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

Abstract

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.

Keywords:

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

Acknowledgements

The authors would like to thank Alejandro Barranco and Christopher Moulton (Abbott Nutrition) for their advice and guidance as well as providing the Ca-HMB for this study. We also want to acknowledge undergraduate research assistants Ryan Brander and Alay Parikh for their help with data collection, and Fredrick Peelor, Jamie Laurin, and Gaia Bublitz with their help with tissue processing and isotope analysis. We would like to thank Dr Mark Band and the Functional Genomics Unit at the Roy J. Carver Biotechnology Center, for their assistance with the high throughput microfluidic qPCR. Finally, we appreciate Dr Barbara Pilas and the Flow Cytometry Center at the Roy J. Carver Biotechnology Center for their assistance with FACS.

Disclaimer statements

Contributors M.M, J.R., and M.D.B conceived and designed the research; M.M., Z.S.M., and S.D. performed experiments; M.M., Z.S.M., B.F.M, K.L.H., J.R., and M.D.B analyzed data and interpreted the results of experiments; M.M. and M.D.B prepared figures and drafted the manuscript. All authors revised and approved the final version of the manuscript.

Funding This work was supported by grants from Abbott Nutrition (US) through the Center for Nutrition, Learning, and Memory at the University of Illinois at Urbana-Champaign (Abbott CNLM ZAA68 to MDB and ZB32 to JSR).

Conflicts of interest The authors declare no conflicts of interest.

Ethics approval The research described in the manuscript is in compliance with all NIA guidelines in the treatment of animal subjects and was approved by the Institutional Animal Care and Use Committee at the University of Illinois, Urbana-Champaign.

Supplementary material

Supplemental data for this article can be accessed 10.1080/1028415X.2018.1483101.

ORCID

Benjamin F. Miller http://orcid.org/0000-0003-3283-0685

Karyn Hamilton http://orcid.org/0000-0002-6320-8824

Marni D. Boppart http://orcid.org/0000-0003-0369-6974