Addressing cancer anorexia-cachexia in older patients: Potential therapeutic strategies and molecular pathways.

Cancer cachexia (CC) syndrome, a feature of cancer-associated muscle wasting, is particularly pronounced in older patients, and is characterised by decreased energy intake and upregulated skeletal muscle catabolic pathways. To address CC, appetite stimulants, anabolic drugs, cytokine mediators, essential amino acid supplementation, nutritional counselling, cognitive behavioural therapy, and enteral nutrition have been utilised. However, pharmacological treatments that have also shown promising results, such as megestrol acetate, anamorelin, thalidomide, and delta-9-tetrahydrocannabinol, have been associated with gastrointestinal and cardiovascular complications. Emerging evidence on the efficacy of probiotics in modulating gut microbiota also presents a promising adjunct to traditional therapies, potentially enhancing nutritional absorption and systemic inflammation control. Additionally, low-dose olanzapine has demonstrated improved appetite and weight management in older patients undergoing chemotherapy, offering a potential refinement to current therapeutic approaches. This review aims to elucidate the molecular mechanisms underpinning CC, with a particular focus on the role of anorexia in exacerbating muscle wasting, and to propose pharmacological and non-pharmacological strategies to mitigate this syndrome, particularly emphasising the needs of an older demographic. Future research targeting CC should focus on refining appetite-stimulating drugs with fewer side-effects, specifically catering to the needs of older patients, and investigating nutritional factors that can either enhance appetite or minimise suppression of appetite in individuals with CC, especially within this vulnerable group.

A Narrative Review of Non-Pharmacological Strategies for Managing Sarcopenia in Older Adults with Cardiovascular and Metabolic Diseases.

This narrative review examines the mechanisms underlying the development of cardiovascular disease (CVD) and metabolic diseases (MDs), along with their association with sarcopenia. Furthermore, non-pharmacological interventions to address sarcopenia in patients with these conditions are suggested. The significance of combined training in managing metabolic disease and secondary sarcopenia in type II diabetes mellitus is emphasized. Additionally, the potential benefits of resistance and aerobic training are explored. This review emphasises the role of nutrition in addressing sarcopenia in patients with CVD or MDs, focusing on strategies such as optimising protein intake, promoting plant-based protein sources, incorporating antioxidant-rich foods and omega-3 fatty acids and ensuring sufficient vitamin D levels. Moreover, the potential benefits of targeting gut microbiota through probiotics and prebiotic fibres in sarcopenic individuals are considered. Multidisciplinary approaches that integrate behavioural science are explored to enhance the uptake and sustainability of behaviour-based sarcopenia interventions. Future research should prioritise high-quality randomized controlled trials to refine exercise and nutritional interventions and investigate the incorporation of behavioural science into routine practices. Ultimately, a comprehensive and multifaceted approach is essential to improve health outcomes, well-being and quality of life in older adults with sarcopenia and coexisting cardiovascular and metabolic diseases.

Exploring the impact of exercise and essential amino acid plus cholecalciferol supplementation on physical fitness and body composition in multiple sclerosis: A case study.

Key Clinical Message: In MS patients, especially those frail or malnourished, combining home-based exercise twice weekly with essential amino acids and vitamin D may improve body composition, strength, and physical performance, enabling long-term functional improvements. Abstract: Multiple sclerosis (MS) is associated with reduced bone and muscle strength and function. We aimed to investigate the effectiveness of a 24-week intervention in a 57-year-old frail female with MS. The participant completed a 2×/week exercise intervention and ingested 2×/day a supplement containing 7.5 g essential amino acids and 500 IU cholecalciferol. Body composition, 6-m gait speed (GS), handgrip strength (HGS), 30-sec arm-curl test (30ACT), 6-min walking test (6MWT), 30-sec chair-stand test (30CST), and plasma concentrations of 25-hydroxyvitamin D3 [25(OH)D3], insulin-like growth factor 1 (IGF-1), and amino acids were assessed at baseline, and at Weeks 12 and 24. Plasma 25(OH)D3 increased from 23.2 to 41.3 ng/mL and IGF-1 from 131.6 to 140.7 ng/mL from baseline to post-intervention. BMI, total lean tissue mass (LTM), fat mass, bone mineral content, and the sum of 17 amino acids increased by 3.8, 1.0, 3.5, 0.2, and 19%, respectively, at Week 24. There were clinically significant increases in regional LTM (6.9% arms and 6.3% legs) and large increases in GS (67.3%), dominant HGS (31.5%), non-dominant HGS (11.8%), dominant 30ACT (100%), non-dominant 30ACT (116.7%), 6MWT (125.6%), and 30CST (44.4%). The current intervention was effective in improving components of physical fitness and body composition in a female with MS.

