Babraham Research Campus-based LinkGevity understands how necrosis is key to slow ageing

LinkGevity’s latest paper identifies how necrosis, traditionally seen as a terminal cell death process, may actually be a key driver of ageing and age-related diseases.

The AI-driven drug discovery company, which has an R&D lab at the Babraham Research Campus, worked with a world-leading international team of clinicians and scientists from institutions including Harvard Medical School, the Mayo Clinic, NASA’s space-health program, and the European Space Agency for the study.

Titled ‘Necrosis as a fundamental driver of loss of resilience and biological decline: What if we could intervene?’, the paper has been published in Springer Nature’s Oncogene, one of the world's leading cancer journals.

It explains how targeting necrosis could open up new therapeutic avenues for diseases like kidney failure, neurodegeneration, and cardiac disease - and could even slow the aging process itself. Insights from space health show that astronauts face accelerated aging and kidney decline due to unique space conditions, making necrosis a critical target for space exploration and health in space.

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

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.

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

In neurodegenerative diseases such as Alzheimer’s and Parkinson’s, necrosis drives neuronal cell loss and inflammation.

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 aging – 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’s CEO, Dr Carina Kern, based at the Babraham Research Campus, Cambridge, 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.”