Summary: Researchers transferred regeneration-associated genes from simple, highly regenerative animals into fruit flies, improving intestinal stem cell function and reducing age-related intestinal decline. The findings point to new avenues for stem cell rejuvenation and anti-aging strategies.
This study indicates that genes unique to animals capable of whole-body regeneration can influence tissue maintenance and longevity-related processes in more complex species. While the work stops short of enabling full tissue regeneration in insects, it reveals measurable benefits to intestinal health and lifespan in Drosophila melanogaster.
Key Facts:
- Regeneration-associated genes from simple animals improved intestinal stem cell activity in fruit flies.
- The introduced genes reduced mis-differentiation of intestinal cells that emerges with age.
- Modified flies showed changes in lifespan, suggesting potential anti-aging applications and directions for stem cell-based therapies.
Source: University of Tokyo
Study overview: A team led by researchers at the University of Tokyo’s Graduate School of Pharmaceutical Sciences introduced a group of genes, called highly regenerative species-specific JmjC domain-encoding genes (HRJDs), from animals with robust regenerative abilities into the common fruit fly, Drosophila melanogaster. These donor species include organisms such as certain flatworms and jellyfish that can regenerate whole body parts.
The researchers hypothesized that reintroducing regeneration-associated genes lost during evolution could restore or enhance regenerative processes and stem cell functions in species with limited regenerative capacity. Instead of whole-body regeneration, the most prominent outcome was improved intestinal stem cell behavior and reduced age-associated cell mis-differentiation in the fly gut.
Associate Professor Yuichiro Nakajima explained that animals with high regenerative capacity often carry genes that maintain long-term stem cell function. Mammals and many insects lack these genes, likely due to evolutionary loss. By focusing on HRJDs, the team tested whether these genes could alter regeneration- and aging-related pathways when expressed in a low-regeneration animal like Drosophila.
Although the modified flies did not regain the ability to regenerate entire tissues, Hiroki Nagai and colleagues observed unexpected and promising changes in intestinal physiology. HRJD expression stimulated intestinal stem cell proliferation while simultaneously reducing the emergence of mis-differentiated intestinal cells that typically accumulate in aged flies. This dual effect contrasts with some interventions—such as broad antibiotic treatments—that can reduce mis-differentiation but also suppress stem cell proliferation, potentially harming tissue maintenance.
The net result of HRJD expression was a measurable impact on fly lifespan, suggesting that specific regeneration-associated genes can influence aging-related tissue decline. Because intestinal stem cell dynamics are conserved across many animals, these findings provide a useful model for exploring molecular mechanisms that could one day inform stem cell-based therapies for age-related decline in humans.
The project faced practical constraints: even short-lived model organisms like fruit flies require weeks to develop age-related phenotypes, extending experimental timelines. Despite these challenges, the team has produced a genetically modified Drosophila resource that can be used to dissect HRJD function in greater detail.
Key questions remain. The precise molecular mechanisms by which HRJDs influence stem cell division and differentiation are not yet resolved. It is unclear whether HRJDs act alone or in concert with other factors from regenerative species. Further work will aim to map the pathways engaged by HRJDs and to test whether similar approaches can be adapted to other tissues or organisms.
Nakajima emphasized that this study marks an early but important step: “Our modified flies offer a valuable system to uncover unprecedented mechanisms of stem cell rejuvenation. Given that human intestinal stem cell activity declines with age, understanding these pathways could suggest new therapeutic strategies.”
Funding: This work was supported by JSPS/MEXT KAKENHI (grant numbers JP22J01430 to H.N., JP21H04774, JP23H04766, JP24H00567 to M.M., and JP17H06332, JP22H02762, JP23K18134, JP23H04696 to Y.N.), AMED-Aging (JP21gm5010001 to M.M.), AMED-PRIME (JP22gm6110025 to Y.N.), and the Sadako O. Hirai Ban Award for Young Researchers (H.N.).
About this aging and genetics research news
Author: Rohan Mehra
Source: University of Tokyo
Contact: Rohan Mehra – University of Tokyo
Image: The image is credited to Neuroscience News
Original Research: The findings will appear in BMC Biology.