Discoveries in Fruit Fly Research Reveal Potential for Healthy Aging

Recent research conducted by scientists at National Taiwan University (NTU) has unveiled significant findings regarding a brain protein that may play a crucial role in promoting healthier aging. The study, published in the journal Autophagy, highlights the potential impact of manipulating a specific protein, Rab27, on lifespan and neurological health.

The research team, led by Prof. Chih-Chiang Chan, discovered that deactivating the Rab27 protein in the brains of fruit flies could lead to an extended lifespan, enhanced neuron protection, and a reduction in brain damage associated with neurodegenerative diseases, such as Parkinson's disease.

Rab27 is known for its role in assisting cells with the packaging and release of various materials. However, when the NTU researchers inhibited this protein in certain brain cells, they observed that the natural waste disposal mechanism, termed autophagy, remained operational for a longer duration. This prolonged activity allowed the brain to effectively eliminate harmful proteins, thereby aiding neuron survival and mitigating the effects of aging.

Interestingly, the study noted that levels of Rab27 typically increase during midlife. By reducing its activity at this critical stage, the researchers were able to preserve neurons in regions of the fruit fly brain that are analogous to the mammalian hippocampus and hypothalamus.

Prof. Chan explained that decreasing Rab27 activity at midlife not only supported the brain's waste recycling capabilities but also triggered beneficial signals that positively influenced the entire organism. The findings revealed that healthier neurons in the flies were linked to improved conditions in other tissues, indicating that maintaining brain health may produce widespread benefits throughout the body.

In models of Parkinson's disease, where toxic aggregates of the protein alpha-synuclein typically damage neurons, the removal of Rab27 resulted in a significant reduction of these harmful clumps. This intervention not only improved motor function in the flies but also contributed to an increased lifespan.

Although the experiments were conducted on fruit flies, the underlying biological mechanisms are highly conserved across species, including humans. The researchers believe that fine-tuning autophagy in specific cells and at appropriate times could emerge as a strategic approach to slow down aging and protect against neurodegenerative conditions in humans.

The team identified Rab27 as a key regulator that synchronizes both autophagy and protein synthesis through the TOR signaling pathway. This discovery opens new avenues for targeted therapies aimed at promoting healthy aging.

However, the researchers caution that autophagy must be carefully balanced. Insufficient autophagy can lead to toxic accumulations, while excessive autophagy can harm cells. Therefore, the timing and precision of modulation are critical, emphasizing the importance of this research for future therapeutic strategies.

For more information, refer to the publication: Chia-Heng Hsu et al., The cell autonomous and non-autonomous functions of Rab27 in longevity and neuroprotection in Drosophila, Autophagy (2025). DOI: 10.1080/15548627.2025.2541384