Cognitive function is preserved in aged mice following long-term β-hydroxy β-methylbutyrate supplementation

Michael Munroe, Ziad S. Mahmassani, Svyatoslav Dvoretskiy, Justin J. Reid, Benjamin F. Miller, Karyn Hamilton, Justin S. Rhodes, Marni D. Boppart

Research output: Contribution to journalArticlepeer-review


β-hydroxy β-methylbutyrate (HMB) is a nutritional supplement purported to enhance skeletal muscle mass and strength, as well as cognitive function in older adults. The purpose of this study was to determine the potential for long-term HMB supplementation to preserve muscle function and cognition in aged mice, as well as provide evidence of a link between vessel-associated pericyte function and outcomes. Four- (Adult/Ad) and 17 month-old (Aged/Ag) C57BL/6J mice consumed chow containing 600 mg/kg BW/day of either Ca-HMB (Ad, n=16; Ag, n=17) or Ca-Lactate (Ad, n=16; Ag, n=17) for 6 months. HMB did not prevent age-related reductions in muscle mass, strength and coordination (Age main effect, P<0.05). The rate of muscle protein synthesis decreased within the mitochondrial fraction (age main effect, P<0.05), and this decline was not prevented with HMB. Despite no change in muscle mass or function, an age-dependent reduction in active avoidance learning was attenuated with HMB (Age and HMB main effects, P<0.05). Age detrimentally impacted muscle-resident pericyte gene expression with no recovery observed with HMB, whereas no changes in brain-resident pericyte quantity or function were observed with age or HMB. The findings from this study suggest that prolonged HMB supplementation starting in adulthood may preserve cognition with age.

Original languageEnglish (US)
Pages (from-to)170-182
Number of pages13
JournalNutritional Neuroscience
Issue number3
StatePublished - Mar 3 2020


  • Aging
  • Cognition
  • HMB
  • Pericyte
  • Protein synthesis
  • Skeletal muscle

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Neuroscience(all)
  • Nutrition and Dietetics


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