Handgrip strength is associated with learning and verbal fluency in older men without dementia: insights from the NHANES.

Low handgrip strength, a hallmark measure of whole-body strength, has been linked with greater odds of cognitive decline and dementia; however, conflicting findings, which could be due to population characteristics and choice of tools, such for the assessment of handgrip strength and cognitive function domains, also exist. Therefore, we examined the relationship of handgrip strength with a comprehensive list of tests to assess domains of cognitive function using a representative sample of US older men and women without neurodegenerative disorders such as dementia. We analyzed cross-sectional data from the US National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014, with a study cohort of 777 older adults (380 men and 397 women) above 60 years of age. Handgrip strength was assessed using a handgrip dynamometer, while cognitive function was assessed through the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List Learning Test (WLLT), Word List Recall Test (WLRT), Intrusion Word Count Test (WLLT-IC and WLRT-IC), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). Sex-stratified multiple linear regression analyses were performed upon covariate adjustment for age, ethnicity, socio-economic status, education, medical history, body mass index, physical activity, energy, protein, and alcohol intake. Maximal handgrip strength was positively associated with cognitive function scores, including CERAD WLLT (P = 0.009, R2 = 0.146) and AFT (P = 0.022, R2 = 0.024) in older men, but not in women (CERAD WLLT: P = 0.253, AFT: P = 0.370). No significant associations with CERAD WLLRT (men: P = 0.057, women: P = 0.976), WLLT-IC (men: P = 0.671, women: P = 0.869), WLLRT-IC (men: P = 0.111, women: P = 0.861), and DSST (men: P = 0.108, women: P = 0.091) were observed. Dose-response curves exhibited a prominent linear relationship between all significant associations after covariate adjustment, with no indication of a plateau in these relationships. In conclusion, higher handgrip strength was independently associated with better learning ability for novel verbal information and verbal fluency in US men over the age of 60 and without dementia. Longitudinal studies are required to confirm whether muscle strength independently predicts cognitive function changes in older adults in a sex-specific manner, and whether this connection is affirmed to the possibility of reverse causation due to declines in physical activity levels in the preclinical phase of dementia.

Impact of probiotics on muscle mass, muscle strength and lean mass: a systematic review and meta-analysis of randomized controlled trials.

Probiotics have shown potential to counteract sarcopenia, although the extent to which they can influence domains of sarcopenia such as muscle mass and strength in humans is unclear. The aim of this systematic review and meta-analysis was to explore the impact of probiotic supplementation on muscle mass, total lean mass and muscle strength in human adults. A literature search of randomized controlled trials (RCTs) was conducted through PubMed, Scopus, Web of Science and Cochrane Library from inception until June 2022. Eligible RCTs compared the effect of probiotic supplementation versus placebo on muscle and total lean mass and global muscle strength (composite score of all muscle strength outcomes) in adults (>18 years). To evaluate the differences between groups, a meta-analysis was conducted using the random effects inverse-variance model by utilizing standardized mean differences. Twenty-four studies were included in the systematic review and meta-analysis exploring the effects of probiotics on muscle mass, total lean mass and global muscle strength. Our main analysis (k = 10) revealed that muscle mass was improved following probiotics compared with placebo (SMD: 0.42, 95% CI: 0.10-0.74, I2  = 57%, P = 0.009), although no changes were revealed in relation to total lean mass (k = 12; SMD: -0.03, 95% CI: -0.19 - 0.13, I2  = 0%, P = 0.69). Interestingly, a significant increase in global muscle strength was also observed among six RCTs (SMD: 0.69, 95% CI: 0.33-1.06, I2  = 64%, P = 0.0002). Probiotic supplementation enhances both muscle mass and global muscle strength; however, no beneficial effects were observed in total lean mass. Investigating the physiological mechanisms underpinning different ageing groups and elucidating appropriate probiotic strains for optimal gains in muscle mass and strength are warranted.

