Scientists Conducted Experiments on Worms and Discovered a Switch to Control Aging

Worms have provided scientists with a vital clue, as they have detected what could be a switch for aging, according to Science Daily. This switch is a transcription factor called TFEB. Researchers conducted an exercise on worms with and without TFEB. In the absence of TFEB, the worm entered a senescent-like state, where cells start showing signs of aging. The symptoms of aging discovered in worms were similar to what has been observed in mammals, such as humans, when they entered this state. It made researchers speculate that a similar state of affairs regarding TFEB could be in place for humans. If the assertions are true, then it would be a breakthrough in the quest for understanding how aging begins and how it can be halted. Findings regarding this exercise have been published in the journal Nature Aging. 

The Fasting Exercise

This exercise involved long-term fasting and refeeding the worms. In the presence of TFEB, after refeeding, the worms regenerated and appeared to be rejuvenated. This exercise was also conducted in the absence of TFEB, and the results were quite different. Researchers observed that in this case, the worm's stem cells failed to recover after long-term fasting. Instead, the cell started showing features of senescence, where aging is facilitated in an organism. These features include DNA damage. Mitochondrial reactive oxygen species (ROS), the presence of inflammatory markers, and nucleolus expansion are also noted in mammalian senescence. Adam Antebi, head of the study and director at the Max Planck Institute for Biology of Ageing, claims that the model showcases how aging is triggered in an organism, and also provides clues on how it can be reversed. 

What is TFEB?

TFEB is a transcription factor that plays a crucial role in several cellular processes, like lysosomal biogenesis and autophagy, according to the National Library of Medicine. TFEB's location in a cell and its functions depend on whether the mechanistic target of rapamycin (mTOR) conducts phosphorylation on it on the surface of lysosomes. If TFEB undergoes phosphorylation, then it stays in the cytoplasm, and if not, then it travels to the nucleus to turn on specific genes. These genes regulate processes like lysosomal biogenesis and autophagy, which provide nutrients to the cell.

TFEB's Role in This Exercise

Experts believe that phosphorylation is dependent on the availability of nutrients. Hence, when TFEB does not undergo phosphorylation, it switches on genes that help the body survive in a situation where nutrients are scarce, like fasting. The processes like lysosomal biogenesis and autophagy essentially provide the cell with nutrients needed for growth functions by recycling internal resources. In the absence of TFEB, worms try to initiate growth programs in the absence of sufficient nutrients, according to SciTech. It possibly pushes the cell towards senescence.

Antebi further shares that the team conducted several genetic screenings, which showed that hormones, like insulin and TGFbeta, start behaving abnormally in the absence of TFEB. The hormones are essential for growth activities, like cell division and growth. Hence, they contribute significantly to the process of reverse aging. This dynamic between TFEB and TGFbeta has also been observed during cancer diapause, a stage where cancer cells become senescent to survive harsh conditions, like chemotherapy, and then possibly reactivate later. Researchers want to use their findings from the worm model to find further treatments that could target such cancer cells.