Aging and voluntary exercise’s effects on Aβ1-42 levels, endoplasmic reticulum stress factors, and apoptosis in the hippocampus of old male rats

[Display omitted] •Voluntary exercise reduces Aβ1-42 and inhibits apoptotic pathways in old rats.•Exercise reduces ATF6, CHOP, and p-PERK proteins while increasing Bcl-2 expression.•The impact of exercise on UPR signaling pathways in the hippocampus is shown.•Findings suggest exercise as a promising therapeutic strategy for AD. Within the aging cortex, amyloid beta peptide (Aβ) is a crucial element of the senile plaques, a hallmark feature often observed in cases of Alzheimer’s disease (AD). The UPR (unfolded protein response), a cellular mechanism for protein folding, is switched on by Aβ accumulation. Endoplasmic reticulum (ER) stress has been identified as playing a role in aging and the development of neurodegenerative diseases. The exact molecular pathways leading to perishing of cells from Aβ-induced ER stress, as well as the impact of voluntary exercise on these mechanisms, are still subjects awaiting a definitive answer yet. In the current study, 18 male Wistar rats were included: 6 young rats (3 months old; 200–250 g) in the Young Control group, and 12 old rats (18 months old; 400–430 g) randomly allocated to the Old Control and Old Exercise groups. The rat cages had running wheels for them to voluntarily run on for 8 weeks. This was followed by Western blotting, immunohistochemical staining, biochemical as well as morphological analyses. Voluntary exercise reduced Aβ1-42 deposition (P