Associations of Bioavailable Serum Testosterone With Cognitive Function in Older Men: Results From the National Health and Nutrition Examination Survey.

BACKGROUND: Age-associated cognitive decline may be influenced by testosterone status. However, studies evaluating the impact of bioavailable testosterone, the active, free testosterone, on cognitive function are scarce. Our study determined the relationship between calculated bioavailable testosterone and cognitive performance in older men. METHODS: We used data from the U.S. National Health and Nutrition Examination Survey (NHANES) between 2013 and 2014. This study consisted of 208 men aged ≥60 years. Bioavailable serum testosterone was calculated based on the total serum testosterone, sex hormone-binding globulin, and albumin levels, whereas cognitive performance was assessed through the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List Learning Test (WLLT), Word List Recall Test (WLRT), and Intrusion Word Count Test (WLLT-IC and WLRT-IC), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). Multiple linear regression analyses were performed upon adjustment for age, ethnicity, socioeconomic status, education level, medical history, body mass index, energy, alcohol intake, physical activity levels, and sleep duration. RESULTS: A significant positive association between bioavailable testosterone and DSST (ß: 0.049, p = .002) score was detected, with no signs of a plateau effect. No significant associations with CERAD WLLT (p = .132), WLRT (p = .643), WLLT-IC (p = .979), and WLRT-IC (p = .387), and AFT (p = .057) were observed. CONCLUSION: Calculated bioavailable testosterone presented a significant positive association with processing speed, sustained attention, and working memory in older men above 60 years of age. Further research is warranted to elucidate the impact of the inevitable age-related decline in testosterone on cognitive function in older men.

Aberrant mitochondrial homeostasis at the crossroad of musculoskeletal ageing and non-small cell lung cancer.

Cancer cachexia is accompanied by muscle atrophy, sharing multiple common catabolic pathways with sarcopenia, including mitochondrial dysfunction. This study investigated gene expression from skeletal muscle tissues of older healthy adults, who are at risk of age-related sarcopenia, to identify potential gene biomarkers whose dysregulated expression and protein interference were involved in non-small cell lung cancer (NSCLC). Screening of the literature resulted in 14 microarray datasets (GSE25941, GSE28392, GSE28422, GSE47881, GSE47969, GSE59880 in musculoskeletal ageing; GSE118370, GSE33532, GSE19804, GSE18842, GSE27262, GSE19188, GSE31210, GSE40791 in NSCLC). Differentially expressed genes (DEGs) were used to construct protein-protein interaction networks and retrieve clustering gene modules. Overlapping module DEGs were ranked based on 11 topological algorithms and were correlated with prognosis, tissue expression, and tumour purity in NSCLC. The analysis revealed that the dysregulated expression of the mammalian mitochondrial ribosomal proteins, Mitochondrial Ribosomal Protein S26 (MRPS26), Mitochondrial Ribosomal Protein S17 (MRPS17), Mitochondrial Ribosomal Protein L18 (MRPL18) and Mitochondrial Ribosomal Protein L51 (MRPL51) were linked to reduced survival and tumour purity in NSCLC while tissue expression of the same genes followed an opposite direction in healthy older adults. These results support a potential link between the mitochondrial ribosomal microenvironment in ageing muscle and NSCLC. Further studies comparing changes in sarcopenia and NSCLC associated cachexia are warranted.

