What if the key to prolonging human life (both on earth and in space) is not to prevent death but to pause death?
A new study published on natural oncogenes suggests that necrosis is an uncontrolled form of cell death, possibly a missing link between aging, disease and our ability to explore deep space. Unlike the orderly deaths experienced by healthy cells, necrosis creates chaos within the tissue, triggering cascade damage, researchers now believe everything from cancer progression to renal failure.
Calcium connection
The study shows that calcium is the ultimate cellular controller, with external cells at levels 10,000 to 100,000 times higher than internal calcium. When this delicate balance fails, calcium will pour into cells like an electrical short circuit, pushing them into what Dr. Keith Siew of UCL calls the chaos.
“When cells die, it’s not always a peaceful process for neighbors,” Dr. Siew said.
This calcium overload activates destructive enzymes called calproteases and phospholipases, which partially dissolve cellular structures. The study details how these enzymes destroy internal compartments such as lysosomes, releasing dangerous content including cathepsin, oxidants and various destructive proteins.
Beyond Cancer: A Common Problem
Although cancer studies have long identified necrotic nuclei in tumors, the study links necrosis to a wider range of diseases. Researchers found that necrosis creates a positive feedback loop—once it begins, it triggers more cell death in adjacent tissues, creating “sick pathways” that drive aging and disease.
“Neutation has been hidden in the obvious sight. As the final stage of cell death, it has been largely ignored. However, there is growing evidence that it goes far beyond the end point. It is a core machinery, and systemic degeneration is not only radiating.”
The kidney is a particularly fragile organ. By the age of 75, almost half of individuals develop renal disease, which is largely driven by necrosis of tubular epithelial cells. Unlike other organs that can be more regenerated, necrotic kidney damage often becomes permanent, creating scar tissue and chronic inflammation.
Space connection
Perhaps most interestingly, the study links necrosis to the challenges faced by astronauts in long-term space missions. Cosmic radiation and microgravity accelerate the same cellular damage in Earth’s aging, and the kidneys may be a limiting factor in deep space exploration.
Professor Damian Bailey of the European Space Agency noted: “Targeted necrosis can not only change life span on Earth, but also drive the boundaries of space exploration. In space, the same factors that cause the aging on Earth are worsened by cosmic radiation and microradiation, allowing degeneration to greatly accelerate degeneration.”
A 2024 study cited in the study shows that renal function may be the ultimate bottleneck for missions on Mars and beyond, as space-induced necrosis accelerates kidney aging far beyond what happens on Earth.
Key research results:
- Necrosis triggers release of damage-related molecular patterns (wet) to amplify inflammatory response
- Calcium homeostasis damage is the main trigger for necrotic cascade
- Necrotic feedback loop helps cancer metastasis and treatment resistance
- Space environment accelerates necrosis through radiation and microgravity effects
From theory to treatment
The study introduces the “blueprint theory” of aging, which locates necrosis as a key node in the fusion of multiple disease pathways. Unlike programmed cell death that follows genetic instructions and has beneficial purposes, necrosis represents a pure biological confusion – making it both dangerous and easier to target without unintended consequences.
Current methods of preventing necrosis have largely failed because they target downstream effects rather than root causes. Calcium channel blockers show initial promise in animal studies, but clinical trials have shown that their benefits come from improving blood flow rather than directly preventing necrotic cell death.
What makes this study particularly compelling? The authors argue that necrosis lacks genetic regulation of other cellular processes, which means that interventions may avoid the trade-offs seen using other anti-aging methods. Blocking programmed cell death increases the risk of cancer, but stops chaotic necrosis if it is theoretically safer.
The way forward
These implications are far beyond the scope of medicine. Necrosis currently limits organ preservation to only 4-6 hours, thus hindering the success of transplantation. It prevents successful cryopreservation of complex tissues and limits the effectiveness of stem cell therapy where most transplanted cells die within a few days.
As Dr. Kern observed: “If we can prevent necrosis, even temporarily, we will close the source of these destructive cycles, thereby restoring normal physiological processes and cell division, and potentially even allowing regeneration.”
The research team spans the institutions of space health programs from UCL to Harvard Medical School to NASA, representing an abnormal fusion of cancer biology, kidney disease research, and space medicine. Their collaborative approach reflects the role of necrosis, known as “one of the last boundaries of medicine.”
Whether targeted necrosis will prove feasible remains an open question. But as humans prepare for their mission to Mars to fight the aging population on Earth, understanding this basic cellular mess may have the key to extend lifespan and our coverage into the universe.
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