Integrin restriction by miR-34 protects germline progenitors from cell death during aging

During aging, regenerative tissues must dynamically balance the two
opposing processes of proliferation and cell death. While many microRNAs
are differentially expressed during aging, their roles as dynamic
regulators of tissue regeneration have yet to be described. We show that
in the highly regenerative Drosophila testis, miR-34 levels are
significantly elevated during aging. miR-34 modulates germ cell death and
protects the progenitor germ cells from accelerated aging. However, miR-34
is not expressed in the progenitors themselves but rather in neighboring
cyst cells that kill the progenitors. Transcriptomics followed by
functional analysis revealed that during aging, miR-34 modifies integrin
signaling by limiting the levels of the heterodimeric integrin receptor
αPS2 and βPS subunits. In addition, we found that in cyst cells, this
heterodimer is essential for inducing phagoptosis and degradation of the
progenitor germ cells. Together, these data suggest that the miR-34 –
integrin signaling axis acts as a sensor of progenitor germ cell death to
extend progenitor functionality during aging.