Dietary Fiber Intake is Associated with Cognitive Function in Older Adults: Data from the National Health and Nutrition Examination Survey.

BACKGROUND: Aging is a global health challenge that is associated with a decline in cognitive function. In the United States, most older adults (≥50 years) do not meet the recommended daily fiber intake, although preliminary evidence suggests that dietary fiber consumption could elicit clinical benefits on cognitive function. We investigated the associations between dietary fiber intake and cognitive function in older adults. METHODS: We analyzed data from the US National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014, with a study cohort of 1070 older adults (≥60 years). Cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning Test (WLT), Word Recall Test (WRT) and their Intrusion Word Count Tests (WLT-IC and WRT-IC), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). Multiple linear regression and cubic spline analyses were employed to examine the association between dietary fiber intake and cognitive performance on a test-by-test basis, after covariates adjustment (ie, age, sex, race, socioeconomic status, educational level, medical history, body mass index, alcohol, and energy intake). RESULTS: Participants had a mean age of 69.2 years and were primarily non-Hispanic white of middle-high socioeconomic status with a college degree at minimum. The mean dietary fiber intake was 17.3 g/d. The analysis showed that dietary fiber intake was positively associated with DSST (P = .031). No associations with CERAD WLT (P = .41), WRT (P = .68), WLT-IC (P = .07), and WRT-IC (P = .28), and AFT (P = .40) scores were observed. A plateau in DSST score was revealed at a dietary fiber intake of 34 g/d. CONCLUSIONS: Higher dietary fiber intake is associated with improved specific components of cognitive function in older adults aged 60 years and older. Public health interventions that target a recommended dietary fiber intake may provide a promising strategy to combat cognitive decline in high-risk groups of older adults.

The impact of different forms of exercise on endothelial progenitor cells in healthy populations.

Circulating endothelial progenitor cells (EPCs) contribute to vascular healing and neovascularisation, while exercise is an effective means to mobilise EPCs into the circulation. OBJECTIVES: to systematically examine the acute and chronic effects of different forms of exercise on circulating EPCs in healthy populations. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. RESULTS: thirty-one articles met the inclusion criteria including 747 participants aged 19 to 76 years. All included trials used flow cytometry for identification of circulating EPCs. Eight and five different EPC phenotypes were identified in the acute and chronic trials, respectively. In the acute trials, moderate intensity continuous (MICON), maximal, prolonged endurance, resistance and high intensity interval training (HIIT) exercise protocols were utilised. Prolonged endurance and resistance exercise had the most profound effect on circulating EPCs followed by maximal exercise. In the chronic trials, MICON exercise, HIIT, HIIT compared to MICON and MICON compared to exergame (exercise modality based on an interactive video game) were identified. MICON exercise had a positive effect on circulating EPCs in older sedentary individuals which was accompanied by improvements in endothelial function and arterial stiffness. Long-stage HIIT (4 min bouts) appears to be an effective means and superior than MICON exercise in mobilising circulating EPCs. In conclusion, both in acute and chronic trials the degree of exercise-induced EPC mobilisation depends upon the exercise regime applied. In future, more research is warranted to examine the dose-response relationship of different exercise forms on circulating EPCs using standardised methodology and EPC phenotype.

The impact of different forms of exercise on circulating endothelial progenitor cells in cardiovascular and metabolic disease.

