LinkGevity, a Cambridge-based AI-driven drug discovery company, has made a notable contribution to the burgeoning field of longevity science through its collaboration on a significant paper published in Oncogene. Titled "Necrosis as a fundamental driver of loss of resilience and biological decline: What if we could intervene?" this work merges insights from various prestigious institutions, including the Mayo Clinic, Mass General Brigham, NASA's Space-Health programme, and several universities. The authors propose a paradigm shift in understanding necrosis—not merely as a final stage of cell death but as a pivotal mechanism underpinning the processes of aging and the development of age-related diseases.
Historically, necrosis was viewed as an unregulated, terminal event in cellular life. However, the authors argue that it serves a much larger role in the biological decline that accompanies aging. Central to this process is calcium, a vital ion that ordinarily maintains cellular functions by keeping concentrations significantly higher outside the cell than within. An imbalance, however, can lead to catastrophic consequences, as a calcium surge prompts uncontrolled cellular processes, eventually culminating in necrosis. This destructive form of cell death unleashes toxic substances that trigger inflammation and inhibit tissue repair, creating a vicious cycle that exacerbates frailty and sets the stage for a host of chronic illnesses, including cancer, neurodegenerative disorders, and, particularly insidiously, kidney disease.
In light of these revelations, researchers highlight necrosis as not just an outcome but an active contributor to age-related degeneration, offering fertile ground for innovative therapeutic interventions. Dr Carina Kern, LinkGevity's CEO and lead author of the paper, asserts, “Necrosis has been hiding in plain sight… It’s 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 implications of targeting necrosis are profound. In the context of cancer, for example, necrosis has been linked to increased tumour aggression and therapeutic resistance. In cardiovascular events such as strokes and heart attacks, it is pivotal in tissue death. The research underscores particularly alarming implications for kidney health; advancements in understanding necrosis could pave the way for breakthroughs in treating kidney disease, a condition affecting approximately half of individuals over 75. Co-author Prof Joseph Bonventre from Harvard Medical School emphasises this potential, declaring it “a fundamental breakthrough with far reaching impact”.
The urgency of these findings is underscored in extreme environments, such as in space, where astronauts experience accelerated aging and renal decline due to low gravity and cosmic radiation. Prof Damian Biley of the European Space Agency has pointed out that addressing necrosis is crucial for making long-duration missions, like those to Mars, viable. This focus on necrosis not only promises a deeper understanding of aging on Earth but also harbours transformative potential for the future of space exploration.
As the field of longevity science continues to evolve, LinkGevity is at the forefront, employing its proprietary Blueprint Mapping platform to identify and target the pathological pathways that lead to aging and related diseases. The urgency of this work cannot be overstated. With current treatments for kidney disease limited primarily to dialysis and transplants, the number of cases is projected to rise, rendering global healthcare systems increasingly strained.
If the proposed strategies for targeting necrosis prove effective, they could revolutionise not only how we treat a range of chronic diseases but also how we conceptualise aging itself. By rethinking the role of necrosis in biological processes, researchers aim to unify the treatment approaches for multiple chronic diseases and ultimately mitigate the effects of aging. Nearly five decades of research has yielded few solutions for the complexities of aging, but with this new focus on necrosis, a significant turning point in medical science may finally be within reach.
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Source: Noah Wire Services