1 Research Group Evolutionary Physiology, Max Planck Institute for Ornithology , 82319 Seewiesen , Germany.
2 Department of Biology, University of Konstanz , D-78457 Konstanz , Germany.
Biol Lett. 2019 Mar 29;15(3):20180885. doi: 10.1098/rsbl.2018.0885.
Stress exposure can leave long-term footprints within the organism, like in telomeres (TLs), protective chromosome caps that shorten during cell replication and following exposure to stressors. Short TLs are considered to indicate lower fitness prospects, but why TLs shorten under stressful conditions is not understood. Glucocorticoid hormones (GCs) increase upon stress exposure and are thought to promote TL shortening by increasing oxidative damage. However, evidence that GCs are pro-oxidants and oxidative stress is causally linked to TL attrition is mixed . Based on new biochemical findings, we propose the metabolic telomere attrition hypothesis: during times of substantially increased energy demands, TLs are shortened as part of the transition into an organismal 'emergency state', which prioritizes immediate survival functions over processes with longer-term benefits. TL attrition during energy shortages could serve multiple roles including amplified signalling of cellular energy debt to re-direct critical resources to immediately important processes. This new view of TL shortening as a strategy to resolve major energetic trade-offs can improve our understanding of TL dynamics. We suggest that TLs are master regulators of cell homeostasis and propose future research avenues to understand the interactions between energy homeostasis, metabolic regulators and TL.
压力暴露会在生物体内留下长期的痕迹，如端粒（TLs），这是保护染色体的帽状结构，在细胞复制和暴露于应激源后会缩短。短的 TLs 被认为预示着较低的适应前景，但为什么在应激条件下 TLs 会缩短还不清楚。应激暴露会增加糖皮质激素（GCs）的水平，人们认为 GCs 通过增加氧化损伤来促进 TL 缩短。然而，GC 是促氧化剂和氧化应激与 TL 损耗有因果关系的证据是混杂的。基于新的生化发现，我们提出了代谢性端粒损耗假说：在能量需求大幅增加的时期，TL 会缩短，作为生物体进入“紧急状态”的一部分，这优先考虑了直接生存功能，而不是具有长期益处的过程。在能量短缺期间，TL 的损耗可能具有多种作用，包括放大细胞能量债务的信号，以将关键资源重新引导到立即重要的过程。这种将 TL 缩短视为解决重大能量权衡策略的新观点可以提高我们对 TL 动态的理解。我们认为 TLs 是细胞内稳态的主要调节因子，并提出了未来的研究方向，以了解能量内稳态、代谢调节剂和 TL 之间的相互作用。
