Biomarkers of aging for the identification and evaluation of longevity interventions.

With the rapid expansion of aging biology research, the identification and evaluation of longevity interventions in humans have become key goals of this field. Biomarkers of aging are critically important tools in achieving these objectives over realistic time frames. However, the current lack of standards and consensus on the properties of a reliable aging biomarker hinders their further development and validation for clinical applications. Here, we advance a framework for the terminology and characterization of biomarkers of aging, including classification and potential clinical use cases. We discuss validation steps and highlight ongoing challenges as potential areas in need of future research. This framework sets the stage for the development of valid biomarkers of aging and their ultimate utilization in clinical trials and practice.

Respiratory Muscle Strength Is Related to Handgrip Performance in Community-Dwelling Persons Aged 80+ from the BUTTERFLY Study.

INTRODUCTION: This study aimed to evaluate the association of respiratory muscle strength with sarcopenia and its indicators in the oldest old. METHODS: Maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and sarcopenia-related factors (handgrip strength and appendicular lean mass) were evaluated in a cohort of n = 286 (45.5% female) non-frail, community-dwelling persons aged 83.6 ± 3.0 years (age range 80-97 years). RESULTS: The sample presented a sarcopenia prevalence of 32.2%. Sarcopenic subjects showed comparable MIP and MEP as non-sarcopenic ones (female: MIP 43.9 ± 18.9 vs. 50.3 ± 19.5, p = 0.053; MEP 63.0 ± 23.0 vs. 69.2 ± 19.1, p = 0.067; male: MIP, 65.1 ± 24.4 vs. 64.4 ± 23.9, p = 0.433; MEP 87.7 ± 33.3 vs. 93.8 ± 30.9, p = 0.124). Statistically significant but very low associations were found between grip strength and MIP (r = 0.193 for male, p < 0.05 and r = 0.257 for female participants, p < 0.01) and MEP (r = 0.200 for male, p < 0.01 and r = 0.191 for female participants, p < 0.05). Lean mass was significantly correlated to MIP and MEP in female (r = 0.253, p < 0.01 and r = 0.343, p < 0.01, respectively), whereas this association was not found in male participants. Grip strength was the only statistically significant predictor of MEP (r2 = 0.212, p < 0.001), while MIP was independently predicted by age, male sex, and grip strength (r2 = 0.177, p < 0.001). CONCLUSIONS: Peripheral muscle strength is a statistically significant, albeit weak predictor for respiratory muscle strength in well-functioning, community-dwelling persons aged 80+. When confronted to a low grip strength, one should be aware of concomitant respiratory muscle weakness, as this is a known risk factor for atelectasis and pneumonia. Given the relatively low association with handgrip strength, respiratory muscle strength testing might be indicated.

A State-of-the-Art of Exoskeletons in Line with the WHO's Vision on Healthy Aging: From Rehabilitation of Intrinsic Capacities to Augmentation of Functional Abilities.

The global aging population faces significant health challenges, including an increasing vulnerability to disability due to natural aging processes. Wearable lower limb exoskeletons (LLEs) have emerged as a promising solution to enhance physical function in older individuals. This systematic review synthesizes the use of LLEs in alignment with the WHO's healthy aging vision, examining their impact on intrinsic capacities and functional abilities. We conducted a comprehensive literature search in six databases, yielding 36 relevant articles covering older adults (65+) with various health conditions, including sarcopenia, stroke, Parkinson's Disease, osteoarthritis, and more. The interventions, spanning one to forty sessions, utilized a range of LLE technologies such as Ekso®, HAL®, Stride Management Assist®, Honda Walking Assist®, Lokomat®, Walkbot®, Healbot®, Keeogo Rehab®, EX1®, overground wearable exoskeletons, Eksoband®, powered ankle-foot orthoses, HAL® lumbar type, Human Body Posturizer®, Gait Enhancing and Motivation System®, soft robotic suits, and active pelvis orthoses. The findings revealed substantial positive outcomes across diverse health conditions. LLE training led to improvements in key performance indicators, such as the 10 Meter Walk Test, Five Times Sit-to-Stand test, Timed Up and Go test, and more. Additionally, enhancements were observed in gait quality, joint mobility, muscle strength, and balance. These improvements were accompanied by reductions in sedentary behavior, pain perception, muscle exertion, and metabolic cost while walking. While longer intervention durations can aid in the rehabilitation of intrinsic capacities, even the instantaneous augmentation of functional abilities can be observed in a single session. In summary, this review demonstrates consistent and significant enhancements in critical parameters across a broad spectrum of health conditions following LLE interventions in older adults. These findings underscore the potential of LLE in promoting healthy aging and enhancing the well-being of older adults.

