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Dietary protein is a key regulator of healthy aging in both mice and humans. In mice, reducing dietary levels of the branched-chain amino acids (BCAAs) recapitulates many of the benefits of a low protein diet; BCAA-restricted diets extend lifespan, reduce frailty, and improve metabolic health, while BCAA supplementation shortens lifespan, promotes obesity, and impairs glycemic control. Recently, high protein diets have been shown to promote cellular senescence, a hallmark of aging implicated in many age-related diseases, in the liver of mice. Here, we test the hypothesis that the effects of high protein diets on metabolic health and on cell senescence are mediated by BCAAs. We find that reducing dietary levels of BCAAs protects male and female mice from the negative metabolic consequences of both normal and high protein diets. Further, we identify tissue-specific effects of BCAAs on cellular senescence, with restriction of all three BCAAs - but not individual BCAAs - protecting from hepatic cellular senescence while potentiating cell senescence in white adipose tissue. We find that the effects of BCAAs on hepatic cellular senescence are cell-autonomous, with lower levels of BCAAs protecting cultured cells from antimycin-A induced senescence. Our results demonstrate a direct effect of a specific dietary component on a hallmark of aging and suggest that cellular senescence may be highly susceptible to dietary interventions., Competing Interests: D.W.L. has received funding from, and is a scientific advisory board member of, Aeovian Pharmaceuticals, which seeks to develop novel, selective mTOR inhibitors for the treatment of various diseases.

Background: Physical activity is protective against cardiovascular disease (CVD) and favorably improves CVD risk profile. However, more than 25 % of American adults report no participation in physical activity. Whole body electronic muscle stimulation (WB-EMS) training is a novel FDA-cleared technology which offers a time-efficient and adaptable method for physical training by simultaneously stimulating the main muscle groups using percutaneous electrical impulse transmission. Studies have demonstrated increased muscle mass, reduced fat mass, and improved functional capacity in sedentary individuals after training with WB-EMS, but studies evaluating the role of WB-EMS training on CVD risk profile are lacking., Methods: We performed a pilot randomized controlled trial in healthy adults randomized to physical training with versus without WB-EMS for one session of 20 min duration per week across 16-weeks. Study participants were asked to perform their usual activities but to abstain from any strength training during the study. During each training session, all study participants wore a specifically designed vest and arm and leg straps that were connected with electrical wires to the WB-EMS device (Miha Bodytec Gersthofen, Germany). Biphasic electrical stimulation was delivered through the vest and straps (4 s on, 4 s off) at a frequency that elicited a score of 5 or 6 on the Borg rating of perceived exertion scale from study participants when each of the following muscle groups was stimulated: thighs, buttocks, lower back, upper back, latissimus dorsi, abdomen, chest and arms. These frequencies were 'titrated' during the first 4 weeks and were then fixed at each muscle group for each participant. Individuals randomized to no WB-EMS wore the same equipment but received no electrical stimulation. Physical training sessions were provided by personal trainers certified for WB-EMS training and consisted of a fixed number of exercises and repetitions. We measured and compared several clinically important cardiovascular parameters at baseline and post-intervention., Results: Seventy-eight participants were recruited between January 2021 and March 2022 with a mean age of 35.9 ± 11.2, 61.3 % females, median BMI 24.3 (21.8, 28.1); N = 46 were randomized to intervention group and N = 32 were randomized to the control group. Eighteen (23 %) participants dropped out of the trial, including 9 participants from the EMS arm (19.6 %), and 9 participants in control arm (28.1 %). There was no significant differences in the rate of dropping out of the WB-EMS and control groups (p = 0.27). Those in the intervention group compared to controls exhibited the following changes after 16-weeks of training: waist:hip ratio (∆ -0.03 ± 0.05, p = 0.01 vs. -0.01 ± 0.0, p = 0.1), peripheral endothelial function, measured using reactive hyperemia peripheral arterial tonometry (∆: 0.02 ± 0.1, p = 0.5 vs. -0.20 ± 0.3 p = 0.05), high-sensitivity C-reactive protein (∆: 0.06 ± 0.7, p = 0.3 vs. 0.20 ± 2.3 p = 0.02), total cholesterol (∆: -1.7 ± 25.1, p = 0.3 vs. 19.2 ± 26.5, p < 0.001), high density lipoprotein (∆: 2.02 ± 6.6, p = 0.2 vs. 3.6 ± 7.5 p = 0.01) and low density lipoprotein cholesterol (∆: 0.5 ± 26.7, p = 0.4 vs. 17.1 ± 23.2, p < 0.001)., Conclusion: Once weekly physical training with WB-EMS in healthy adults resulted in either improved or stable biomarkers of cardiovascular risk, which either remained stable or worsened in those undergoing conventional training alone. Thus WB-EMS may provide an effective and time-efficient form of physical training that may be considered in those unable or unwilling to perform exercise conventionally., (Copyright © 2024. Published by Elsevier B.V.)