Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China.
Clinical Center of Reproductive Medicine, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, 221000, China.
Redox Biol. 2024 Oct;76:103315. doi: 10.1016/j.redox.2024.103315. Epub 2024 Aug 15.
Testicular aging manifests as impaired spermatogenesis and morphological alterations in Drosophila. Nonetheless, the comprehensive molecular regulatory framework remains largely undisclosed. This investigation illustrates the impact of copper overload on testicular aging and underscores the interplay between copper overload and lncRNA. Copper overload triggers Cuproptosis through the mitochondrial TCA cycle, facilitating intracellular interactions with Ferroptosis, thereby governing testicular aging. Dysfunction of lncRNA:CR43306 also contributes to testicular aging in Drosophila, emphasizing the significance of lncRNA:CR43306 as a novel aging-associated lncRNA. Moreover, copper overload exacerbates spermatid differentiation defects mediated by lncRNA:CR43306 deficiency through oxidative stress, copper, and iron transport. Therapeutically, Ferrostatin-1 and Resveratrol emerge as potential remedies for addressing testicular aging. This study offers perspectives on the regulatory mechanisms involving copper overload and lncRNA:CR43306 deficiency in the context of testicular aging.
睾丸老化表现为果蝇精子发生受损和形态改变。然而，全面的分子调控框架在很大程度上仍未被揭示。本研究说明了铜过载对睾丸老化的影响，并强调了铜过载和长链非编码 RNA 之间的相互作用。铜过载通过线粒体 TCA 循环触发 Cuproptosis，促进细胞内与 Ferroptosis 的相互作用，从而控制睾丸老化。长链非编码 RNA:CR43306 的功能障碍也导致果蝇的睾丸老化，强调了长链非编码 RNA:CR43306 作为一种新型与衰老相关的长链非编码 RNA 的重要性。此外，铜过载通过氧化应激、铜和铁转运加剧了长链非编码 RNA:CR43306 缺陷介导的精母细胞分化缺陷。在治疗方面，Ferrostatin-1 和白藜芦醇作为治疗睾丸老化的潜在方法出现。本研究为睾丸老化中涉及铜过载和长链非编码 RNA:CR43306 缺陷的调控机制提供了新的视角。
