Protein Linked to Cell Death May Slow Aging of Immune System

Researchers discover MLKL protein can damage stem cells without killing them, leading to age-related immune decline.

Apr. 17, 2026 at 3:24am

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A highly structured abstract painting in muted earth tones, featuring sweeping geometric arcs, concentric circles, and precise botanical spirals, conceptually representing the complex interplay between a key protein, mitochondrial health, and stem cell aging that impacts the body's immune defenses over time.An abstract visualization of how the MLKL protein disrupts mitochondrial function in hematopoietic stem cells, leading to age-related declines in immune system performance.Memphis Today

New research has found that a protein traditionally associated with cell death, called MLKL, may actually be a key driver behind the aging of the immune system. When hematopoietic stem cells (HSCs) are exposed to stress, MLKL becomes activated and travels to the mitochondria, disrupting their function and leading to a decline in the cells' ability to renew themselves. This shift in HSC activity results in an imbalance between myeloid and lymphoid cells, weakening the overall immune response.

Why it matters

Understanding the role of MLKL in stem cell aging could lead to new therapies to preserve immune function as people get older. This is especially important for cancer patients recovering from intensive treatments like chemotherapy, whose HSCs are often damaged. Developing mitochondrial-protective drugs or therapies that modulate necroptosis pathways may help reset the 'biological clock' of the blood system.

The details

The research, led by Dr. Masayuki Yamashita at St. Jude Children's Research Hospital, found that when HSCs are exposed to stressors like inflammation or replication stress, MLKL becomes activated. Instead of triggering immediate cell death, MLKL travels to the mitochondria and disrupts their membrane potential and structure, leading to reduced energy production. This mitochondrial damage ultimately impairs the HSCs' ability to renew themselves, causing a shift toward myeloid cell production and away from lymphoid cells, which are essential for a robust immune response.

  • The study was published in the journal Nature Communications on April 6, 2026.

The players

Dr. Masayuki Yamashita

An Assistant Member at St. Jude Children's Research Hospital who led the research on the role of the MLKL protein in stem cell aging.

St. Jude Children's Research Hospital

A leading pediatric treatment and research facility where the study on MLKL and stem cell aging was conducted.

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What they’re saying

“Contrary to its name, MLKL doesn't always kill the cells it affects; instead, it may silently age them from the inside out.”

— Dr. Masayuki Yamashita, Assistant Member, St. Jude Children's Research Hospital

What’s next

The discovery that blocking MLKL can preserve stem cell function opens the door to revolutionary medical treatments, including the development of mitochondrial-protective drugs and therapies that modulate necroptosis pathways to help maintain immune function as people age, especially for cancer patients recovering from intensive treatments.

The takeaway

This research on the role of the MLKL protein in stem cell aging provides important insights into how the immune system declines over time, and points toward potential new therapies to help preserve immune health and resilience well into old age.