Additional effects of exercise to hypocaloric diet on body weight, body composition, glycaemic control and cardio-respiratory fitness in adults with overweight or obesity and type 2 diabetes: A systematic review and meta-analysis.

AIMS: This systematic review and meta-analysis evaluates the additional effect of exercise to hypocaloric diet on body weight, body composition, glycaemic control and cardio-respiratory fitness in adults with overweight or obesity and type 2 diabetes. METHODS: Embase, Medline, Web of Science and Cochrane Central databases were evaluated, and 11 studies were included. Random-effects meta-analysis was performed on body weight and measures of body composition and glycaemic control, to compare the effect of hypocaloric diet plus exercise with hypocaloric diet alone. RESULTS: Exercise interventions consisted of walking or jogging, cycle ergometer training, football training or resistance training and duration varied from 2 to 52 weeks. Body weight and measures of body composition and glycaemic control decreased during both the combined intervention and hypocaloric diet alone. Mean difference in change of body weight (-0.77 kg [95% CI: -2.03; 0.50]), BMI (-0.34 kg/m2 [95% CI: -0.73; 0.05]), waist circumference (-1.42 cm [95% CI: -3.84; 1.00]), fat-free mass (-0.18 kg [95% CI: -0.52; 0.17]), fat mass (-1.61 kg [95% CI: -4.42; 1.19]), fasting glucose (+0.14 mmol/L [95% CI: -0.02; 0.30]), HbA1c (-1 mmol/mol [95% CI: -3; 1], -0.1% [95% CI: -0.2; 0.1]) and HOMA-IR (+0.01 [95% CI: -0.40; 0.42]) was not statistically different between the combined intervention and hypocaloric diet alone. Two studies reported VO2max and showed significant increases upon the addition of exercise to hypocaloric diet. CONCLUSIONS: Based on limited data, we did not find additional effects of exercise to hypocaloric diet in adults with overweight or obesity and type 2 diabetes on body weight, body composition or glycaemic control, while cardio-respiratory fitness improved.

Exercise-induced effects on inflammatory markers and brain-derived neurotrophic factor in patients with knee osteoarthritis. A systematic review with meta-analysis.

Background: In the pathogenesis of knee osteoarthritis (KOA), inflammatory mediators play an important role. However, the precise underlying mechanism by which regular exercise therapy (ET) exert effects on the immune system in KOA patients is unknown. Objectives: The aim of this systematic review was to investigate the basal and acute effects of ET on inflammatory biomarkers and brain derived neurotrophic factor (BDNF) in KOA patients. Methods: PubMed, Web Of Science and PEDro were systematically searched for appropriate studies. If possible, a meta-analysis was performed or an approximation of the effect size (ES) was calculated. Risk of bias was scored using the Cochrane ROB 2.0 or ROBINS-tools. Results: Twenty-one studies involving 1374 participants were included. Fifteen articles focused on basal exercise effects, four on acute effects, and two on both. Biomarker analysis (n=18) was performed in synovial fluid (n=4) or serum/plasma (n=17). A meta-analysis demonstrated that basal CRP was reduced in KOA patients 6-18 weeks weeks after ET (MD: -0.17;95%CI[-0.31;-0.03]), while IL-6 (MD: 0.21;95%CI[-0.44;0.85]), and TNF-α (MD: -0.57;95%CI[-1.47;0.32]), levels did not significantly change. Also, sTNFR1/2 did not change significantly after ET. For other biomarkers, insufficient data were available to perform a meta-analysis. Nevertheless, a low degree of evidence was found for a decrease in IL-6 (ES:-0.596 & -0.259 & -0.513), an increase in sTNFR1 (ES:2.325), a decrease in sTNFR2 (ES:-0.997) and an increase in BDNF (ES:1.412). Locally, intra-articular IL-10 (ES:9.163) increased, and IL1ß (ES:-6.199) and TNF-α decreased (ES:-2.322) after ET. An acute exercise session elicited a myokine response (ES IL-6:0.314), and an increase in BDNF (no ES-data). No inflammatory effect (ES CRP:0.052; ES TNF-α:-0.019 & 0.081) following an acute bout of training was found. However, a single bout of exercise elicited a decrease in intra-articular IL-10 (no ES-data). Conclusion: ET can induce circulatory and intra-articular anti-inflammatory effects in patients with KOA. The antiinflammatory properties have important implications for informing these patients and clinicians about the underlying effects of ET.

