Serum metabolomic adaptations following a 12-week high-intensity interval training combined to citrulline supplementation in obese older adults.

Physical activity and nutrition play important roles in preventing adverse health outcomes that accompany aging. It has been shown that high-intensity interval training (HIIT) combined with citrulline (CIT) supplementation can improve physical and functional capacities. The aim of this study was to evaluate serum metabolites following a 12-week HIIT combined or not with CIT in obese older adults, and to correlate the metabolic changes with clinico-biological parameters changes. Eighty-six obese older adults completed a 12-week HIIT program combined with a 10 g daily supplementation of either CIT or placebo (PLA) during a double-blinded randomized interventional trial. Only participants with blood samples at T0 (before the intervention) and/or T12 (after the intervention) were included in our sub-analysis (HIIT-PLA-T0: n = 44 and HIIT-PLA-T12: n = 28; HIIT-CIT-T0: n = 39 and HIIT-CIT-T12: n = 42). Serum samples were analyzed by different liquid or gas phase chromatography methods coupled to mass spectrometry. Among the identified metabolites, 44 changed significantly following the 12-week intervention (Time effect), and 10 of them were more affected when HIIT was combined with CIT (Time × Supp effect). Arginine increased significantly due to the 12-week intervention. Correlation analyses demonstrated that decreased triglyceride (TG) (16:1/18:1/16:0) and aspartic acid significantly correlated with a reduction of adiposity-related parameters (fat mass, leg lean mass, leptin, total triglycerides and low-density lipoprotein). Arginine, TG (16:1/18:1/16:0) and aspartic acid might constitute biomarkers of cardiometabolic health and adiposity. Further studies are needed to confirm these associations and understand the underlying mechanisms.Highlights A 12-week intervention involving high-intensity interval training (HIIT) with or without citrulline (CIT) supplementation induced adaptations in the serum metabolome of obese older adults through significant changes in 44 metabolites.Changes in 23 metabolites were observed when a CIT supplementation was administered along with a 12-week HIIT intervention.TG (16:1/18:1/16:0) correlated with several adiposity parameters including leptin, triglycerides, legs lean mass.Aspartic acid correlated with several adiposity parameters including leptin, LDL cholesterol as well as android, arms and trunk fat mass.

Obesity and ageing: Two sides of the same coin.

Conditions and comorbidities of obesity mirror those of ageing and age-related diseases. Obesity and ageing share a similar spectrum of phenotypes such as compromised genomic integrity, impaired mitochondrial function, accumulation of intracellular macromolecules, weakened immunity, shifts in tissue and body composition, and enhanced systemic inflammation. Moreover, it has been shown that obesity reduces life expectancy by 5.8 years in men and 7.1 years in women after the age of 40. Shorter life expectancy could be because obesity holistically accelerates ageing at multiple levels. Besides jeopardizing nuclear DNA and mitochondrial DNA integrity, obesity modifies the DNA methylation pattern, which is associated with epigenetic ageing in different tissues. Additionally, other signs of ageing are seen in individuals with obesity including telomere shortening, systemic inflammation, and functional declines. This review aims to show how obesity and ageing are "two sides of the same coin" through discussing how obesity predisposes an individual to age-related conditions, illness, and disease. We will further demonstrate how the mechanisms that perpetuate the early-onset of chronic diseases in obesity parallel those of ageing.

Mitochondrial Content, but Not Function, Is Altered With a Multimodal Resistance Training Protocol and Adequate Protein Intake in Leucine-Supplemented Pre/Frail Women.

Background: Frailty is a clinical condition associated with loss of muscle mass and strength (sarcopenia). Mitochondria are centrally implicated in frailty and sarcopenia. Leucine (Leu) can alter mitochondrial content in myocytes, while resistance training (RT) is the strongest stimulus to counteract sarcopenia and may enhance mitochondrial biogenesis. Objective: We determined the effects of Leu supplementation and RT on mitochondrial content and function in pre/frail elderly women in a randomized double-blinded placebo-controlled study. Methods: Nineteen pre/frail elderly women (77.5 ± 1.3 y, BMI: 25.1 ± 0.9 kg/m2), based on the Frailty Phenotype, underwent 3-months of RT 3×/week with protein-optimized diet and were randomized to 7.5 g/d of Leu supplementation or placebo alanine (Ala). Pre/post-intervention mitochondrial respiration, reactive oxygen species (ROS) production, calcium retention capacity (CRC), time to permeability transition pore (mPTP) opening, mitochondrial voltage-dependent anion channel (VDAC) protein content, leg press 1-repetition maximum (1RM), and 6-min walk test (6MWT) were measured. Results: No time, supplementation, or interaction effects were observed for respiration, ROS, time to mPTP opening, and CRC. VDAC levels significantly increased in the Leu group post-intervention (p = 0.012). Both groups significantly increased leg press 1RM and 6MWT, with no effect of supplementation. Discussion: Leu supplementation with 3 months of RT increased mitochondrial content. Future studies should investigate if there is an increase in mitochondrial turnover or a shift in quality control (mitophagy) in leucine supplemented pre/frail elderly women who undergo 12 weeks of RT. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT01922167.

