Highly regenerative species-specific genes improve age-associated features in the adult Drosophila midgut

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 high 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. ### Competing Interest Statement The authors have declared no competing interest. * i-cell : interstitial cell HRJD : highly regenerative species-specific JmjC domain-encoding gene PH3 : phospho-histone H3 ISC : intestinal stem cell EB : enteroblast EEP : enteroendocrine progenitor EC : enterocyte EE : enteroendocrine cell DSS : dextran sulfate sodium puc : puckered Dl : Delta Jarid2 : Jumonji, AT rich interactive domain 2