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Acute ingestion of a ketone monoester, whey protein, or their co-ingestion in the overnight postabsorptive state elicit a similar stimulation of myofibrillar protein synthesis rates in young males: a double-blind randomized trial.
Hannaian, SJ, Lov, J, Hawley, SE, Dargegen, M, Malenda, D, Gritsas, A, Gouspillou, G, Morais, JA, Churchward-Venne, TA
The American journal of clinical nutrition. 2024;(3):716-729
Abstract
BACKGROUND Ketone bodies may have anabolic effects in skeletal muscle via their capacity to stimulate protein synthesis. Whether orally ingested exogenous ketones can stimulate postprandial myofibrillar protein synthesis (MyoPS) rates with and without dietary protein co-ingestion is unknown. OBJECTIVES This study aimed to evaluate the effects of ketone monoester intake and elevated blood β-hydroxybutyrate (β-OHB) concentration, with and without dietary protein co-ingestion, on postprandial MyoPS rates and mechanistic target of rapamycin complex 1 (mTORC1) pathway signaling. METHODS In a randomized, double-blind, parallel group design, 36 recreationally active healthy young males (age: 24.2 ± 4.1 y; body fat: 20.9% ± 5.8%; body mass index: 23.4 ± 2 kg/m2) received a primed continuous infusion of L-[ring-2H5]-phenylalanine and ingested one of the following: 1) the ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KET), 2) 10 g whey protein (PRO), or 3) the combination of both (KET+PRO). Blood and muscle biopsy samples were collected during basal and postprandial (300 min) conditions to assess β-OHB, glucose, insulin, and amino acid concentrations, MyoPS rates, and mTORC1 pathway signaling. RESULTS Capillary blood β-OHB concentration increased similarly during postprandial conditions in KET and KET+PRO, with both being greater than PRO from 30 to 180 min (treatment × time interaction: P < 0.001). Postprandial plasma leucine and essential amino acid (EAA) incremental area under the curve (iAUC) over 300 min was greater (treatment: both P < 0.001) in KET+PRO compared with PRO and KET. KET, PRO, and KET+PRO stimulated postprandial MyoPS rates (0-300 min) higher than basal conditions [absolute change: 0.020%/h; (95% CI: 0.013, 0.027%/h), 0.014%/h (95% CI: 0.009, 0.019%/h), 0.019%/h (95% CI: 0.014, 0.024%/h), respectively (time: P < 0.001)], with no difference between treatments (treatment: P = 0.383) or treatment × time interaction (interaction: P = 0.245). mTORC1 pathway signaling responses did not differ between treatments (all P > 0.05). CONCLUSIONS Acute oral intake of a ketone monoester, 10 g whey protein, or their co-ingestion in the overnight postabsorptive state elicit a similar stimulation of postprandial MyoPS rates in healthy young males. This trial was registered at clinicaltrials.gov as NCT04565444 (https://clinicaltrials.gov/study/NCT04565444).
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Impact of 14 Days of Bed Rest in Older Adults and an Exercise Countermeasure on Body Composition, Muscle Strength, and Cardiovascular Function: Canadian Space Agency Standard Measures.
