Metabolites related to gut bacterial metabolism, peroxisome proliferator-activated receptor-alpha activation, and insulin sensitivity are associated with physical function in functionally-limited older adults.

Identification of mechanisms underlying physical function will be important for addressing the growing challenge that health care will face with physical disablement in the expanding aging population. Therefore, the goals of the current study were to use metabolic profiling to provide insight into biologic mechanisms that may underlie physical function by examining the association between baseline and the 6-month change in serum mass spectrometry-obtained amino acids, fatty acids, and acylcarnitines with baseline and the 6-month change in muscle strength (leg press one repetition maximum divided by total lean mass, LP/Lean), lower extremity function [short physical performance battery (SPPB)], and mobility (400 m gait speed, 400-m), in response to 6 months of a combined resistance exercise and nutritional supplementation (whey protein or placebo) intervention in functionally-limited older adults (SPPB ≤ 10; 70-85 years, N = 73). Metabolites related to gut bacterial metabolism (cinnamoylglycine, phenol sulfate, p-cresol sulfate, 3-indoxyl sulfate, serotonin, N-methylproline, hydrocinnamate, dimethylglycine, trans-urocanate, valerate) that are altered in response to peroxisome proliferator-activated receptor-alpha (PPAR-α) activation (α-hydroxyisocaproate, α-hydroxyisovalerate, 2-hydroxy-3-methylvalerate, indolelactate, serotonin, 2-hydroxypalmitate, glutarylcarnitine, isobutyrylcarnitine, cinnamoylglycine) and that are related to insulin sensitivity (monounsaturated fatty acids: 5-dodecenoate, myristoleate, palmitoleate; γ-glutamylamino acids: γ-glutamylglutamine, γ-glutamylalanine, γ-glutamylmethionine, γ-glutamyltyrosine; branched-chain amino acids: leucine, isoleucine, valine) were associated with function at baseline, with the 6-month change in function or were identified in backward elimination regression predictive models. Collectively, these data suggest that gut microbial metabolism, PPAR-α activation, and insulin sensitivity may be involved in mechanisms that underlie physical function in functionally-limited older adults.

Branched chain amino acids are associated with muscle mass in functionally limited older adults.

BACKGROUND: Metabolic profiling may provide insight into biologic mechanisms related to the maintenance of muscle and fat-free mass in functionally limited older adults. The objectives of the study were to characterize the association between thigh muscle cross-sectional area (CSA) and the fat-free mass index (FFMI; total lean mass/height(2)) with the serum metabolite profile, to further identify significant metabolites as associated with markers of insulin resistance or inflammation, and to develop a metabolite predictor set representative of muscle CSA and the FFMI in functionally limited older adults. METHODS: Multivariable-adjusted linear regression was used on mass spectrometry-based metabolomic data to determine significant associations between serum metabolites with muscle CSA and the FFMI in 73 functionally limited (Short Physical Performance Battery ≤ 10) older adults (age range: 70-85 years). Significant metabolites were further examined for associations with markers of insulin resistance (homeostasis model assessment of insulin resistance) or inflammation (tumor necrosis factor-α and interleukin-6). Multivariable-adjusted stepwise regression was used to develop a metabolite predictor set representative of muscle CSA and the FFMI. RESULTS: Seven branched chain amino acid-related metabolites were found to be associated with both muscle CSA and the FFMI. Separately, two metabolites were identified as insulin resistance-associated markers of the FFMI, whereas four metabolites were identified as inflammation-associated markers of either muscle CSA or the FFMI. Stepwise models identified combinations of metabolites to explain approximately 68% of the variability inherent in muscle CSA or the FFMI. CONCLUSIONS: Collectively, we report multiple branched chain amino acids and novel inflammation-associated tryptophan metabolites as markers of muscle CSA or the FFMI in functionally limited older adults.

Efficacy of whey protein supplementation on resistance exercise-induced changes in lean mass, muscle strength, and physical function in mobility-limited older adults.

BACKGROUND: Whey protein supplementation may augment resistance exercise-induced increases in muscle strength and mass. Further studies are required to determine whether this effect extends to mobility-limited older adults. The objectives of the study were to compare the effects of whey protein concentrate (WPC) supplementation to an isocaloric control on changes in whole-body lean mass, mid-thigh muscle cross-sectional area, muscle strength, and stair-climbing performance in older mobility-limited adults in response to 6 months of resistance training (RT). METHODS: Eighty mobility-limited adults aged 70-85 years were randomized to receive WPC (40g/day) or an isocaloric control for 6 months. All participants also completed a progressive high-intensity RT intervention. Sample sizes were calculated based on the primary outcome of change in whole-body lean mass to give 80% power for a 0.05-level, two-sided test. RESULTS: Lean mass increased 1.3% and 0.6% in the WPC and control groups, respectively. Muscle cross-sectional area was increased 4.6% and 2.9% in the WPC and control groups, respectively, and muscle strength increased 16%-50% in WPC and control groups. Stair-climbing performance also improved in both groups. However, there were no statistically significant differences in the change in any of these variables between groups. CONCLUSIONS: These data suggest that WPC supplementation at this dose does not offer additional benefit to the effects of RT in mobility-limited older adults.

Systemic vascular function is associated with muscular power in older adults.

Age-associated loss of muscular strength and muscular power is a critical determinant of loss of physical function and progression to disability in older adults. In this study, we examined the association of systemic vascular function and measures of muscle strength and power in older adults. Measures of vascular endothelial function included brachial artery flow-mediated dilation (FMD) and the pulse wave amplitude reactive hyperemia index (PWA-RHI). Augmentation index (AIx) was taken as a measure of systemic vascular function related to arterial stiffness and wave reflection. Measures of muscular strength included one repetition maximum (1RM) for a bilateral leg press. Peak muscular power was measured during 5 repetitions performed as fast as possible for bilateral leg press at 40% 1RM. Muscular power was associated with brachial FMD (r = 0.43, P < 0.05), PWA-RHI (r = 0.42, P < 0.05), and AIx (r = -0.54, P < 0.05). Muscular strength was not associated with any measure of vascular function. In conclusion, systemic vascular function is associated with lower-limb muscular power but not muscular strength in older adults. Whether loss of muscular power with aging contributes to systemic vascular deconditioning or vascular dysfunction contributes to decrements in muscular power remains to be determined.

Nutrition initiatives in the context of population aging: where does the United States stand?

In 2011, the earliest segment of the baby boom generation turned 65 years of age. This event marks the beginning of a new phase of growth of the older adult population in the United States and is in line with what is referred to worldwide as "population aging." By 2030, older adults will comprise 20% of the U.S. population. With the impending increase in the older adult population, the United States is unprepared to handle the accompanying social and economic impact of growing rates of age-related diseases such as diabetes, hypertension, and cardiovascular disease. These diseases have nutritional determinants and, as such, they signify the need for effective preventive nutrition initiatives to address population aging in the United States. Comparatively, the European Union (EU) is projected to reach an older adult population of 24% by 2030. In this special article we evaluate nutrition initiatives for older adults in the United States and also examine nutrition initiatives in the European Union in search of an ideal model. However, we found that available data for EU initiatives targeted at population aging were limited. We conclude by offering the proposal of a physician-based model that establishes the primary care physician as the initiator of nutrition screening, education, referrals, and follow-up for the older adult population in the United States as a long-term goal. Apropos of the immediate future, we consider barriers that underscore the establishment of a physician-based model and suggest objectives that are attainable. Although the data are limited for the European Union, this model may serve to guide management of chronic diseases with a nutritional component in economies similar to the United States worldwide.