A Destructive Form of Cell Death Might Be The Key To Slowing The Human Aging Process

Experts across scientific and clinical fields, writing in Nature Oncogene, explore the emerging role of necrosis in aging—pointing to its potential to reshape how we understand and treat age-related conditions

/EIN News/ -- CAMBRIDGE, United Kingdom, May 29, 2025 (GLOBE NEWSWIRE) -- LinkGevity, an AI-driven drug discovery company focused on revolutionising the treatment of aging and age-related diseases, today announces its contribution to the publication of a paper in Springer Nature’s Oncogene, “Necrosis as a fundamental driver of loss of resilience and biological decline: What if we could intervene?” (1).

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 aging 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 aging 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 center 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 aging. 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 aging 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 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.

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 aging said: “Development of an intervention targeting necrosis would be a fundamental breakthrough with far reaching impact”.

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

Reference

(1) Necrosis as a fundamental driver of loss of resilience and biological decline: What if we could intervene?

Notes to Editors

About LinkGevity
LinkGevity is an AI-driven drug discovery company focused on revolutionising the treatment of ageing and age-related disorders, such as chronic kidney disease. LinkGevity’s proprietary Blueprint Mapping platform identifies & targets key pathological pathways which are the molecular “source” of destructive cascades underlying multiple age-related conditions and biological decline. By using therapeutics that precisely target these “patho pathways”, LinkGevity aims to halt age-related deterioration.

LinkGevity was selected as one of only 12 global innovations for the NASA sponsored Space-Health programme for its potential to combat accelerated aging and kidney decline in astronauts. The company has also earned several prestigious grants from the European Union (EU Horizon) and the UK Government’s Innovation Agency. It has also secured investment from The Francis Crick Institute (KQ Labs Program), Europe’s largest biomedical research centre.

The company is based at the Babraham Research Campus, affiliated with the UK’s University of Cambridge. For more information see the website and follow the company on LinkedIn.

About Kidney Disease

The kidneys are particularly susceptible to necrosis and tissue degeneration due to their high metabolic activity, which is essential for removing waste products from the body and regulating fluid levels. Necrosis of kidney cells—especially tubular cells (Renal Tubular Necrosis, RTN), which are central to waste filtration—drives the progression of kidney disease. Ongoing necrosis sets off a cascade of positive feedback loops that block proper repair, leading to fibrosis, cellular aging, and immune dysfunction—ultimately turning kidney injury into chronic kidney disease (CKD).

With no approved therapies to inhibit necrosis, kidney disease remains the 9th leading cause of death globally, according to the World Health Organization. Despite decades of research, current treatments are limited to dialysis and organ transplantation. Projections suggest that within the next 10 years, global healthcare systems will struggle to meet the rising costs of dialysis. In response, many countries, including the UK, have declared kidney disease a public health emergency.

Media Contacts

LinkGevity

Serena Kern-Libera, LinkGevity’s COO and co-founder
serena@linkgevity.com

Scius Communications

Daniel Gooch +447747875479
daniel@sciuscommunications.com