Hajj-Boutros, G, Sonjak, V, Faust, A, Hedge, E, Mastrandrea, C, Lagacé, JC, St-Martin, P, Naz Divsalar, D, Sadeghian, F, Chevalier, S, et al
Gerontology. 2023;(11):1284-1294
Abstract
INTRODUCTION Head-down bed rest (HDBR) has long been used as an analog to microgravity, and it also enables studying the changes occurring with aging. Exercise is the most effective countermeasure for the deleterious effects of inactivity. The aim of this study was to investigate the efficacy of an exercise countermeasure in healthy older participants on attenuating musculoskeletal deconditioning, cardiovascular fitness level, and muscle strength during 14 days of HDBR as part of the standard measures of the Canadian Space Agency. METHODS Twenty-three participants (12 males and 11 females), aged 55-65 years, were admitted for a 26-day inpatient stay at the McGill University Health Centre. After 5 days of baseline assessment tests, they underwent 14 days of continuous HDBR followed by 7 days of recovery with repeated tests. Participants were randomized to passive physiotherapy or an exercise countermeasure during the HDBR period consisting of 3 sessions per day of either high-intensity interval training (HIIT) or low-intensity cycling or strength exercises for the lower and upper body. Peak aerobic power (V̇O2peak) was determined using indirect calorimetry. Body composition was assessed by dual-energy X-ray absorptiometry, and several muscle group strengths were evaluated using an adjustable chair dynamometer. A vertical jump was used to assess whole-body power output, and a tilt test was used to measure cardiovascular and orthostatic challenges. Additionally, changes in various blood parameters were measured as well as the effects of exercise countermeasure on these measurements. RESULTS There were no differences at baseline in main characteristics between the control and exercise groups. The exercise group maintained V̇O2peak levels similar to baseline, whereas it decreased in the control group following 14 days of HDBR. Body weight significantly decreased in both groups. Total and leg lean masses decreased in both groups. However, total body fat mass decreased only in the exercise group. Isometric and isokinetic knee extension muscle strength were significantly reduced in both groups. Peak velocity, flight height, and flight time were significantly reduced in both groups with HDBR. CONCLUSION In this first Canadian HDBR study in older adults, an exercise countermeasure helped maintain aerobic fitness and lean body mass without affecting the reduction of knee extension strength. However, it was ineffective in protecting against orthostatic intolerance. These results support HIIT as a promising approach to preserve astronaut health and functioning during space missions, and to prevent deconditioning as a result of hospitalization in older adults.
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Predictive Strategies to Reduce the Risk of Rehospitalization with a Focus on Frail Older Adults: A Narrative Review.
Bag Soytas, R, Levinoff, EJ, Smith, L, Doventas, A, Morais, JA, Veronese, N, Soysal, P
Epidemiologia (Basel, Switzerland). 2023;(4):382-407
Abstract
Frailty is a geriatric syndrome that has physical, cognitive, psychological, social, and environmental components and is characterized by a decrease in physiological reserves. Frailty is associated with several adverse health outcomes such as an increase in rehospitalization rates, falls, delirium, incontinence, dependency on daily living activities, morbidity, and mortality. Older adults may become frailer with each hospitalization; thus, it is beneficial to develop and implement preventive strategies. The present review aims to highlight the epidemiological importance of frailty in rehospitalization and to compile predictive strategies and related interventions to prevent hospitalizations. Firstly, it is important to identify pre-frail and frail older adults using an instrument with high validity and reliability, which can be a practically applicable screening tool. Comprehensive geriatric assessment-based care is an important strategy known to reduce morbidity, mortality, and rehospitalization in older adults and aims to meet the needs of frail patients with a multidisciplinary approach and intervention that includes physiological, psychological, and social domains. Moreover, effective multimorbidity management, physical activity, nutritional support, preventing cognitive frailty, avoiding polypharmacy and anticholinergic drug burden, immunization, social support, and reducing the caregiver burden are other recommended predictive strategies to prevent post-discharge rehospitalization in frail older adults.
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Serum metabolomic adaptations following a 12-week high-intensity interval training combined to citrulline supplementation in obese older adults.
Youssef, L, Durand, S, Aprahamian, F, Lefevre, D, Bourgin, M, Maiuri, MC, Dulac, M, Hajj-Boutros, G, Marcangeli, V, Buckinx, F, et al
European journal of sport science. 2023;(11):2157-2169
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Abstract
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.
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Pre-Dementia Stages and Incident Dementia in the NuAge Study.
Beauchet, O, Sekhon, H, Launay, CP, Gaudreau, P, Morais, JA, Allali, G
Journal of Alzheimer's disease : JAD. 2021;(4):1465-1470
Abstract
BACKGROUND Motoric cognitive risk syndrome (MCR) and mild cognitive impairment (MCI) are two pre-dementia stages with an overlap, which may influence the risk for dementia. OBJECTIVE The study aims to examine the association of MCR, MCI, and their combination with incident dementia in Quebec community-dwelling older adults. METHODS 1,063 older adults (i.e., ≥65) were selected from a population-based observational cohort study known as the "Nutrition as a determinant of successful aging: The Quebec longitudinal study" (NuAge). Participants were separated into four groups at the baseline assessment: those without MCR and MCI (i.e., cognitively healthy individual; CHI), those with MCR alone, those with MCI alone, and those with MCR plus MCI. Incident dementia was recorded at each annual visit during a 3-year follow-up. RESULTS The prevalence of CHI was 87.2%, MCR 3.0%, MCI 8.8%, and MCR plus MCI 0.9%. The overall incidence of dementia was 2.4% and was significantly associated with MCR alone (Odd Ratio (OR) = 5.00 with 95% Confidence interval (CI) = [1.01;24.59] and p = 0.049), MCI alone (OR = 6.04 with 95% CI = [2.36;15.47] and p≤0.001), and the combination of MCR and MCI (OR = 25.75 with 95% CI = [5.32;124.66] and p≤0.001). CONCLUSION Combining MCR and MCI increased the risk for incident dementia. These results also demonstrated that this combination is a better predictor of dementia than MCI or MCR alone.
