Scientists Target Cell Death to Unlock Aging Secrets

What if the key to extending human life—both on Earth and in space—lies not in preventing death, but in pausing it?

A new study published in Nature Oncogene suggests that necrosis, an uncontrolled form of cell death, may be the missing link between aging, disease, and our ability to explore deep space. Unlike the orderly death that healthy cells undergo, necrosis creates chaos within tissues, triggering cascading damage that researchers now believe drives everything from cancer progression to kidney failure.

The Calcium Connection

The research reveals that calcium serves as the ultimate cellular controller, maintained at levels 10,000 to 100,000 times higher outside cells than inside them. When this delicate balance fails, calcium floods into cells like an electrical short circuit, pushing them into what Dr. Keith Siew from UCL describes as chaos.

“When cells die, it’s not always a peaceful process for the neighbours,” said Dr. Siew, highlighting how necrotic cell death spreads damage to surrounding healthy tissue.

This calcium overload activates destructive enzymes called calpains and phospholipases, which break down cellular structures from within. The study details how these enzymes destroy internal compartments like lysosomes, releasing hazardous contents including cathepsins, oxidative agents, and various destructive proteins into the cell’s interior.

Beyond Cancer: A Universal Problem

While cancer research has long recognized necrotic cores within tumors, this study connects necrosis to a much broader range of conditions. The researchers found that necrosis creates positive feedback loops—once it starts, it triggers more cell death in neighboring tissues, creating what they term “patho-pathways” that drive aging and disease.

Dr. Carina Kern, the study’s lead author and CEO of LinkGevity, explained: “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.”

The kidney emerges as a particularly vulnerable organ. By age 75, nearly half of all individuals develop kidney disease, largely driven by necrosis of renal tubular epithelial cells. Unlike other organs that can regenerate more easily, kidney damage from necrosis often becomes permanent, creating scar tissue and chronic inflammation.

The Space Connection

Perhaps most intriguingly, the research links necrosis to challenges facing astronauts on long-duration space missions. Cosmic radiation and microgravity accelerate the same cellular damage seen in earthbound aging, with the kidney potentially serving as the limiting factor for deep space exploration.

Professor Damian Bailey from the European Space Agency noted: “Targeting necrosis offers potential to not only transform longevity on Earth but also push the frontiers of space exploration. In space, the same factors that cause aging on Earth are made worse by cosmic radiation and microgravity—speeding up degeneration dramatically.”

A 2024 study cited in the research demonstrated that kidney function may be the ultimate bottleneck for missions to Mars and beyond, as space-induced necrosis accelerates kidney aging far beyond what occurs on Earth.

Key Research Findings:

• Necrosis triggers release of damage-associated molecular patterns (DAMPs) that amplify inflammatory responses
• Calcium homeostasis disruption serves as the primary trigger for necrotic cascades
• Necrotic feedback loops contribute to cancer metastasis and treatment resistance
• Space environments accelerate necrosis through combined radiation and microgravity effects

From Theory to Treatment

The study introduces the “Blueprint Theory” of aging, which positions necrosis as a critical node where multiple disease pathways converge. Unlike programmed cell death, which follows genetic instructions and serves beneficial purposes, necrosis represents pure biological chaos—making it both more dangerous and potentially easier to target without unintended consequences.

Current approaches to preventing necrosis have largely failed because they target downstream effects rather than root causes. Calcium channel blockers showed initial promise in animal studies, but clinical trials revealed their benefits came from improving blood flow rather than directly preventing necrotic cell death.

What makes this research particularly compelling? The authors argue that necrosis lacks the genetic regulation of other cellular processes, meaning interventions might avoid the trade-offs seen with other anti-aging approaches. Blocking programmed cell death can increase cancer risk, but stopping chaotic necrosis should theoretically be safer.

The Path Forward

The implications extend far beyond medicine. Necrosis currently limits organ preservation to just 4-6 hours, hampering transplant success. It prevents successful cryopreservation of complex tissues and limits the effectiveness of stem cell therapies, where most transplanted cells die within days.

As Dr. Kern observed: “If we could prevent necrosis, even temporarily, we would be shutting down these destructive cycles at their source, enabling normal physiological processes and cell division to resume—and potentially even allowing for regeneration.”

The research team, spanning institutions from UCL to Harvard Medical School to NASA’s Space-Health program, represents an unusual convergence of cancer biology, kidney disease research, and space medicine. Their collaborative approach reflects necrosis’s role as what they call “one of the last frontiers in medicine.”

Whether targeting necrosis will prove feasible remains an open question. But as humanity prepares for missions to Mars and grapples with an aging population on Earth, understanding this fundamental process of cellular chaos may hold keys to extending both lifespan and our reach into the cosmos.