Improved Human Muscle Biopsy Method To Study Neuromuscular Junction Structure and Functions with Aging.

Reduced mobility and physical independence of elders has emerged as a major clinical and public health priority with extended life expectancy. The impact of the neuromuscular function on muscle activity and properties has emerged as a critical factor influencing the progress and outcome of muscle changes with aging. However, very little is known about the neuromuscular junctions (NMJs) in humans, in part due to technical constraints limiting the access to healthy, fresh neuromuscular tissue. Here, we describe a method, called Biopsy using Electrostimulation for Enhanced NMJ Sampling (BeeNMJs) that improves the outcome of muscle biopsies. We used local cutaneous stimulation to identify the area enriched with NMJs for each participant at the right Vastus lateralis (VL). The needle biopsy was then performed in proximity of that point. The BeeNMJs procedure was safe for the participants. We observed NMJs in 53.3% of biopsies in comparison with only 16.7% using the traditional method. Furthermore, we observed an average of 30.13 NMJs per sample compared to only 2.33 for the traditional method. Importantly, high-quality neuromuscular material was obtained whereby pre-, postsynaptic, and glial elements were routinely labeled, simultaneously with myosin heavy chain type I. The BeeNMJs approach will facilitate studies of NMJs, particularly in human disease or aging process.

Leucine Supplementation Does Not Alter Insulin Sensitivity in Prefrail and Frail Older Women following a Resistance Training Protocol.

BACKGROUND: Frailty is a clinical condition associated with loss of muscle mass and strength (sarcopenia). Although sarcopenia has multifactorial causes, it might be partly attributed to a blunted response to anabolic stimuli. Leucine acutely increases muscle protein synthesis, and resistance training (RT) is the strongest stimuli to counteract sarcopenia and was recently shown to improve insulin sensitivity (IS) in frail older women. Discrepancies exist regarding whether chronic supplementation of leucine in conjunction with RT can improve muscle mass and IS. OBJECTIVE: The aim of this double-blinded placebo-controlled study was to determine the effects of leucine supplementation and RT on IS in prefrail and frail older women. METHODS: Using the Fried criteria, 19 nondiabetic prefrail (1-2 criteria) and frail (≥3 criteria) older women (77.5 ± 1.3 y; body mass index (kg/m2): 25.1 ± 0.9) underwent a 3-mo intervention of RT 3 times/wk with protein-optimized diet of 1.2 g·kg-1·d-1 and 7.5 g·d-1 of l-leucine supplementation compared with placebo l-alanine. Pre-/postintervention primary outcomes were fasting plasma glucose, serum insulin, and 4-h responses to a standard meal of complete liquid formula. Secondary outcomes of resting energy expenditure using indirect calorimetry and body composition using dual-energy X-ray absorptiometry were obtained. Paired t tests analyzed pooled data, and 2-factor repeated-measures ANOVA determined supplementation, training, and interaction effects. RESULTS: No significant time, group, or interaction effects were observed for postprandial areas under the curve of serum insulin or plasma glucose or for resting energy expenditure in l-leucine compared with l-alanine. Total lean body mass increased and percentage body fat decreased significantly for both groups postintervention (0.76 ± 0.13 and -0.92 ± 0.33 kg, respectively; time effect: P < 0.01). CONCLUSIONS: IS was not affected by RT and leucine supplementation in nondiabetic prefrail and frail older women. Therefore, leucine supplementation does not appear to influence IS under these conditions. This trial was registered at clinicaltrials.gov as NCT01922167.

SYNERGIC TRIAL (SYNchronizing Exercises, Remedies in Gait and Cognition) a multi-Centre randomized controlled double blind trial to improve gait and cognition in mild cognitive impairment.

