Therapy-induced senescence is a state of cell cycle arrest that occurs as a response to various chemotherapeutic reagents, especially ones that cause DNA damage. Senescent cells display resistance to cell death and can impair the efficacy of chemotherapeutic strategies. Since lipids can exhibit pro-survival activity, it is envisioned in this article that probing the lipidome could provide insights into novel lipids that are involved in senescence. Therefore, a tissue culture model system is established and the cellular lipidomes of senescent and proliferating cells are comparatively analyzed. Out of thousands of features detected, 17 species are identified that show significant changes in senescent cells. The majority of these species (11 out of 17) are atypical sphingolipids, 1-deoxyceramides/dihydroceramides, which are produced as a result of the utilization of alanine, instead of serine during sphingolipid biosynthesis. These lipids are depleted in senescent cells. Elevating the levels of deoxyceramides by supplementing the growth medium with metabolic precursors or by directly adding deoxyceramide result in decreased senescence, suggesting that these species might play a key role in this process.

中文翻译：

---

未靶向的脂质组学突出了治疗诱导的衰老过程中脱氧神经酰胺的消耗。

治疗诱导的衰老是细胞周期停滞的一种状态，它是对各种化学治疗试剂（特别是引起DNA损伤的化学治疗试剂）的反应而发生的。衰老细胞显示出对细胞死亡的抵抗力，并可能削弱化学疗法的功效。由于脂质可以表现出促存活活性，因此本文预言了对脂质组的探测可以提供对涉及衰老的新型脂质的见解。因此，建立了组织培养模型系统，并对衰老和增殖细胞的细胞脂质组进行了比较分析。在检测到的数千种特征中，鉴定出17种物种显示出衰老细胞的显着变化。这些物种中的大多数（17种中的11种）是非典型鞘脂，1-脱氧神经酰胺/二氢神经酰胺，其是由于在鞘脂生物合成中利用丙氨酸而不是丝氨酸而产生的。这些脂质在衰老细胞中耗竭。通过向生长培养基补充代谢前体或直接添加脱氧神经酰胺来提高脱氧神经酰胺的水平，会导致衰老减少，这表明这些物种可能在此过程中起关键作用。