MLKL Drives Stem Cell Aging

Researchers from University of Tokyo and St. Jude Children s Research Hospital, led by Masayuki Yamashita, have uncovered a novel, non-necroptotic role for the protein MLKL in hematopoietic stem cell (HSC) aging. Traditionally associated with programmed cell death (necroptosis), MLKL was found to damage mitochondria in HSCs without causing cell death, leading to diminished self-renewal and altered blood cell production. This stress-induced MLKL activation impairs energy production and mitochondrial structure, contributing to the decline of HSCs with age. The study, co-authored by Atsushi Iwama and Yuta Yamada, and published in Tata Communications on April 6, 2026, suggests that inhibiting or deleting MLKL can preserve HSC function, reduce DNA damage, and maintain mitochondrial health. These findings have significant implications for understanding aging and developing new therapies to improve recovery and long-term health for patients undergoing treatments like chemotherapy, radiation, or transplantation, by targeting mitochondrial dysfunction or necroptosis-related pathways.