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.

中文翻译：

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miR-34对整合素的限制可保护种系祖细胞在衰老过程中免于细胞死亡

在衰老过程中，再生组织必须动态平衡增殖和细胞死亡这两个相反的过程。虽然许多 microRNA 在衰老过程中表达差异，但它们作为组织再生动态调节因子的作用尚未得到描述。我们表明，在高度再生的情况下果蝇睾丸，miR-34衰老过程中其水平显着升高。miR-34调节生殖细胞死亡并保护祖生殖细胞免于加速衰老。然而，miR-34不在祖细胞本身中表达，而是在杀死祖细胞的邻近囊细胞中表达。转录组学和功能分析表明，在衰老过程中，miR-34通过限制异二聚体整合素受体 αPS2 和 βPS 亚基的水平来修饰整合素信号传导。此外，我们发现在囊肿细胞中，这种异二聚体对于诱导祖生殖细胞的吞噬作用和降解至关重要。这些数据共同表明miR-34-整合素信号轴充当祖细胞死亡的传感器，以在衰老过程中延长祖细胞功能。