rotifer and beyond: implications for human aging and delayed senescence

Hydra vulgaris ("Hydra") exhibits negligible senescence due to continuous self-renewal and stem cell cycling, contrasting sharply with short-lived, eutelic rotifers that exhibit rapid aging and fixed somatic cell numbers post-development. These organisms therefore represent extremes on the spectrum of invertebrate lifecycles and offer a unique opportunity to test whether patterns of gene expression associated with repressed senescence in Hydra can delay senescence in aging-prone animal models. We hypothesize that introducing Hydra-like gene expression profiles into rotifers (e.g., Brachionus manjavacas) via genetic manipulation will extend healthspan and reduce age-related mortality, providing proof-of-principle for effective manipulation of conserved anti-aging mechanisms. An iterative experimental strategy is proposed, starting with genetic manipulation of key targets in rotifers, followed by validation in Daphnia and mouse models (including strains with enhanced healing or rapid aging). Potential trade-offs, such as neoplasia risk from repressed senescence, will be monitored and mitigated. Data from this approach may identify pathways to inform strategies for delaying aging hallmarks in more complex organisms, including humans. This would assist in the development of appropriate human geroprotective strategies.