| It is a cold, dark January here in the Northern Hemisphere. What better time to talk about cell death? Alas, every cell that lives will one day die, but typical cell death isn't disruptive, chaotic, or injurious. It's part of life. In the early 1970s, researchers described a formal, highly controlled death process known as apoptosis. It is widespread across the tree of life and regulated by the same genes in a diverse range of species, from worms to mammals.
When a cell is stressed or receives a particular signal from a neighboring cell, it starts to deteriorate systematically and safely through apoptosis. The cell shrinks; its internal contents condense and then collapse. Finally, it breaks apart into tiny sacs, known as blebs, which can be taken up by surrounding cells that can reuse the molecular parts. Crucially, apoptosis doesn't hurt the dying cell's neighbors; in uncontrolled cell death processes, such as necrosis, a sick cell bursts open, releasing toxic compounds that can damage surrounding cells. By contrast, apoptosis is like a controlled demolition.
The ability of cells to die in this way is critical for the survival of multicellular species. In animals with nervous systems, for example, early development can be a violent time: A growing brain has many more cells than it needs and must shape and refine itself by killing off many of those neurons. When apoptosis goes awry, it can lead to a slew of complications. Cancer is composed of cells that should die but don't, while people with autoimmune diseases are riddled with cells that should not die but do.
Though the process appears simple, questions of cellular life and death conceal great complexities. "The whole field of cell death is plagued by this question of defining what a dead cell is," said the cell biologist Shai Shaham in a 2024 episode of our podcast The Joy of Why. Researchers are continuing to unpack what it means for a cell to live or die — and even to come back to life.
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The origin of programmed cell death likely dates back billions of years, to ancient bacteria. In one study, researchers found that 2 million years ago, the first eukaryotes — a cell type with complex organization, including a nucleus and mitochondria, like those that make up our bodies — likely already had the tools for apoptosis, inherited from simpler bacterial forebears. It's still debated why exactly the process originated. Some researchers speculate that ancient bacteria may have used these tools as defenses from external predators. Others propose that apoptosis evolved in single-celled organisms as a method of self-sacrifice for the good of the population, to prevent the spread of disease, for instance.
Cell death must be final, right? Turns out it's not. Under the right conditions, some cells that have undergone apoptosis can resurrect themselves in a process called anastasis, after the Greek word for "rising to life." This process both repairs cellular damage and restarts cellular processes. Just as apoptosis is a highly controlled process, so is anastasis; likewise, researchers have found anastasis in many different organisms, from fruit flies to rodents. It may have evolved as a way to hit the brakes on widespread apoptosis after severe but temporary stress, to limit permanent tissue damage.
Sometimes what may look like death is more like a really long nap. Most life on Earth is dormant: When faced with harsh conditions, like cold temperatures or a dearth of food, many species can slow down their metabolism and enter dormancy. But how? One study identified a protein, called a hibernation factor, that "pulls the emergency brake" in cells in Arctic permafrost by halting the creation of new proteins. Dormancy isn't unique to microbes: In the human body, oocytes (egg cells) and immune system lymphocytes can stay dormant for long periods of time. | 
