Kern Carina, Bonventre Joseph V, Justin Alexander W, Kashani Kianoush, Reynolds Elizabeth, Siew Keith, Davis Bill, Karakoy Halime, Grzesiak Nikodem, Bailey Damian Miles
LinkGevity, Babraham Research Campus, Cambridge, UK.
Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Oncogene. 2025 May 29. doi: 10.1038/s41388-025-03431-y.
Necrosis is uncontrolled cell death that marks the irreversible threshold of biological degeneration. Rooted in the Greek nekros (death), it is a pivotal mechanism underlying numerous diseases, including cancer, as well as renal, cardiac, neuronal, and hepatic disorders, and more broadly, the aging process. Despite its profound impact on morbidity and mortality, necrosis remains untreatable and has long been viewed as a chaotic, unavoidable aspect of biology. This review examines the mechanisms of necrosis and outlines its far-reaching impact on health, as revealed by emerging evidence. Furthermore, we explore its potential as a game-changing therapeutic target. Inhibiting necrosis could revolutionize treatments for acute and chronic age-related conditions like cancer, kidney disease, cardiovascular disease (including heart attacks and strokes), and neurodegeneration, while also preserving resilience-and even slowing aging itself. Beyond Earth, where microgravity, cosmic radiation, and oxidative stress accelerate cellular decline, targeting necrosis may also hold the key to preserving astronaut resilience and health on long-duration space missions, offering insights that could reshape human longevity both on and off the planet.
坏死是一种不受控制的细胞死亡，标志着生物退化的不可逆阈值。它源于希腊语nekros（死亡），是包括癌症以及肾脏、心脏、神经和肝脏疾病等众多疾病，更广泛地说，是衰老过程背后的关键机制。尽管坏死对发病率和死亡率有深远影响，但它仍然无法治疗，长期以来一直被视为生物学中混乱且不可避免的一个方面。本综述探讨了坏死的机制，并概述了新出现的证据所揭示的其对健康的深远影响。此外，我们还探讨了其作为一个改变游戏规则的治疗靶点的潜力。抑制坏死可能会彻底改变对急性和慢性年龄相关疾病（如癌症、肾脏疾病、心血管疾病（包括心脏病发作和中风）以及神经退行性疾病）的治疗方法，同时还能保持恢复力——甚至减缓衰老本身。在地球之外，微重力、宇宙辐射和氧化应激会加速细胞衰退，针对坏死可能也是在长期太空任务中保持宇航员恢复力和健康的关键，这为重塑地球上和地球外人类寿命提供了见解。