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Motoric cognitive risk syndrome and incident dementia in older adults from the Québec NuAge cohort.
Beauchet, O, Sekhon, H, Cooper-Brown, L, Launay, CP, Gaudreau, P, Morais, JA, Allali, G
Age and ageing. 2021;(3):969-973
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Abstract
BACKGROUND The co-occurrence of slow walking speed and subjective cognitive complaint (SCC) in non-demented individuals defines motoric cognitive risk syndrome (MCR), which is a pre-dementia stage. There is no information on the association between MCR and incident dementia in Québec's older population. OBJECTIVE The study aims to examine the association of MCR and its individual components (i.e. SCC and slow walking speed) with incident dementia in community-dwelling older adults living in the province of Québec (Canada). DESIGN Québec older people population-based observational cohort study with 3 years of follow-up. SETTING Community dwellings. SUBJECTS A subset of participants (n = 1,098) in 'Nutrition as a determinant of successful aging: The Québec longitudinal study' (NuAge). METHODS At baseline, participants with MCR were identified. Incident dementia was measured at annual follow-up visits using the Modified Mini-Mental State (≤79/100) test and Instrumental Activity Daily Living scale (≤6/8) score values. RESULTS The prevalence of MCR was 4.2% at baseline and the overall incidence of dementia was 3.6%. MCR (Hazard Ratio (HR) = 5.18, with 95% confidence interval (CI) = [2.43-11.03] and P ≤ 0.001) and SCC alone (HR = 2.54, with 95% CI = [1.33-4.85] and P = 0.005) were associated with incident dementia, but slow walking speed was not (HR = 0.81, with 95%CI = [0.25-2.63] and P = 0.736). CONCLUSIONS MCR and SCC are associated with incident dementia in NuAge study participants.
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Effects of slow- v. fast-digested protein supplementation combined with mixed power training on muscle function and functional capacities in older men.
Dulac, MC, Pion, CH, Lemieux, FC, Pinheiro Carvalho, L, El Hajj Boutros, G, Bélanger, M, Gaudreau, P, Chevalier, S, Morais, JA, Noirez, P, et al
The British journal of nutrition. 2021;(9):1017-1033
Abstract
Ageing leads to a progressive loss of muscle function (MF) and quality (MQ: muscle strength (MS)/lean muscle mass (LM)). Power training and protein (PROT) supplementation have been proposed as efficient interventions to improve MF and MQ. Discrepancies between results appear to be mainly related to the type and/or dose of proteins used. The present study aimed at determining whether or not mixed power training (MPT) combined with fast-digested PROT (F-PROT) leads to greater improvements in MF and MQ in elderly men than MPT combined with slow-digested PROT (S-PROT) or MPT alone. Sixty elderly men (age 69 (sd 7) years; BMI 18-30 kg/m2) were randomised into three groups: (1) placebo + MPT (PLA; n 19); (2) F-PROT + MPT (n 21) and (3) S-PROT + MPT (n 20) completed the intervention. LM, handgrip and knee extensor MS and MQ, functional capacity, serum metabolic markers, skeletal muscle characteristics, dietary intake and total energy expenditure were measured. The interventions consisted in 12 weeks of MPT (3 times/week; 1 h/session) combined with a supplement (30 g:10 g per meal) of F-PROT (whey) or S-PROT (casein) or a placebo. No difference was observed among groups for age, BMI, number of steps and dietary intake pre- and post-intervention. All groups improved significantly their LM, lower limb MS/MQ, functional capacity, muscle characteristics and serum parameters following the MPT. Importantly, no difference between groups was observed following the MPT. Altogether, adding 30 g PROT/d to MPT, regardless of the type, does not provide additional benefits to MPT alone in older men ingesting an adequate (i.e. above RDA) amount of protein per d.
