LinkGevity leans on space research to battle necrosis role in ageing

The paper details how necrosis, traditionally seen as a terminal cell death process, may actually be a key driver of ageing and age-related diseases. It explains how targeting necrosis could open up new therapeutic avenues for diseases like kidney failure, neurodegeneration, and cardiac disease and even slow the ageing process itself.

Insights from space health show that astronauts face accelerated ageing and kidney decline due to unique space conditions, making necrosis a critical target for space exploration and health in space.

This research is a significant step toward redefining how we approach ageing and chronic disease treatment, with the potential to impact healthcare on Earth and space exploration.

The paper is a collaborative effort by a top international team of clinicians and scientists from institutions including the Mayo Clinic, Mass General Brigham, NASA Space-Health program, MRC Laboratory of Molecular Biology, University of South Wales (USW), University College London’s Medical School and the European Space Agency.

The authors explain how necrosis, a form of cell death historically viewed as an unregulated and terminal event, may in fact represent one of the most fundamental and targetable mechanisms driving human ageing and age-related disease. The paper brings together evidence from cancer biology, regenerative medicine, kidney disease, and space health to make the case that necrosis is more than a biological endpoint: it may be the crux of how cells and tissues fail as people age.

The paper delves into how ageing is driven by a silent cellular battle. Cells are the fundamental building blocks of life. Cell death can either be a beneficial and carefully orchestrated "programmed" process to maintain survival, or an uncontrolled and catastrophic process that defines biological degeneration — termed necrosis, rooted in the Greek nekros, the word for "death."

At the centre of necrosis is calcium, a vital ion that, in effect, controls the "wiring" of a cell. Calcium determines which cellular functions are switched on or off with calcium ions normally maintained at a level that is 10,000 to 100,000 times higher outside the cell vs inside.

When this finely tuned balance fails, calcium floods the cell like an electrical short circuit, triggering multiple cellular processes simultaneously and pushing the cell into irreversible chaos. Unlike programmed death, where cells dismantle in an organised manner, necrosis causes cells to rupture, spilling toxic molecules into surrounding tissues.

But the damage doesn’t stop there. As the paper details, this sparks a chain reaction that spreads like a cascade failure, causing widespread inflammation and derailing proper tissue repair processes.

This creates a self-perpetuating cycle – a positive feedback loop that amplifies tissue damage, drives destructive processes like cellular senescence and fibrosis, and undermines systemic resilience. In turn, these processes fuel both frailty and the onset of multiple chronic diseases associated with ageing.

Crucially, challenging prevailing views, the paper highlights that necrosis is not merely an endpoint, but a central, active driver of ageing— and one that presents an opportunity for a game-changing intervention, capable of transforming our entire understanding of medicine and health.

Lead author and LinkGevity CEO, Dr Carina Kern, based at the Babraham Research Campus, said: “Necrosis has been hiding in plain sight—as a final stage of cell death, it’s been largely overlooked. But mounting evidence shows it’s far more than an endpoint.

“It’s a central mechanism through which systemic degeneration not only arises but also spreads. That makes it a critical point of convergence across many diseases. If we can target necrosis, we could unlock entirely new ways to treat conditions ranging from kidney failure to cardiac disease, neurodegeneration and excitingly even ageing itself.”

The review details how necrosis is implicated in several major disease pathways. In cancer, it contributes to tumour aggression, metastasis, and resistance to therapy. In stroke and heart attack, it is the dominant mechanism of cell and tissue death. In neurodegenerative diseases such as Alzheimer’s and Parkinson’s, necrosis drives neuronal cell loss and inflammation.

Notably, it is in the kidneys that necrosis may have its most devastating and under-appreciated impact. Necrosis induces kidney disease, which by the age of 75 years it is anticipated half of all individuals develop with natural ageing – often requiring a transplant or dialysis.

Prof Joseph Bonventre, co-author on the paper and a leading expert on kidney disease at Mass General Brigham as well as professor of Medicine at Harvard Medical School, whose work has focused on the vulnerability of the kidneys to damage and ageing said: “Development of an intervention targeting necrosis would be a fundamental breakthrough with far reaching impact”.

In environments of accelerated ageing such as spaceflight, astronauts often experience rapid onset of ageing and kidney-related decline. This is due to low gravity and cosmic radiation.

This accelerated ageing and kidney disease may be the final hurdle in making long duration missions, such as to Mars a reality.

Prof. Damian Biley, Chair of the Life Science Working Group of the European Space Agency (ESA) who is also a leading neurovascular and longevity expert at USW, and who co-led the paper said: “Targeting necrosis offers potential to not only transform longevity on earth but also push the frontiers of space exploration.”

Dr Keith Siew, UCL Centre for Kidney & Bladder Health and Co-lead of the London Tubular Centre, said: “Our work highlights one of the most critical biological barriers to extending healthspan and charts a path toward developing game-changing interventions to prevent the onset of multiple chronic diseases with age.”

The authors emphasise that targeting necrosis could provide a unifying approach to treating multiple chronic diseases and even slowing or halting degeneration with age. If validated therapeutically, such an approach could represent a turning point in medicine.