article published yes Hiroki Nagai author 608df3e6-e2ab-11ed-8890-c9318cec7da40000-0003-1671-9434 Yuya Adachi author Tenki Nakasugi author Ema Takigawa author Junichiro Ui author Takashi Makino author Masayuki Miura author Yu Ichiro Nakajima author XiFe department Background: The remarkable regenerative abilities observed in planarians and cnidarians are closely linked to the active proliferation of adult stem cells and the precise differentiation of their progeny, both of which typically deteriorate during aging in low regenerative animals. While regeneration-specific genes conserved in highly regenerative organisms may confer regenerative abilities and long-term maintenance of tissue homeostasis, it remains unclear whether introducing these regenerative genes into low regenerative animals can improve their regeneration and aging processes. Results: Here, we ectopically express highly regenerative species-specific JmjC domain-encoding genes (HRJDs) in Drosophila, a widely used low regenerative model organism. Surprisingly, HRJD expression impedes tissue regeneration in the developing wing disc but extends organismal lifespan when expressed in the intestinal stem cell lineages of the adult midgut under non-regenerative conditions. Notably, HRJDs enhance the proliferative activity of intestinal stem cells while maintaining their differentiation fidelity, ameliorating age-related decline in gut barrier functions. Conclusions: These findings together suggest that the introduction of highly regenerative species-specific genes can improve stem cell functions and promote a healthy lifespan when expressed in aging animals. https://research-explorer.ista.ac.at/download/17408/17417/2024_BMCBio_Nagai.pdf application/pdfno https://creativecommons.org/licenses/by/4.0/ Springer Nature2024 eng 1741-7007 39090637 00128289320000110.1186/s12915-024-01956-4 22 NAGAI H, Adachi Y, Nakasugi T, et al. Highly regenerative species-specific genes improve age-associated features in the adult Drosophila midgut. <i>BMC Biology</i>. 2024;22. doi:<a href="https://doi.org/10.1186/s12915-024-01956-4">10.1186/s12915-024-01956-4</a> H. NAGAI <i>et al.</i>, “Highly regenerative species-specific genes improve age-associated features in the adult Drosophila midgut,” <i>BMC Biology</i>, vol. 22. Springer Nature, 2024. NAGAI, HIROKI, et al. “Highly Regenerative Species-Specific Genes Improve Age-Associated Features in the Adult Drosophila Midgut.” <i>BMC Biology</i>, vol. 22, 157, Springer Nature, 2024, doi:<a href="https://doi.org/10.1186/s12915-024-01956-4">10.1186/s12915-024-01956-4</a>. H. NAGAI, Y. Adachi, T. Nakasugi, E. Takigawa, J. Ui, T. Makino, M. Miura, Y.I. Nakajima, BMC Biology 22 (2024). NAGAI H, Adachi Y, Nakasugi T, Takigawa E, Ui J, Makino T, Miura M, Nakajima YI. 2024. Highly regenerative species-specific genes improve age-associated features in the adult Drosophila midgut. BMC Biology. 22, 157. NAGAI, H., Adachi, Y., Nakasugi, T., Takigawa, E., Ui, J., Makino, T., … Nakajima, Y. I. (2024). Highly regenerative species-specific genes improve age-associated features in the adult Drosophila midgut. <i>BMC Biology</i>. Springer Nature. <a href="https://doi.org/10.1186/s12915-024-01956-4">https://doi.org/10.1186/s12915-024-01956-4</a> NAGAI, HIROKI, Yuya Adachi, Tenki Nakasugi, Ema Takigawa, Junichiro Ui, Takashi Makino, Masayuki Miura, and Yu Ichiro Nakajima. “Highly Regenerative Species-Specific Genes Improve Age-Associated Features in the Adult Drosophila Midgut.” <i>BMC Biology</i>. Springer Nature, 2024. <a href="https://doi.org/10.1186/s12915-024-01956-4">https://doi.org/10.1186/s12915-024-01956-4</a>. 174082024-08-11T22:01:11Z2025-09-08T08:51:29Z