Circulating endothelial progenitor cells (EPCs) contribute to vascular repair and their monitoring could have prognostic clinical value. Exercise is often prescribed for the management of cardiometabolic diseases, however, it is not fully understood how it regulates EPCs. OBJECTIVES: to systematically examine the acute and chronic effects of different exercise modalities on circulating EPCs in patients with cardiovascular and metabolic disease. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. RESULTS: six electronic databases and reference lists of eligible studies were searched to April 2021. Thirty-six trials met the inclusion criteria including 1731 participants. Acute trials: in chronic heart failure (CHF), EPC mobilisation was acutely increased after high intensity interval or moderate intensity continuous exercise training, while findings were inconclusive after a cardiopulmonary cycling exercise test. Maximal exercise tests acutely increased EPCs in ischaemic or revascularized coronary artery disease (CAD) patients. In peripheral arterial disease (PAD), EPC levels increased up to 24 h post-exercise. In patients with compromised metabolic health, EPC mobilisation was blunted after a single exercise session. Chronic trials: in CHF and acute coronary syndrome, moderate intensity continuous protocols, with or without resistance exercise or calisthenics, increased EPCs irrespective of EPC identification phenotype. Findings were equivocal in CAD regardless of exercise mode, while in severe PAD disease EPCs increased. High intensity interval training increased EPCs in hypertensive metabolic syndrome and heart failure reduced ejection fraction. CONCLUSION: the clinical condition and exercise modality influence the degree of EPC mobilisation and magnitude of EPC increases in the long term.

Nutritional status and intake in patients with non-cystic fibrosis bronchiectasis (NCFB) - a cross sectional study.

BACKGROUND & AIMS: Bronchiectasis is a heterogeneous, chronic respiratory condition, in which the role of nutrition remains unclear and nutritional guidance is lacking. Few studies have explored the role of nutrition in disease management, and little is known about nutritional requirements during periods of stability or metabolic stress. The aim of this study was to characterise nutritional status and intakes in a cohort of patients and identify potential associations with body composition and functional capacity. METHODS: A prospective observational cohort study was undertaken in an adult population (>17 years). Bronchiectasis was confirmed by high-resolution computerised tomography (HRCT). Anthropometric (weight, height, Body Mass Index (BMI), triceps skinfold thickness (TSF), mid upper-arm circumference (MUAC) and mid arm muscle circumference (MAMC)] lung function and nutritional intakes were measured. Results were analysed as a whole and by disease aetiology [primary ciliary dyskinesia (PCD), Idiopathic cause (IC), bronchiectasis in association with asthma and other] and associations tested. RESULTS: In total, 128 participants (65.5% female) completed the study. Median handgrip strength (HGS) in the total sample was only 66.5% (IQR 60.5-89.8) of reference population norms and was low for those with PCD [58.0% (IQR 43.5-70.0))]. Univariate regression indicated that BMI was a statistically significant predictor of lung function in the whole population with HGS and weight identified as statistically significant predictors of lung function in PCD. The total population and each sub-group failed to meet estimated average requirements for energy but exceeded the Reference nutrient intake (RNI) for protein. Vitamin D was consistently <35% of the RNI. CONCLUSION: BMI lay within normal to overweight ranges within the whole population and sub-groups, but masked important functional, body composition and nutritional deficits. This was particularly so within a younger sub-group with PCD, who had impaired muscle function, when compared to other causal and associative diseases.

The effects of an acute resistance exercise bout on appetite and energy intake in healthy older adults.

Ageing is associated with reductions in appetite and food intake leading to unintentional weight loss. Such weight loss, particularly through muscle mass reduction, is associated with muscle weakness and functional decline, which represent predictors of poor health outcomes and contribute to frailty in older adults. Exercise-induced anorexia is an established phenomenon in young adults; however appetite and energy intake (EI) responses to resistance exercise are unknown in older adults. Twenty healthy older adults (68 ± 5 years, BMI 26.2 ± 4.5 kg m-2) undertook two 5-h experimental trials. Participants rested for 30 min before being provided with a standardised breakfast (196 kcal, 75.2% carbohydrate, 8.9% protein and 15.9% fat). Participants then rested for 1-h before completing: 1-h resistance exercise bout followed by 2-h of rest (RE) or, a control condition (CON) where participants rested for 3 h, in a randomised crossover design. Appetite perceptions were measured throughout both trials and on cessation, an ad libitum meal was provided to assess EI. A repeated-mesures ANOVA revealed no significant condition x time interaction for subjective appetite (p = 0.153). However, area under the curve for appetite was significantly lower in the RE compared with CON (49 ± 8 mm h-1 vs. 52 ± 9 mm h-1, p = 0.007, d = 0.27). There was no difference in EI (RE = 681 ± 246 kcal; CON = 673 ± 235 kcal; p = 0.865), suggesting that resistance exercise does not affect EI 2 h post-exercise in older adults despite a significant but modest reduction in appetite over a 5-h period. In conclusion, resistance exercise may be an appropriate means for optimising muscle mass adaptations without attenuating acute EI of older adults.

