Trio preserves motor synapses and prolongs motor ability during aging.
Cell Rep
; 43(6): 114256, 2024 Jun 25.
Article
de En
| MEDLINE
| ID: mdl-38795343
ABSTRACT
The decline of motor ability is a hallmark feature of aging and is accompanied by degeneration of motor synaptic terminals. Consistent with this, Drosophila motor synapses undergo characteristic age-dependent structural fragmentation co-incident with diminishing motor ability. Here, we show that motor synapse levels of Trio, an evolutionarily conserved guanine nucleotide exchange factor (GEF), decline with age. We demonstrate that increasing Trio expression in adult Drosophila can abrogate age-dependent synaptic structural fragmentation, postpone the decline of motor ability, and maintain the capacity of motor synapses to sustain high-intensity neurotransmitter release. This preservative activity is conserved in transgenic human Trio, requires Trio Rac GEF function, and can also ameliorate synapse degeneration induced by depletion of miniature neurotransmission. Our results support a paradigm where the structural dissolution of motor synapses precedes and promotes motor behavioral diminishment and where intervening in this process can postpone the decline of motor function during aging.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Synapses
/
Vieillissement
Limites:
Animals
/
Humans
Langue:
En
Journal:
Cell Rep
Année:
2024
Type de document:
Article
Pays d'affiliation:
Suisse
Pays de publication:
États-Unis d'Amérique