Changes in adropin levels in brain and peripheral tissues with aging.

Adropin is a bioactive peptide found in the brain and various peripheral tissues. Evidence suggests that aging significantly decreases brain adropin levels, and interventions that elevate adropin may help alleviate age-related neurological disorders such as ischemic stroke and cognitive decline. However, the impact of aging on peripheral tissue adropin levels and its relationship with the neural recognition molecule NB-3/contactin-6 in the brain remains unclear. In this study, we quantified adropin using immunoblotting in brain and peripheral tissues (liver, lung, kidney, spleen, ileum, colon) from young (8-10 weeks) and aged (18-20 months) male mice. Results indicated a significant decrease in brain adropin levels in aged mice, while peripheral tissues showed no significant changes compared to young controls. Additionally, levels of NB-3/contactin-6, a potential adropin receptor and Notch1 ligand, were lower in aged brains. Co-immunoprecipitation demonstrated that adropin physically associates with brain NB-3. Notably, the age-related reduction in brain adropin correlates with increased oxidative stress markers (gp91phox and 4-hydroxynonenal). We provide the first evidence that aging is linked to a concurrent loss of adropin and NB-3 in the brain but not in peripheral tissues. Interventions to maintain brain adropin levels could help mitigate the brain's aging process and alleviate age-related neurological dysfunction.