Our results are in line with recent, large‐scale, randomized clinical trials reporting no differences in the incidence of postoperative delirium between general and regional anesthesia.[44, 70] Notably, previous studies that have reported anesthesia‐induced cognitive deficits in aged rodents often employed longer or repeated anesthetic exposures.[71] Further investigation using varied anesthesia protocols will be essential to determine whether failure to activate ATF5‐dependent UPRmt contributes to cognitive dysfunction in the aging brain. Here, ATF5 is linked to delirium.