An Increase in Fat-Free Mass is Associated with Higher Appetite and Energy Intake in Older Adults: A Randomised Control Trial.

Cross-sectional studies in younger adults have demonstrated a positive association between energy intake (EI) and fat-free mass (FFM), with this relationship seemingly mediated by resting metabolic rate (RMR). Establishing a causal effect longitudinally would be prudent in older adults suffering from loss of appetite. We investigated the effects of FFM on RMR, appetite and EI in 39 healthy older adults (age: 66 ± 4 years, BMI: 25.1 ± 3.5 kg∙m2) assigned to either 12-week resistance training + protein supplementation group (RT + PRO) or control group (CON). Body composition, subjective appetite, leptin, insulin, RMR and laboratory-measured ad libitum EI were measured at baseline, weeks 6 and 12 of the intervention, while daily EI at baseline and week 12. FFM (+1.2 kg; p = 0.002), postprandial subjective appetite (+8 mm; p = 0.027), ad libitum EI (+119 kcal; p = 0.012) and daily EI (+133 kcal; p = 0.010) increased from baseline to week 12 in the RT + PRO. RMR, fasted subjective appetite, leptin and insulin concentrations remained unchanged (all p > 0.05). The increases ad libitum EI correlated with increases in FFM (r = 0.527, p = 0.001), with 54% of the change in EI attributed to FFM changes. In conclusion, FFM increases were associated with an increased ad libitum EI and postprandial appetite in older adults.

The efficacy of essential amino acid supplementation for augmenting dietary protein intake in older adults: implications for skeletal muscle mass, strength and function.

The primary aim of this review is to evaluate the efficacy of essential amino acid (EAA) supplementation as a strategy to increase dietary protein intake and improve muscle mass, strength and function in older adults. A sufficient daily protein intake is widely recognised to be fundamental for the successful management of sarcopenia in older undernourished adults. In practice, optimising protein intakes in older adults is complex, requiring consideration of the dose and amino acid composition (i.e. a complete EAA profile and abundant leucine content) of ingested protein on a per meal basis, alongside the age-related decline in appetite and the satiating properties of protein. Recent studies in older adults demonstrate that EAA-based supplements are non-satiating and can be administered alongside food to enhance the anabolic properties of a meal containing a suboptimal dose of protein; an effect magnified when combined with resistance exercise training. These findings support the notion that EAA supplementation could serve as an effective strategy to improve musculoskeletal health in older adults suffering from non-communicable diseases such as sarcopenia. Compliance is critical for the long-term success of complex interventions. Hence, aspects of palatability and desire to eat are important considerations regarding EAA supplementation. In conclusion, EAA-based supplements enriched with l-leucine offer an alternative strategy to whole protein sources to assist older adults in meeting protein recommendations. In practice, EAA supplements could be administered alongside meals of suboptimal protein content, or alternatively between meals on occasions when older adults achieve their per meal protein intake recommendations.

UK cardiac rehabilitation fit for purpose? A community-based observational cohort study.

