title: Impact of β-hydroxy β-methylbutyrate (HMB) on age-related functional deficits in mice.
abstract: β-Hydroxy β-methylbutyrate (HMB) is a metabolite of the essential amino acid leucine. Recent studies demonstrate a decline in plasma HMB concentrations in humans across the lifespan, and HMB supplementation may be able to preserve muscle mass and strength in older adults. However, the impact of HMB supplementation on hippocampal neurogenesis and cognition remains largely unexplored. The purpose of this study was to simultaneously evaluate the impact of HMB on muscle strength, neurogenesis and cognition in young and aged mice. In addition, we evaluated the influence of HMB on muscle-resident mesenchymal stem/stromal cell (Sca-1+CD45-; mMSC) function to address these cells potential to regulate physiological outcomes. Three month-old (n=20) and 24 month-old (n=18) female C57BL/6 mice were provided with either Ca-HMB or Ca-Lactate in a sucrose solution twice per day for 5.5weeks at a dose of 450mg/kg body weight. Significant decreases in relative peak and mean force, balance, and neurogenesis were observed in aged mice compared to young (age main effects, p≤0.05). Short-term HMB supplementation did not alter activity, balance, neurogenesis, or cognitive function in young or aged mice, yet HMB preserved relative peak force in aged mice. mMSC gene expression was significantly reduced with age, but HMB supplementation was able to recover expression of select growth factors known to stimulate muscle repair (HGF, LIF). Overall, our findings demonstrate that while short-term HMB supplementation does not appear to affect neurogenesis or cognitive function in young or aged mice, HMB may maintain muscle strength in aged mice in a manner dependent on mMSC function.
authors.affiliation: Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Munroe
authors.affiliation: Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Yair
authors.initials: Y
authors.lastname: Pincu
authors.affiliation: Department of Psychology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Merritt
authors.affiliation: Department of Psychology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Cobert
authors.affiliation: Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Brander
authors.affiliation: Division of Biomedical Sciences, Carle Hospital, Urbana, IL 61801, USA.
authors.forename: Tor
authors.initials: T
authors.lastname: Jensen
authors.affiliation: Department of Psychology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Rhodes
authors.affiliation: Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: mboppart@illinois.edu.
authors.forename: Marni D
authors.initials: MD
authors.lastname: Boppart
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D019587:Dietary Supplements; D005260:Female; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053580:Muscle Strength / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D059467:Transcriptome; D014631:Valerates / Q000494:pharmacology*
chemical_list: D014631:Valerates; C004961:beta-hydroxyisovaleric acid
keywords: Aging; Cognition; Mesenchymal stem cells; Neurogenesis; Nutrition