Comparative organ-wide analysis of age-related N-glycan alterations in mice reveals a link to lysosomal glycosidases

Glycosylation is an important post-translational modification, and glycan alterations reflect physiological and pathological states. However, whether common age-associated glycan changes occur across organs remains unclear. Here, we analyzed protein-bound N-glycans in serum, brain, lung, heart, liver, skeletal muscle, and kidney to identify aging-related alterations shared across tissues. Although glycan profiles were strongly organ-specific, age-dependent changes were observed in each organ. The proportion of paucimannose glycans increased in multiple organs and showed a significant positive correlation with age. The lysosomal glycosidases Hexa/Hexb, which are potentially involved in paucimannose glycan generation, were upregulated in the lung during aging. In cultured cells, elevated expression of these enzymes and increased paucimannose glycans were observed in senescent cells. These findings suggest that paucimannose glycans are closely associated with aging, although a causal role of HEXA/HEXB upregulation in their formation was not directly tested; they may also serve as indicators of cellular and organ aging.