BACKGROUND: Physical exercise, cognitive training, and vitamin D are low cost interventions that have the potential to enhance cognitive function and mobility in older adults, especially in pre-dementia states such as Mild Cognitive Impairment (MCI). Aerobic and progressive resistance exercises have benefits to cognitive performance, though evidence is somewhat inconsistent. We postulate that combined aerobic exercise (AE) and progressive resistance training (RT) (combined exercise) will have a better effect on cognition than a balance and toning control (BAT) intervention in older adults with MCI. We also expect that adding cognitive training and vitamin D supplementation to the combined exercise, as a multimodal intervention, will have synergistic efficacy. METHODS: The SYNERGIC trial (SYNchronizing Exercises, Remedies in GaIt and Cognition) is a multi-site, double-blinded, five-arm, controlled trial that assesses the potential synergic effect of combined AE and RT on cognition and mobility, with and without cognitive training and vitamin D supplementation in older adults with MCI. Two-hundred participants with MCI aged 60 to 85 years old will be randomized to one of five arms, four of which include combined exercise plus combinations of dual-task cognitive training (real vs. sham) and vitamin D supplementation (3 × 10,000 IU/wk. vs. placebo) in a quasi-factorial design, and one arm which receives all control interventions. The primary outcome measure is the ADAS-Cog (13 and plus modalities) measured at baseline and at 6 months of follow-up. Secondary outcomes include neuroimaging, neuro-cognitive performance, gait and mobility performance, and serum biomarkers of inflammation (C reactive protein and interleukin 6), neuroplasticity (brain-derived neurotropic factor), endothelial markers (vascular endothelial growth factor 1), and vitamin D serum levels. DISCUSSION: The SYNERGIC Trial will establish the efficacy and feasibility of a multimodal intervention to improve cognitive performance and mobility outcomes in MCI. These interventions may contribute to new approaches to stabilize and reverse cognitive-mobility decline in older individuals with MCI. TRIAL REGISTRATION: Identifier: NCT02808676. https://www.clinicaltrials.gov/ct2/show/NCT02808676 .

The elderly patient with cancer: a holistic view.

The elderly cancer patient (ECP) population is a heterogeneous group, ranging from competent, active, and fit individuals to those who are frail and cognitively impaired. A continuum exists from an increased vulnerability to stressors that results from the usual decreases in physiologic reserves (=aging) to the deregulation of multiple physiologic systems (=frailty). The ability or inability of carrying out activities of daily living is both a cause and an effect of frailty and may exacerbate the clinical manifestations of comorbidities. Cachexia is one of the most important comorbid conditions in ECPs, which can directly impair their quality of life, their ability to tolerate tumor-directed treatments, and their ability to respond to rehabilitation. Gait speed, handgrip strength, and cognitive tests along with simple laboratory tests to rule out the presence of increased inflammatory state and/or a particular hormonal deficiency may guide interventions and allow for monitoring of clinical outcomes over time. An organized social network, collaborative support from the team of caregivers and sufficient home care services comprise a comprehensive care approach that guarantees successful treatment outcomes for the ECP population.

Increase in the thermic effect of food in women by adrenergic amines extracted from citrus aurantium.

OBJECTIVE: To compare the thermic response to a meal between men and women of varied body composition and to determine whether adrenergic amines extracted from citrus aurantium (CA) induce an increase in metabolic rate and enhance the thermic response to the meal. RESEARCH METHODS AND PROCEDURES: In 30 healthy weight-stable subjects (17 women, 13 men; BMI: 20 to 42 kg/m2), body composition was determined by bioimpedance analysis followed by resting energy expenditure for 20 minutes, and the thermic effect of food (TEF) of a 1.7-MJ, 30-gram protein meal was determined intermittently for 300 minutes by indirect calorimetry. In a subset of 22 subjects, the TEFs of CA alone and when added to the same 1.7-MJ meal were determined. Blood pressure and pulse before and throughout the studies and catecholamine excretion were determined. RESULTS: TEF was significantly lower in women than men (152 +/- 7 vs. 190 +/- 12 kJ and 8.8 +/- 0.4% vs. 11.0 +/- 0.7% of meal), independently of age and magnitude of adiposity. The thermic response to CA alone was higher in men, but, when added to the meal, CA increased TEF only in women and to values no longer different from men. CA had no effect on blood pressure and pulse rate but increased epinephrine excretion by 2.4-fold. DISCUSSION: A 20% lower TEF in women suggests a diminished sympathetic nervous system response to meals, because with CA, TEF increased by 29% only in women. However, this acute response may not translate into a chronic effect or a clinically significant weight loss over time.