A key protein preserves motor ability during aging

As we age, we suffer a noticeable decline in motor ability, which affects our quality of life and independence. This can be traced to changes occurring at neuromuscular junctions, the critical points where nerve cells communicate with muscles.

The deterioration of motor ability is closely linked to the degeneration of motor synaptic terminals, where signals pass from nerves in the spine to muscles. As we age, the terminals undergo structural fragmentation, reducing the release of neurotransmitters, which is crucial for initiating muscle movements. In the end, this translates into decreased motor ability especially for strenuous movements .

Now, a study led by the group of Brian McCabe at EPFL has discovered a possible way to prevent this. The study found that the protein Trio, which regulates the structure of synapses, diminishes in aging fruit flies (Drosophila melanogaster), causing a decline in motor ability. However, increasing Trio preserves the integrity of motor synapses and delays the deterioration of motor strength. The study, published in Cell Reports, offers a promising avenue for future therapeutic strategies.

The team first found that the levels of Trio at motor synapses decline with age. Building on this the researchers focused on the effects of the protein Trio by genetically increasing its expression in aging fruit flies. This allowed them to study how the protein’s levels impacts the structural and functional stability of neuromuscular junctions.

Utilizing confocal microscopy, the researchers visualized and assessed the structural stability of neuromuscular junctions, a key factor in maintaining motor function. They followed this with biochemical assays to quantify protein levels and activity within these synapses, providing a detailed understanding of how increased Trio expression influences the biochemical landscape of aging cells.

The study showed that flies with elevated Trio levels exhibited significantly better motor ability in their middle age compared to controls. Boosting the levels of Trio maintained synaptic structures, prevented their fragmentation, and allowed the synapses to sustain high neurotransmitter release rates under intense stimuli, similar to younger flies.

The work highlights the important role of synapse integrity in maintaining motor function with age. Enhancing Trio protein can stabilize synaptic architecture, meaning that it’s possible to mitigate the decline of motor ability with aging. The findings introduce new possibilities for therapeutic interventions that target synaptic degradation in age-related motor impairments.