Measurement properties of instruments to measure the fatigue domain of vitality capacity in community-dwelling older people: an umbrella review of systematic reviews and meta-analysis.

BACKGROUND: Vitality capacity (VC) is a key domain of intrinsic capacity (IC) and is the underlying biophysiological aspect of IC. Energy and metabolism (E&M) is one of the domains of VC. Fatigue is one of the main characteristics of E&M. OBJECTIVE: The aims of this umbrella review are (i) to identify the available instruments suitable for measuring fatigue in community-dwelling older adults and (ii) to critically review the measurement properties of the identified instruments. DESIGN: Umbrella review. SETTING: Healthcare. SUBJECTS: Community-dwelling older adults. METHODS: PubMed and Web of Knowledge were systematically screened for systematic reviews and meta-analysis reporting on fatigue instruments resulting in 2,263 articles (last search 5 December 2022). The COSMIN checklist was used to appraise psychometric properties and the AMSTAR for assessing methodological quality. Data on fatigue instruments, construct, reference period, assessment method, validated population, reliability, validity, responsiveness and predictive validity on negative health outcomes were extracted. RESULTS: 10 systematic reviews and 1 meta-analysis were included in this study. 70 fatigue instruments were identified in the literature and 21 were originally designed for fatigue. The Fatigue Severity Scale (FSS), Pittsburgh Fatigability Scale (PFS) and Visual Analogue scale (VAS-F), Fatigue Impact Scale (FIS) and the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) presented good psychometric properties. CONCLUSIONS: The FSS, FIS, FACIT-F, PFS and the VAS-F presented good psychometric properties in various conditions. Therefore, these instruments could be used to quantify trajectories in the domain E&M in the context of VC in community-dwelling older adults.

Comparison between Two Different Handgrip Systems and Protocols on Force Reduction in Handgrip Assessment.

INTRODUCTION: Fatigue resistance (FR) can be assessed as the time during which grip strength (GS) drops to 50% of its maximum during a sustained maximal voluntary contraction. For the first time, we compared force-time characteristics during FR test between two different handgrip systems and investigated age- and clinical-related differences in order to verify if a briefer test protocol (i.e., until 75%) could be sufficiently informative. METHODS: A cohort of young healthy controls (Y, <30 y, 24 ± 3 y, 54% women), middle-aged (MA, 30-65 y, 47 ± 11 y, 54% women), and older (OLD, >65 y, 77 ± 7 y, 50% women) community-dwelling persons, and hospitalized geriatric patients (HOSP, 84 ± 5 y, 50% women) performed the FR test. For this purpose, an adapted vigorimeter (original rubber bulb of the Martin Vigorimeter connected to a Unik 5000 pressure gauge) here defined as "pneumatic handgrip system" (Pneu) and Dynamometer G200 system (original Jamar Dynamometer handle with an in-build strength gauge) here defined as "hydraulic handgrip system" (Hydr) were used. Force-time curves were analysed from 100% to 75% and from 75% to 50% of the initial maximal GS during the FR test. The area under the curve (GW) was calculated by integrating the actual GS at each time interval (i.e., 1/5,000 s) and corrected for body weight (GW/body weight). RESULTS: For both systems, we found fair associations between FR100-50 and FR100-75 (Pneu mean difference = 50.1 s [95% CI: 47.9-52.4], r2 = 0.48; Hydr mean difference = 28.4 s [95% CI: 27.0-29.7], r2 = 0.52, all p < 0.001) and also moderate associations between GW(100-50)/body weight and GW(100-75)/body weight (Pneu mean difference = 32.1 kPa*s/kg [95% CI: 30.6-33.6], r2 = 0.72; Hydr mean difference = 8.1 kg*s/kg [95% CI: 7.7-8.6], r2 = 0.68, all p < 0.001). Between MA and OLD, we found a significant age-related difference in the GW results in the first 25% strength decay for Pneu (10.2 ± 0.6 kPa*s/kg against 7.1 ± 1.2 kPa*s/kg, respectively). CONCLUSION: The brief test protocol is valid. Differences within the first 25% strength decay in GW between OLD and HOSP were identified when using Pneu but not when using Hydr. Therefore, a brief FR test protocol using a continuous registration of the strength decay seems to be sufficiently informative in a clinical setting to appraise muscle fatigability, however, only when using a Pneu system.

