Evolutionarily conserved signaling pathways are crucial for adjusting growth, reproduction, and cell maintenance in response to altered environmental conditions or energy balance. However, we have an incomplete understanding of the signaling networks and mechanistic changes that coordinate physiological changes across tissues. We found that loss of the cAMP response element-binding protein (CREB) transcription factor significantly slows Caenorhabditis elegans’ reproductive decline, an early hallmark of aging in many animals. Our results indicate that CREB acts downstream of the transforming growth factor β (TGF-β) Sma/Mab pathway in the hypodermis to control reproductive aging, and that it does so by regulating a Hedgehog-related signaling factor, WRT-10. Overexpression of hypodermal wrt-10 is sufficient to delay reproductive decline and oocyte quality deterioration, potentially acting via Patched-related receptors in the germline. This TGF-β-CREB-Hedgehog signaling axis allows a key metabolic tissue to communicate with the reproductive system to regulate oocyte quality and the rate of reproductive decline.

进化上保守的信号通路对于响应变化的环境条件或能量平衡来调节生长，繁殖和细胞维持至关重要。但是，我们对协调整个组织的生理变化的信号网络和机制变化的理解还不完全。我们发现，cAMP反应元件结合蛋白（CREB）转录因子的丧失显着减缓了秀丽隐杆线虫的繁殖力下降，这是许多动物衰老的早期标志。我们的结果表明，CREB在皮下组织的转化生长因子β（TGF-β）Sma / Mab途径的下游起作用，以控制生殖衰老，并且它通过调节刺猬相关的信号传导因子WRT-10来起作用。皮下WRT-10的过表达足以延迟生殖衰退和卵母细胞质量恶化，可能通过种系中的修补相关受体起作用。该TGF-β-CREB-Hedgehog信号轴使关键的代谢组织与生殖系统进行通讯，以调节卵母细胞的质量和生殖衰退的速度。