iScience · Sep 30, 2025

Impaired axon regeneration and heightened synaptic dynamics in the injured aged mammalian cortex

By Bass C, Bharath AA, De Paola V

Aging is a key risk factor for impaired neural repair, yet its effects on axon regeneration and synaptic remodeling in the brain remain unclear. To investigate age-related repair mechanisms in neural circuits, we developed an axonal injury model in the aged (>2 years) mouse somatosensory cortex and tracked fluorescently labeled axons using in vivo multiphoton imaging. Axon degeneration rates were similar to young adults, but regeneration was markedly reduced. Six hours post-lesion, en passant boutons (EPBs)-the most common cortical synapse-showed transient increases in number and size. To assess functional consequences, we used a recurrent neural network model to simulate memory dynamics, revealing distinct changes compared to young adults. Our results suggest that increased synaptic turnover in the aged brain may facilitate partial recovery from injury through synaptic re-wiring, highlighting potential mechanisms supporting neural adaptation in aging.

doi.org/10.1016/j.isci.2025.113665Open accessPubMed 41244571Mechanisms