From bedside to battlefield: intersection of ketone body mechanisms in geroscience with military resilience
- PDF / 536,701 Bytes
- 11 Pages / 547.087 x 737.008 pts Page_size
- 35 Downloads / 211 Views
REVIEW
From bedside to battlefield: intersection of ketone body mechanisms in geroscience with military resilience Brianna J. Stubbs & Andrew P. Koutnik & Jeff S. Volek & John C. Newman
Received: 5 August 2020 / Accepted: 22 September 2020 # The Author(s) 2020
Abstract Ketone bodies are endogenous metabolites that are linked to multiple mechanisms of aging and resilience. They are produced by the body when glucose availability is low, including during fasting and dietary carbohydrate restriction, but also can be consumed as exogenous ketone compounds. Along with supplying energy to peripheral tissues such as brain, heart, and skeletal muscle, they increasingly are understood to have drug-like protein binding activities that regulate inflammation, epigenetics, and other cellular processes. While these energy and signaling mechanisms of ketone bodies are currently being studied in a variety of agingrelated diseases such as Alzheimer’s disease and type 2 diabetes mellitus, they may also be relevant to military service members undergoing stressors that mimic or Brianna J. Stubbs and Andrew P. Koutnik contributed equally to this work. B. J. Stubbs : J. C. Newman Buck Institute for Research on Aging, Novato, CA, USA A. P. Koutnik Institute for Human and Machine Cognition, Pensacola, FL, USA A. P. Koutnik Department of Molecular Pharmacology and Physiology, USF, Tampa, FL, USA J. S. Volek Department of Human Sciences, Ohio State University, Columbus, OH, USA J. C. Newman (*) Division of Geriatrics, UCSF, San Francisco, CA, USA e-mail: [email protected]
accelerate aging pathways, particularly traumatic brain injury and muscle rehabilitation and recovery. Here we summarize the biology of ketone bodies relevant to resilience and rehabilitation, strategies for translational use of ketone bodies, and current clinical investigations in this area. Keywords Metabolism . Ketone bodies . Aging . Geroscience . TBI . Sarcopenia Abbreviations AcAc Acetoacetate BHB Beta-hydroxybutyrate (aka 3hydroxybutyrate) MCTs Medium chain triglycerides NLRP3 NOD-, LRR- and pyrin domain-containing protein 3 T2DM Type 2 diabetes mellitus TBI Traumatic brain injury
Endogenous ketone production and metabolism Ketone bodies are endogenous metabolites that have been implicated in modulation of multiple pathways relevant to aging and aging-related resilience [1]. A growing catalog of direct molecular actions support their roles in geroprotective pathways, as does circumstantial evidence from their induction in aging-relevant physiological settings such as fasting, dietary restriction, and exercise [2–4]. The increased physical and emotional
GeroScience
stress experienced by military service members during their career may act to accelerate the aging process in these individuals [5, 6]. Furthermore, the military population has an increased risk of sustaining injuries and accumulating complex co-morbidities that could go on to contribute to physical disability or cognitive decline [7–10]. Therefore, there may be significant areas of applica
Data Loading...
