A form of cell death, the process of necrosis, could represent a highly promising way to alter the course of human aging, disease and even space travel, according to a new study by researchers at UCL, drug discovery company Linkage and the European Space Agency (ESA).
In the study, I was published Nature Oncogenea world-class international team of scientists and clinicians explores the potential of necrosis—when people die unexpectedly as a result of infection, injury, or disease—to reshape our understanding and treatment of age-related conditions.
Challenging prevailing views, the paper brings together evidence from cancer biology, regenerative medicine, kidney disease, and space health to argue that necrosis is not simply an endpoint, but a key driver of aging that presents an opportunity for intervention.
Study author Dr Keith Siew, from the UCL Center for Kidney and Bladder Health, said: “No one really likes to talk about death, even cell death, which is why the physiology of death is so understudied.
Dr Karina Korn, CEO of Linkagety, a biotech company based at Cambridge’s Babarham Research Campus and part of the NASA Space Health Programme, said: “Necrosis is one of the last frontiers in medicine.
Cells are the basic building blocks of life and can die in a variety of ways. ‘Programmed’ forms of cell death are beneficial, carefully orchestrated processes that allow our tissues to replenish themselves and function well throughout life.
But ‘unregulated’ cell death, or necrosis, is an uncontrolled and destructive process that leads to tissue degeneration and biological decline.
At the heart of the necrotic process is calcium, a key resource that effectively controls the cell by determining which functions are turned on or off. Calcium ions are normally maintained at a level that is 10,000 to 100,000 times greater than inside the cell.
When this delicate balance fails, calcium floods the cell like an electrical short circuit, throwing the cell into chaos. Unlike programmed death, where cells die in a systematic manner, necrosis causes cells to rupture, releasing toxic molecules into surrounding tissues.
This sets off a chain reaction that causes widespread inflammation and impairs tissue repair, creating a snowball effect that ultimately leads to frailty and the onset of age-related chronic conditions such as kidney disease, heart disease and Alzheimer’s.
Dr Siu added: “When cells die, it’s not always a peaceful process for the neighbours.”
Dr. Korn explained: “Necrosis is hidden in plain sight. As a final stage of cell death, it has been largely overlooked. But growing evidence suggests that it is much more than a central mechanism. It is a central mechanism by which systemic degeneration not only originates but propagates. Cardiac disease, neurodegeneration, and even aging itself.”
In particular, it is in the kidneys that necrosis can have its most devastating and least impact. Necrosis induces kidney disease, which can lead to kidney failure requiring a transplant or dialysis. Half of all people by age 75 develop some degree of kidney disease as part of the natural aging process.
Dr. Seo added: “With kidney disease, there is no one underlying reason why the kidneys fail. It can be lack of oxygen, inflammation, oxidative stress, toxic build-up, etc. If you add all of these stressors can lead to necrosis, which can lead to a positive feedback stress. Necrosis, you’ll effectively get the same result.”
Another area where disruptive necrosis can have a major impact is spacelight, where astronauts often experience accelerated aging and kidney failure due to the effects of low gravity and exposure to cosmic radiation. A 2024 study involving Dr. Siu has revealed that the human kidney may be the ultimate barrier to long-duration space missions.
Finding a solution to this accelerated aging and kidney disease could be the final frontier for human deep space exploration, the authors say.
Professor Damian Bailey, author of the paper from the University of South Wales and Chair of the European Space Agency (ESA) Life Sciences Working Group, said: “Targeting necrosis not only offers the potential to transform longevity on Earth, but also advances the frontiers of space exploration.
Dr. Korn added: “In many age-related diseases—which affect various organs such as the lungs, kidneys, liver, brain, and cardiovascular system—an unrelenting cascade of necrosis drives disease progression. This is often accompanied by impaired healing.
“If we can stop necrosis, even temporarily, we will stop these destructive cycles at their source, enabling normal bodily processes and cell division to resume – and possibly even regeneration.”
The paper is a collaborative effort of experts and scientists from institutions including the UCL Division of Medicine, Brigham and Women’s Hospital affiliated with Harvard Medical School, the Mayo Clinic, the NASA Space Health Program, the MRC Laboratory of Molecular Biology, the University of South Wales, and the European Space Agency.
