The ketogenic diet preserves skeletal muscle with aging in mice

The causes of the decline in skeletal muscle mass and function with age, known as sarcopenia, are poorly understood. Nutrition (calorie restriction) interventions impact many cellular processes and increase lifespan and preserve muscle mass and function with age. As we previously observed an increas...

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Bibliographic Details
Published in:Aging cell 2021-04, Vol.20 (4), p.e13322-n/a
Main Authors: Wallace, Marita A., Aguirre, Nicholas W., Marcotte, George R., Marshall, Andrea G., Baehr, Leslie M., Hughes, David C., Hamilton, Karyn L., Roberts, Megan N., Lopez‐Dominguez, Jose Alberto, Miller, Benjamin F., Ramsey, Jon J., Baar, Keith
Format: Article
Language:English
Subjects:
Adaptation
Age
Aging
Aging - physiology
Animals
Antioxidants
Antioxidants - metabolism
Biosynthesis
Diet
Diet, Ketogenic - methods
Endoplasmic reticulum
Endoplasmic Reticulum Stress - physiology
Genotype & phenotype
Growth factors
High fat diet
Inflammation
Insulin
Ketogenesis
ketogenic diet
Life span
Low carbohydrate diet
Male
Malnutrition
Metabolism
Mice
Mice, Inbred C57BL
Mitochondria
Mitochondria, Muscle - metabolism
Molecular modelling
Muscle, Skeletal - metabolism
Musculoskeletal system
Neuromuscular Junction - metabolism
Neuromuscular junctions
Nutrient deficiency
Nutrition
Organelle Biogenesis
Original Paper
Original Papers
Oxidation-Reduction
Oxidative metabolism
Oxidative stress
Oxidative Stress - physiology
Proteasome Endopeptidase Complex - metabolism
Proteasomes
Protein biosynthesis
Protein Biosynthesis - physiology
Protein turnover
Proteins
Sarcopenia
Sarcopenia - diet therapy
Sarcopenia - metabolism
Signal Transduction - physiology
Skeletal muscle
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Summary:The causes of the decline in skeletal muscle mass and function with age, known as sarcopenia, are poorly understood. Nutrition (calorie restriction) interventions impact many cellular processes and increase lifespan and preserve muscle mass and function with age. As we previously observed an increase in life span and muscle function in aging mice on a ketogenic diet (KD), we aimed to investigate the effect of a KD on the maintenance of skeletal muscle mass with age and the potential molecular mechanisms of this action. Twelve‐month‐old mice were assigned to an isocaloric control or KD until 16 or 26 months of age, at which time skeletal muscle was collected for evaluating mass, morphology, and biochemical properties. Skeletal muscle mass was significantly greater at 26 months in the gastrocnemius of mice on the KD. This result in KD mice was associated with a shift in fiber type from type IIb to IIa fibers and a range of molecular parameters including increased markers of NMJ remodeling, mitochondrial biogenesis, oxidative metabolism, and antioxidant capacity, while decreasing endoplasmic reticulum (ER) stress, protein synthesis, and proteasome activity. Overall, this study shows the effectiveness of a long‐term KD in mitigating sarcopenia. The diet preferentially preserved oxidative muscle fibers and improved mitochondrial and antioxidant capacity. These adaptations may result in a healthier cellular environment, decreasing oxidative and ER stress resulting in less protein turnover. These shifts allow mice to better maintain muscle mass and function with age. Nutrition interventions impact the preservation of skeletal muscle mass and function with age. This study demonstrated that the ketogenic diet (KD) improved skeletal muscle mass preservation with age. As muscle progresses from adult to old, individuals on a standard control (CON) diet show less reinnervation and more unfolded proteins. By contrast, individuals on a long‐term KD showed more mitochondria, greater reinnervation, more oxidative muscle fibers, and decreased translation initiation.
ISSN:1474-9718
1474-9726
DOI:10.1111/acel.13322