New Study Reveals How Brain Aging Is Driven by Protein Production Disruptions in Killifish

Researchers at Stanford University have uncovered a fundamental mechanism behind brain aging by studying the turquoise killifish, known for its rapid lifespan. Their comprehensive research points to how disruptions in the protein synthesis process, specifically at the translation elongation stage, contribute significantly to the decline in proteostasis—a vital cellular process that maintains protein homeostasis. With age, ribosomes in the brain cells of killifish tend to collide and stall, leading to reduced protein levels and the formation of harmful protein aggregates linked to neurodegenerative diseases.

The investigation focused on comparing young, adult, and old killifish, analyzing factors like mRNA, transfer RNA, amino acids, and proteins involved in protein synthesis. The team discovered that alterations in the speed of ribosome movement along mRNA molecules—resulting in collisions and stalling—play a critical role in diminishing protein quality as the organism ages.

This slowdown in translation elongation was found to be associated with a process called 'protein-transcript decoupling,' where changes in mRNA levels no longer match protein levels, especially concerning genome maintenance proteins. Such discrepancies help explain why cellular functions deteriorate during aging.

The findings emphasize that the quality control mechanisms within protein production machinery decline over time, leading to accumulation of damaged proteins and aggregation. This cascade of molecular failures appears to be a core contributor to neurodegeneration.

Future research aims to explore whether interventions targeting ribosome function and translation efficiency could restore proteostasis in brain cells and potentially delay age-related cognitive decline. The study offers promising insights into developing therapies for neurodegenerative conditions like Alzheimer's disease by focusing on the fundamental process of protein synthesis.