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Mitochondrial Content, but Not Function, Is Altered With a Multimodal Resistance Training Protocol and Adequate Protein Intake in Leucine-Supplemented Pre/Frail Women.
Jacob, KJ, Sonjak, V, Spendiff, S, Hepple, RT, Chevalier, S, Perez, A, Morais, JA
Frontiers in nutrition. 2020;:619216
Abstract
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.
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Ketone Monoester Supplementation Does Not Expedite the Recovery of Indices of Muscle Damage After Eccentric Exercise.
Martin-Arrowsmith, PW, Lov, J, Dai, J, Morais, JA, Churchward-Venne, TA
Frontiers in nutrition. 2020;:607299
Abstract
Purpose: The purpose of this study was to evaluate the effects of a ketone monoester supplement on indices of muscle damage during recovery after eccentric exercise. Methods: In a randomized, double-blind, independent group design, 20 moderately active healthy young adults consumed 360 mg per kg-1 bodyweight of a ketone monoester (KET) or energy-matched carbohydrate (CON) supplement twice daily following eccentric exercise (drop jumps). Maximal isometric voluntary contraction (MIVC) torque, counter-movement jump (CMJ) height, and muscle soreness were measured before (PRE), and immediately (POST), 24 h and 48 h post-exercise. Blood samples were collected for analysis of β-hydroxybutyrate (β-OHB), creatine kinase (CK), and select pro- and anti-inflammatory cytokines. Results: Peak blood β-OHB concentration after supplement intake was greater (P < 0.001) in KET (4.4 ± 0.8 mM) vs. CON (0.4 ± 0.3 mM). Exercise increased CK concentration at 24 h and 48 h vs. PRE (time: P < 0.001) with no difference between KET and CON. Exercise reduced MIVC (KET: -19.9 ± 14.6; CON: -22.6 ± 11.1%) and CMJ (KET: -11.0 ± 7.5; CON: -13.0 ± 8.7%) at POST relative PRE; however, there was no difference between KET and CON on the recovery of MIVC at 24 h (KET: -15.4 ± 20.4; CON: -18.7 ± 20.1%) or 48 h (KET: -7.2 ± 21.2; CON: -11.8 ± 20.2%), or CMJ at 24 h (KET: -9.2 ± 11.5; CON: -13.4 ± 10.8) or 48 h (KET: -12.5 ± 12.4; CON: -9.1 ± 11.7). Muscle soreness was increased during post-exercise recovery (time: P < 0.001) with no differences between KET and CON. Monocyte chemoattractant protein-1 was greater (group: P = 0.007) in CON (236 ± 11 pg/mL) vs. KET (187 ± 11 pg/mL). Conclusion: In conclusion, twice daily ingestion of a ketone monoester supplement that acutely elevates blood β-OHB concentration does not enhance the recovery of muscle performance or reduce muscle soreness following eccentric exercise in moderately active, healthy young adults.
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The conundrum of human immune system "senescence".
Pawelec, G, Bronikowski, A, Cunnane, SC, Ferrucci, L, Franceschi, C, Fülöp, T, Gaudreau, P, Gladyshev, VN, Gonos, ES, Gorbunova, V, et al
Mechanisms of ageing and development. 2020;:111357
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Abstract
There is a great deal of debate on the question of whether or not we know what ageing is (Ref. Cohen et al., 2020). Here, we consider what we believe to be the especially confused and confusing case of the ageing of the human immune system, commonly referred to as "immunosenescence". But what exactly is meant by this term? It has been used loosely in the literature, resulting in a certain degree of confusion as to its definition and implications. Here, we argue that only those differences in immune parameters between younger and older adults that are associated in some definitive manner with detrimental health outcomes and/or impaired survival prospects should be classed as indicators of immunosenescence in the strictest sense of the word, and that in humans we know remarkably little about their identity. Such biomarkers of immunosenescence may nonetheless indicate beneficial effects in other contexts, consistent with the notion of antagonistic pleiotropy. Identifying what could be true immunosenescence in this respect requires examining: (1) what appears to correlate with age, though generality across human populations is not yet confirmed; (2) what clearly is part of a suite of canonical changes in the immune system that happen with age; (3) which subset of those changes accelerates rather than slows aging; and (4) all changes, potentially population-specific, that accelerate agig. This remains an immense challenge. These questions acquire an added urgency in the current SARS-CoV-2 pandemic, given the clearly greater susceptibility of older adults to COVID-19.