OBJECTIVES: This study aimed to characterise the exercise performed in UK cardiac rehabilitation (CR) and explore relationships between exercise dose and changes in physiological variables. DESIGN: Observational cohort study. SETTING: Outpatient community-based CR in Leeds, UK. Rehabilitation sessions were provided twice per week for 6 weeks. PARTICIPANTS: Sixty patients (45 male/15 female 33-86 years) were recruited following referral to local outpatient CR. OUTCOME MEASURES: The primary outcome was heart rate achieved during exercise sessions. Secondary outcomes were measured before and after CR and included incremental shuttle walk test (ISWT) distance and speed, blood pressure, brachial artery flow-mediated dilatation, carotid arterial stiffness and accelerometer-derived habitual physical activity behaviours. RESULTS: The mean % of heart rate reserve patients exercised at was low and variable at the start of CR (42%±16 %) and did not progress by the middle (48%±17 %) or end (48%±16 %) of the programme. ISWT performance increased following CR (440±150 m vs 633±217 m, p<0.001); however, blood pressure, body weight, endothelial function, arterial stiffness and habitual physical activity behaviours were unchanged following 6 weeks of CR (p>0.05). CONCLUSION: Patients in a UK CR cohort exercise at intensities that are variable but generally low. The exercise dose achieved using this CR format appears inadequate to impact markers of health. Attending CR had no effect on physical activity behaviours. Strategies to increase the dose of exercise patients achieve during CR and influence habitual physical activity behaviours may enhance the effectiveness of UK CR.

Novel Essential Amino Acid Supplements Following Resistance Exercise Induce Aminoacidemia and Enhance Anabolic Signaling Irrespective of Age: A Proof-of-Concept Trial.

We investigated the effects of ingesting a leucine-enriched essential amino acid (EAA) gel alone or combined with resistance exercise (RE) versus RE alone (control) on plasma aminoacidemia and intramyocellular anabolic signaling in healthy younger (28 ± 4 years) and older (71 ± 3 years) adults. Blood samples were obtained throughout the three trials, while muscle biopsies were collected in the postabsorptive state and 2 h following RE, following the consumption of two 50 mL EAA gels (40% leucine, 15 g total EAA), and following RE with EAA (combination (COM)). Protein content and the phosphorylation status of key anabolic signaling proteins were determined via immunoblotting. Irrespective of age, during EAA and COM peak leucinemia (younger: 454 ± 32 µM and 537 ± 111 µM; older: 417 ± 99 µM and 553 ± 136 µM) occurred ~60-120 min post-ingestion (younger: 66 ± 6 min and 120 ± 60 min; older: 90 ± 13 min and 78 ± 12 min). In the pooled sample, the area under the curve for plasma leucine and the sum of branched-chain amino acids was significantly greater in EAA and COM compared with RE. For intramyocellular signaling, significant main effects were found for condition (mTOR (Ser2481), rpS6 (Ser235/236)) and age (S6K1 (Thr421/Ser424), 4E-BP1 (Thr37/46)) in age group analyses. The phosphorylation of rpS6 was of similar magnitude (~8-fold) in pooled and age group data 2 h following COM. Our findings suggest that a gel-based, leucine-enriched EAA supplement is associated with aminoacidemia and a muscle anabolic signaling response, thus representing an effective means of stimulating muscle protein anabolism in younger and older adults following EAA and COM.

Differences in circulating appetite-related hormone concentrations between younger and older adults: a systematic review and meta-analysis.

Ageing is associated with reduced appetite and energy intakes. However, the mechanisms underlying this phenomenon are not fully understood. This systematic review and meta-analysis quantified differences in circulating concentrations of appetite-related hormones between healthy older and younger adults. Six databases were searched through 12th June 2018 for studies that compared appetite-related hormone concentrations between older and younger adults. Data were pooled using random-effects meta-analysis and are presented as standardised mean difference (Hedges' g) with 95% confidence intervals (95% CI). Thirty-five studies were included involving 710 older adults (mean ± SD; age: 73 ± 5 years) and 713 younger adults (age: 28 ± 7 years). Compared with younger adults, older adults exhibited higher fasted and postprandial concentrations of the anorectic hormones cholecystokinin (Fasted: SMD 0.41 (95% CI 0.24, 0.57); p < 0.001. Postprandial: SMD 0.41 (0.20, 0.62); p < 0.001), leptin [Fasted: SMD 1.23 (0.15, 2.30); p = 0.025. Postprandial: SMD 0.62 (0.23, 1.01); p = 0.002] and insulin [Fasted: SMD 0.24 (- 0.02, 0.50); p = 0.073. Postprandial: SMD 0.16 (0.01, 0.32); p = 0.043]. Higher postprandial concentrations of peptide-YY were also observed in older adults compared with younger adults [SMD 0.31 (- 0.03, 0.65); p = 0.075]. Compared with younger adults, older adults had lower energy intakes [SMD - 0.98 (- 1.74, - 0.22); p = 0.011], and lower hunger perceptions in the fasted [SMD - 1.00 (- 1.54, - 0.46); p < 0.001] and postprandial states [SMD - 0.31, (- 0.64, 0.02); p = 0.064]. Higher circulating concentrations of insulin, leptin, cholecystokinin and peptide-YY accord with reduced appetite and energy intakes in healthy older adults. Interventions to reduce circulating levels of these hormones may be beneficial for combatting the anorexia of ageing.

