Tag: kidney function

Categories : AgeingTags :

Could ‘Pausing’ Necrosis be the Final Frontier in Ageing and Medicine?

On By ModernMedia
Necrosis, unprogrammed cell death, spews a host of toxic molecules into the cellular environment. Credit: University College London

In a new study, published in Oncogene, a world-leading international team of scientists and clinicians explore the potential of necrosis to reshape our understanding and treatment of age-related conditions and even protect astronauts on longer journeys into space.

Challenging prevailing views, the paper brings together evidence from cancer biology, regenerative medicine, kidney disease, and space health to argue that necrosis is not merely an endpoint, but a key driver of aging that presents an opportunity for intervention.

Dr Keith Siew, an author of the study from UCL Centre for Kidney & Bladder Health, said: “Nobody really likes talking about death, even cell death, which is perhaps why the physiology of death is so poorly understood. And in a way necrosis is death. If enough cells die, then tissues die, then we die. The question is what would happen if we could pause or stop necrosis.”

Dr Carina Kern, lead author of the study and CEO of LinkGevity, a biotech company based at Cambridge’s Babraham Research Campus and part of the NASA Space-Health program, said: “Necrosis remains one of the last frontiers in medicine – a common thread across aging, disease, space biology, and scientific progress itself.”

Cells are the fundamental building blocks of life and can die in various ways. ‘Programmed’ forms of cell death are beneficial, carefully orchestrated processes that allow our tissues to replenish themselves and function well throughout life.

But ‘unprogrammed’ cell death, or necrosis, is an uncontrolled and catastrophic process that leads to tissue degeneration and biological decline.

At the centre of the necrotic process is calcium, a vital resource that effectively controls the cell by determining which functions are switched on or off. Calcium ions are normally maintained at a level that is 10 000 to 100 000 times higher outside the cell than inside.

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

This sparks a chain reaction that causes widespread inflammation and affects tissue repair, creating a snowball effect that ultimately leads to frailty and the onset of chronic age-related conditions such as kidney disease, heart disease and Alzheimer’s.

Dr Siew added: “When cells die, it’s not always a peaceful process for the neighbours.”

Dr Kern explains: “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 even aging itself.”

Notably, it is in the kidneys that necrosis may have its most devastating and underappreciated impact. Necrosis induces kidney disease, which can lead to kidney failure requiring a transplant or dialysis. By age 75 nearly half of all individuals develop some degree of kidney disease as part of the natural aging process.

Dr Siew added: “With kidney disease, there’s no one underlying reason that the kidneys fail. It could be a lack of oxygen, inflammation, oxidative stress, a build-up of toxins, and so on. All of these stressors eventually lead to necrosis, which initiates a positive feedback loop that spirals out of control, leading to kidney failure. We can’t stop all of these stressors, but if you could intervene at the point of necrosis, you’d effectively achieve the same result.”

Another area where interrupting necrosis could have a big impact is spaceflight, where astronauts often experience accelerated ageing and kidney-related decline due to the effects of low gravity and exposure to cosmic radiation. A 2024 study involving Dr Siew demonstrated that the human kidney may be the ultimate bottleneck for long-duration space missions.

The authors say finding solutions to this accelerated aging and kidney disease may be the final frontier for human deep space exploration.

Dr Kern said: “In many age-related diseases – affecting diverse organs such as the lungs, kidneys, liver, brain, and cardiovascular system – relentless cascades of necrosis fuel the progression of disease. This is often alongside impaired healing that leads to fibrosis, inflammation and damaged cells. Each cascade triggers and amplifies the next.

“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.”

Source: University College London

Categories : Cardiovascular Disease Diseases, Syndromes and ConditionsTags :

Even Modest Drop in Kidney Function is Linked to Greater Health Risks

On By ModernMedia
Photo by Robina Weermeijer on Unsplash

A Canadian study of more than 8 million adults suggests that even a modest loss of kidney function is associated with increased health risks. The study, published in The BMJ, could lead to better approaches to prevent chronic kidney disease and related conditions, particularly in younger adults.

“The dogma is that healthy, young adults don’t need to worry about kidney function unless it drops to around 50% of the normal level, but our research suggests that even a more modest 20–30% drop may have consequences and we may want to have earlier conversations about prevention and monitoring,” explained senior author Dr Manish Sood at the University of Ottawa.

The research team used health records from 2008 to 2021 for every Ontario, Canada adult aged 18–65 who had at least one blood test for kidney function, but no history of kidney disease. They found that 18% of those in the 18–39 age group had kidney function that was modestly below normal levels, but not low enough to be diagnosed with chronic kidney disease. Individuals in this ‘grey zone’ faced a modestly increased risk of kidney failure, death and cardiovascular events.

For example, in young adults (age 18–39), a 20–30% loss in kidney function was associated with a 1.4-fold increase in death, 1.3-fold increase in a cardiac event and a 6-fold increase in the risk of kidney failure. The absolute risk of any of these events was still low at less than 2 per 1000.

“Thankfully, the absolute risk for any one individual with kidney function in this grey zone is low, but when we look at the whole population, the impact could be quite significant,” said co-senior author Dr Greg Knoll, senior scientist, nephrologist and Head of the Department of Medicine at The Ottawa Hospital and the University of Ottawa. “We need further research to confirm these findings and then see if we can reduce the risk through lifestyle modification.”

While the blood creatine test for kidney function is relatively inexpensive and readily available, the researchers are not suggesting routine testing for all individuals at this time. However, if an individual has had a kidney test that shows a modest reduction in function, it could prompt consulting health care provider. All individuals can also reduce their risk of kidney disease by eating a healthy diet with lower salt, exercising regularly and limiting alcohol intake.

Dr. Sood and his colleagues previously developed the Project BigLife Chronic Kidney Disease calculator to help individuals calculate their kidney disease risk and see the impact of lifestyle changes. The calculator will continue to be refined as new research arises.  

Source: EurekAlert!