Fan, X., Huang, T., Wang, S., Yang, Z., Song, W., Zeng, Y., Tong, Y., Cai, Y., Yang, D., Zeng, B., Zhang, M., Ni, Q., Li, Y., Li, D., Yang, M. (2023). The adaptor protein 14-3-3zeta modulates intestinal immunity and aging in Drosophila.  J. Biol. Chem. 299(12): 105414.

FBrf0258408

Research paper

The proteins that coordinate the complex transcriptional networks of aging have not been completely documented. Protein 14-3-3zeta is an adaptor protein that coordinates signaling and transcription factor networks, but its function in aging is not fully understood. Here, we showed that the protein expression of 14-3-3zeta gradually increased during aging. High levels of 14-3-3zeta led to shortened lifespan and imbalance of intestinal immune homeostasis in Drosophila, but the decrease in 14-3-3zeta protein levels by RNAi was able to significantly promote the longevity and intestinal immune homeostasis of fruit flies. Importantly, we demonstrate that adult-onset administration of TIC10, a compound that reduces the aging-related AKT and extracellular signal-regulated kinase (ERK) signaling pathways, rescues the shortened lifespan of 14-3-3zeta-overexpressing flies. This finding suggests that 14-3-3zeta plays a critical role in regulating the aging process. Our study elucidates the role of 14-3-3zeta in natural aging and provides the rationale for subsequent 14-3-3zeta-based antiaging research.

PMC10724694 (PMC) (EuropePMC)