Αcute effects of essential amino acid gel-based and whey protein supplements on appetite and energy intake in older women.

Deficiencies in protein and energy intakes are partly responsible for age-related sarcopenia. We investigated the effects of supplements matched in essential amino acid (EAA) content (7.5 g) on energy intake and appetite. Ten women aged 69.2 ± 2.7 years completed 3 trials in a randomised, crossover design. Composite appetite scores, peptide-YY (PYY), and insulin responses to a 200-mL whey protein (WP) isolate (275 kJ), a 50-mL EAA gel (GEL, 478 kJ), or nothing as the control (CON) condition were investigated over 1 h, followed by an ad libitum breakfast. Energy intake at breakfast (CON, 1957 ± 713; WP, 1413 ± 623; GEL, 1963 ± 611 kJ) was higher in CON and GEL than in WP (both P = 0.006). After accounting for supplement energy content, energy intake in GEL was higher than in CON (P = 0.0006) and WP (P = 0.0008). Time-averaged area under the curve for composite appetite scores (CON, 74 ± 20; WP, 50 ± 22; GEL, 60 ± 16 mm) was higher in CON than WP (P = 0.015). Time-averaged area under the curve for PYY (CON, 87 ± 13; WP, 119 ± 27; GEL, 97 ± 22 pg·mL-1) was higher in WP than CON (P = 0.009) and GEL (P = 0.012). In conclusion, supplementation with WP facilitated an increase in protein intake, whereas supplementation with GEL increases in both energy and protein intakes, when consumed before an ad libitum breakfast. Such findings highlight potential gel-based EAA supplementation intake for addressing age-related sarcopenia.

Muscle quality as a complementary prognostic tool in conjunction with sarcopenia assessment in younger and older individuals.

PURPOSE: This pilot study investigated differences in lean tissue mass, muscle strength, muscle quality (strength per unit of muscle mass; MQ), and functional performance in healthy younger and older individuals. The most robust predictors of appendicular lean mass (ALM) were then determined in each group. METHODS: Fifty younger (18-45 years) and 50 older (60-80 years) participants completed tests of upper and lower body strength alongside body composition by dual-energy X-ray absorptiometry from which upper- and lower-body MQ were estimated. Available cut-points for older people were used to determine low upper-body MQ in both groups. Low lower-body MQ was determined as at least two standard deviations below the mean of the younger group. Functional performance was assessed by gait speed. Sarcopenia was identified using two established definitions. RESULTS: Upper and lower body strength, ALM, lower-body MQ and gait speed were significantly higher in the younger group (all p < 0.002). Sarcopenia was identified in 2-4% of the older group. Low upper-body MQ was evident in 32% and 42% of the younger and older group, respectively. Low lower-body MQ was observed in 4% of younger participants, and 50% of older participants. In both groups, the most robust predictors of ALM were upper and lower body strength (young R2 = 0.74, 0.82; older R2 = 0.68, 0.72). CONCLUSIONS: Low MQ despite low prevalence rates of sarcopenia in both groups suggests a need for age-specific MQ cut-points. Muscle quality assessments might be useful complementary prognostic tools alongside existing sarcopenia definitions.