Researchers have induced a senescent-like state in worms by modifying the activity of the transcription factor TFEB. Under normal conditions, worms experience regeneration and signs of rejuvenation after fasting followed by refeeding. However, when TFEB is absent, this recovery fails to occur. Instead, the worms’ stem cells enter a state that closely resembles cellular senescence.

This senescent condition is characterized by several hallmark features: DNA damage, enlarged nucleoli, elevated levels of mitochondrial reactive oxygen species (ROS), and activation of inflammatory signals—all traits commonly observed in aging mammalian cells.

The study, led by Adam Antebi, director at the Max Planck Institute for Biology of Aging, presents a whole-organism model for studying senescence. This model provides a valuable tool for understanding how senescence is initiated and potentially reversed.

TFEB plays a central role in regulating cellular responses to nutrient availability, especially during fasting. Without it, worms attempt to resume growth without adequate resources, leading to a breakdown in cellular regulation and entry into a senescent-like state.

Using this model, researchers conducted genetic screens and discovered that specific growth factors—including insulin and transforming growth factor beta (TGFbeta)—are key signaling molecules disrupted by TFEB loss. These findings highlight the importance of the TFEB-TGFbeta signaling axis, which is also active during cancer diapause—a dormant state that allows cancer cells to survive chemotherapy.

Looking ahead, the team aims to use this worm model to explore potential therapies targeting senescent cells, both in the context of aging and cancer dormancy.

By Impact Labs