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Ageing is characterized by a decline in stem cell functionality leading to dampened tissue regeneration. While the expression of microRNAs across multiple species is markedly altered with age, the mechanism by which they govern stem cell-sustained tissue regeneration is unknown. We report that in the  Drosophila  testis, the conserved  miR-9a  is expressed in germline stem cells and its levels are significantly elevated during ageing. Transcriptome and functional analyses show that  miR-9a  directly regulates the expression of the adhesion molecule N-cadherin (N-cad).  miR-9a  null mutants maintain a higher number of stem cells even in the aged tissue. Remarkably, this rise fails to improve tissue regeneration and results in reduced male fertility. Similarly, overexpression of N-cad also results in elevated stem cell number and decreased regeneration. We propose that  miR-9a  downregulates  N-cad  to enable adequate detachment of stem cells toward differentiation, thus providing the necessary directionality toward terminal differentiation and spermatogenesis.

miR-9a modulates maintenance and ageing of Drosophila germline stem cells by limiting N-cadherin expression