apoptosis 于20世纪70年代初被正式描述为一种高度受控的细胞死亡程序，并在生命之树上广泛存在；从蠕虫到哺乳动物，调控它的基因在不同物种间高度保守。受压力或邻近细胞信号触发时，细胞按步骤安全解体：体积缩小，内部成分凝缩并崩塌，最终分裂成称为 blebs 的小囊，被周围细胞吞噬并回收利用。与之相对，necrosis 等失控死亡会使细胞破裂并释放有毒化合物，损伤邻近细胞；apoptosis 更像一次“受控爆破”。

这种可控的死亡能力对多细胞生存是关键，尤其在有神经系统的动物中：发育早期的大脑会产生多于所需的细胞，并通过清除大量神经元来塑形与精炼。apoptosis 失常与疾病谱系相关：癌症由本应死亡却未死亡的细胞构成，而自身免疫病则充斥着本不该死亡却发生死亡的细胞。尽管机制表面简洁，其定义仍复杂；细胞生物学家 Shai Shaham 在 2024 年播客 The Joy of Why 中指出，该领域长期受困于“如何界定死细胞”。

程序性细胞死亡的起源可能可追溯至数十亿年前的古细菌；一项研究提出，200万年前最早的真核生物已具备 apoptosis 工具，可能源自更简单的细菌祖先。其起源目的仍有争论：或为抵御外部捕食者的防御工具，或为单细胞群体的利他性自我牺牲以阻断疾病传播。死亡也未必终局：在适当条件下，经历 apoptosis 的细胞可通过 anastasis “复起”，修复损伤并重启过程，该现象见于从果蝇到啮齿类的多种生物。与死亡相似的另一策略是休眠：许多物种在寒冷或缺粮时降低代谢；一项研究在北极永久冻土中识别出 hibernation factor，可通过停止新蛋白合成来“拉下紧急刹车”，而在人类中，卵母细胞与免疫淋巴细胞也可长期休眠。

Apoptosis was formally described in the early 1970s as a highly controlled cell-death program and is widespread across the tree of life; from worms to mammals, the genes that regulate it are strongly conserved. When stress or a neighbor’s signal triggers it, a cell dismantles itself stepwise and safely: it shrinks, its contents condense and collapse, and it breaks into small sacs called blebs that surrounding cells engulf and recycle. By contrast, uncontrolled death such as necrosis can rupture cells and spill toxic compounds that injure nearby cells; apoptosis functions more like a “controlled demolition.”

This capacity for orderly death is critical to multicellular survival, especially in animals with nervous systems: early brain development produces more cells than needed and refines circuitry by eliminating many neurons. When apoptosis malfunctions, it maps onto disease: cancer consists of cells that should die but do not, while autoimmune disease involves cells that should not die but do. Despite its clean outline, definitions remain hard; cell biologist Shai Shaham noted on a 2024 episode of the podcast The Joy of Why that the field is dogged by the problem of defining what a dead cell is.

The origins of programmed cell death may reach back billions of years to ancient bacteria; one study suggests the first eukaryotes already had apoptosis tools 2 million years ago, likely inherited from simpler bacterial forebears. Why it arose remains debated: a defense against predators, or single-celled self-sacrifice to limit disease spread. Death is not always final: under certain conditions, cells that underwent apoptosis can revive via anastasis, repairing damage and restarting processes, observed from fruit flies to rodents. Another death-adjacent strategy is dormancy: many species slow metabolism in cold or famine; one study found a hibernation factor in Arctic permafrost that halts new protein production like an emergency brake, and in humans, oocytes and immune lymphocytes can also remain dormant for long periods.