Researchers from the universities of Alabama, North Texas and Texas set out to explore whether a 25% BD-AcAc2 ketone ester diet would alter body composition, transcriptional regulation, the proteome and the lipidome of skeletal muscle in older mice.
“We hypothesized that the ketone ester group would remain weight stable with improvements in body composition (higher lean body mass and lower fat mass) compared to controls resulting in a healthy aging phenotype,” they wrote.
The study was supported by the National Institute on Aging of the National Institutes of Health and a Comprehensive Cancer Center Core Support Grant.
Ketones and healthy aging
The study references previous findings that ketogenic diets extend longevity and healthspan by decreasing oxidative and endoplasmic reticulum stress in mice. The resulting protein turnover in skeletal muscle, the researchers note “may allow greater maintenance of muscle mass and function with both age and disease.”
“Ketogenic diets improve or maintain metabolic function and attenuate age-related increases in adiposity and bodyweight, presumably by increasing circulating ketone concentrations in both animal models and humans,” the study authors wrote.
Because of the dietary challenges of adhering to restrictive ketogenic diets, exogenous ketones such as the BD-AcAc2 ketone ester are drawing more attention as an alternative means of inducing ketosis and the associated healthy-aging benefits.
A study from the same research group demonstrated that a diet consisting of 25% BD-AcAc2 can maintain lean body mass and induce fat mass loss in young, healthy male mice with moderate increases in circulating ketones.
“Despite extensive evidence of reductions or maintenance of body weight and adiposity, little is known about the effects BD-AcAc2 on skeletal muscle,” the researchers added.
Through a multi-omics approach, the study analyzed body weight, body composition and the skeletal muscle transcriptional, proteomic and lipidomic responses in 16 aging 72-week-old C57BL/6J mice for nine weeks.
Researchers first weighed then assigned the mice to either a ketone ester supplementation group or control and fed them ad libitum over the study period. The ketone ester diet contained 25% kcals from BD-AcAc2, which replaced 25% of carbohydrate energy in the control diet, maintaining the same fat and protein content in both groups.
“We found mice consuming a ketone ester diet remained weight stable, with no changes in fat mass or lean body mass, yet the control group increased body weight and fat mass over the course of the study,” the researchers concluded.
Energy intake and lean body mass did not differ between groups despite the difference in weight gain. The lipidomic profile was also similar between groups except for fatty acyl chains in triacylglycerol, which were 46% lower in the ketone ester group.
“Furthermore, transcriptional and proteomics data suggest a signature in skeletal muscle of ketone-treated mice consistent with markers of improved skeletal muscle regeneration, improved electron transport chain utilization and increased insulin sensitivity,” they wrote.
The study acknowledges several limitations but notes that its omics-based approach provides multiple avenues for future research and calls for more in-depth analysis with other kinds of omics studies.
“Effects of an exogenous ketone ester using multi-omics in skeletal muscle of aging C57BL/6J male mice”
Authors: Brandon M. Roberts et al.