Effects of β-hydroxy-β-methylbutyrate (HMB) supplementation on biomarkers for cognitive function and electrophysiological processes in aging

β-hydroxy-β-methylbutyric acid (HMB) is a leucine metabolite known for increasing muscle mass; however, recent studies have also shown it to have cognitive benefits, particularly with aging. The current study set out to explore the potential mechanism by which ??? supplementation mediates its beneficial cognitive effects. ??? treatment was found to increase hippocampal mammalian target of rapamycin (mTOR) activity in both young and aged rats, while also increasing mTOR medial prefrontal cortical (mPFC) activity in aged rats. Cyclic adenosine monophosphate response element-binding protein (CREB) was found to exhibit an age-dependent decrease in both the hippocampus and mPFC, as previously established, with HMB treatment significantly increasing CREB activity in only the mPFC of aged rats. These observed changes in mTOR and CREB did not translate to significant effects on long-termpotentiation in either brain region, suggesting that HMB’s cognitive effects are associated with changes in other mechanisms. One leading candidate in light of the pattern of mTOR/CREB activation is an ???-induced decrease in oxidative stress during aging. This, along with the fact that decreased oxidative stress facilitates learning and has been reported to occur following ??? treatment, further suggests an alternative mechanism for ???‘s potential to reduce aging-related cognitive decline.