Aging Differentially Affects Axonal Autophagosome Formation and Maturation

ABSTRACT Misregulation of neuronal autophagy has been implicated in age-related neurodegenerative diseases including Parkinson’s disease and Huntington’s disease. We compared autophagosome formation and maturation in primary murine neurons during development and through aging to elucidate how aging affects neuronal autophagy. We observed an age-related decrease in the rate of formation of LC3B-positive autophagosomes leading to a significant decrease in the density of autophagosomes along the axon. Next, we assessed the maturation of autophagic vesicles and identified a surprising increase in their maturation in neurons from aged mice. While we did not detect notable changes in endolysosomal content in the distal axon during aging, we found that autophagic vesicles were transported more efficiently in neurons from adult mice than in neurons from young mice. This efficient transport of autophagic vesicles in both the distal and proximal axon is maintained in neurons from aged mice and indicates that aging alone does not impair transport nor negatively impact the later stages of autophagy. However, the pronounced deficit in autophagosome biogenesis in aged neurons may contribute to a decreased capacity to clear aggregated proteins or dysfunctional organelles and thus contribute to age-related degeneration.