Constitutive macroautophagy involved in the turnover of defective long-lived 
proteins and organelles is crucial for neuronal homeostasis. We hypothesized 
that macroautophagic dysregulation in selective brain regions was associated 
with memory impairment in aged mice. We used the single-trial object recognition 
test to measure short-term memory in 18 aged mice compared to 22 young mice and 
employed immunohistochemistry to assess cellular distribution of proteins 
involved in the selective degradation of ubiquitinated proteins via 
macroautophagy. Values of the discrimination ratio (DR, a measure of short-term 
recognition memory performance) in aged mice were significantly lower than those 
in young mice (median, 0.54 vs. 0.67; p = 0.005, U test). Almost exclusively in 
aged mice, there were clusters of puncta immunoreactive for 
microtubule-associated protein 1 light chain 3 (LC3), ubiquitin- and LC3-binding 
protein p62, and ubiquitin in neuronal processes predominantly in the 
hippocampal formation, olfactory bulb/tubercle, and cerebellar cortex. The 
hippocampal burden of clustered puncta immunoreactive for LC3 and p62 exhibited 
inverse linear correlations with DR in aged mice (ρ = -0.48 and -0.55, p = 0.044 
and 0.018, respectively, Spearman's rank correlation). These findings suggest 
that increased accumulation of autophagosomes within neuronal processes in 
selective brain regions is characteristic of aging. The dysregulation of 
macroautophagy can adversely affect the turnover of aggregate-prone proteins and 
defective organelles, which may contribute to memory impairment in aged mice.