Transitions in robust and prefrail octogenarians after 1 year: the influence of activities of daily living, social participation, and psychological resilience on the frailty state.

BACKGROUND: Knowledge opportunities lie ahead as everyday activities, social participation, and psychological resilience might be important predictors for frailty state transitioning in the oldest old. Therefore, this article aims to examine whether changes in basic-, instrumental-, advanced- activities of daily living (b-, i-, a-ADLs), social participation, and psychological resilience predict both a transition from robustness to prefrailty or frailty and vice versa among community-dwelling octogenarians over a follow-up period of one year. METHODS: To evaluate worsened and improved frailty transitions after one year in 322 octogenarians (Mage = 83.04 ± 2.78), the variables sex, ADLs (b-ADL-DI, i-ADL-DI, a-ADL-DI as baseline and as difference after 6 months values), the CD-RISC (Connor-Davidson Resilience Scale, as baseline and as difference after 6 months), the social participation variables (total participation score, being a member, total number of memberships, level of social participation, being a board member, volunteering, and formal participation as baseline and as difference after 6 months values), were included in a logistic regression analysis. RESULTS: Limitations in a-ADLs at baseline (OR: 1.048, 95% confidence interval, 1.010-1.090) and an increment of limitations in a-ADLs after 6 months (OR: 1.044, 95% confidence interval, 1.007-1.085) were predictors to shift from robust to a worsened frailty state after one year follow-up. Additionally, being a woman (OR: 3.682, 95% confidence interval, 1.379-10.139) and social participation, specifically becoming a board member in 6 months (OR: 4.343, 95% confidence interval, 1.082-16.347), were protectors of robustness and thus related to an improved frailty transition after one year. CONCLUSIONS: Encouraging healthy lifestyle behaviors to help the maintenance of ADLs, possibly leading to more social participation, could be promising in the prevention of frailty.

Measuring health-related quality of life in sarcopenia: summary of the SarQoL psychometric properties.

Patient perspectives are now widely recognized as a key element in the evaluation of health interventions. Therefore, the provision of specific and validated Patient Reported Outcome Measures that emphasize the lived experience of patients suffering from specific diseases is very important. In the field of sarcopenia, the only validated specific health-related quality of life (HRQoL) instrument available is the Sarcopenia Quality of Life questionnaire (SarQoL). This self-administrated HRQoL questionnaire, developed in 2015, consists of 55 items arranged into 22 questions and has currently been translated into 35 languages. Nineteen validation studies performed on SarQoL have consensually confirmed the capacity of SarQoL to detect difference in HRQoL between older people with and without sarcopenia, its reliability and its validity. Two further observational studies have also indicated its responsiveness to change. A short form SarQoL, including only 14 items has further been developed and validated to reduce the potential burden of administration. Research on the psychometric properties of SarQoL questionnaire is still encouraged as the responsiveness to change of SarQoL has not yet been measured in the context of interventional studies, as limited prospective data currently exist and as there is still not cut-off score to define a low HRQoL. In addition, SarQoL has mainly been used in community-dwelling older individuals with sarcopenia and would benefit to be studied in other types of populations. This review aims to provide to researchers, clinicians, regulators, pharmaceutical industries and other stakeholders a clear summary of comprehensive evidence on the SarQoL questionnaire published up to January 2023Query.

Validity and reliability of Eforto®, a system to (self-)monitor grip strength and muscle fatigability in older persons.

INTRODUCTION: We developed Eforto®, an innovative system for (self-)monitoring of grip strength (GS) and muscle fatigability (Fatigue Resistance (FR = time until GS decreased to 50% of maximum during sustained contraction) and grip work (GW = area under the strength-time curve)). The Eforto® system consists of a rubber bulb that is wirelessly connected to a smartphone-based application, and a telemonitoring platform. The aim was to evaluate the validity and reliability of Eforto® to measure muscle fatigability. METHODS: Community-dwelling older persons (n = 61), geriatric inpatients (n = 26) and hip fracture patients (n = 25) were evaluated for GS and muscle fatigability. In community dwellers fatigability was tested twice in the clinic (once with Eforto®, once with Martin Vigorimeter (MV), standard analog handgrip system) and for six consecutive days as a self-assessment at home with Eforto®. In hospitalized participants, fatigability was tested twice using Eforto®, once by a researcher and once by a health professional. RESULTS: Criterion validity was supported by good to excellent correlations between Eforto® and MV for GS (r = 0.95) and muscle fatigability (FR r = 0.81 and GW r = 0.73), and no significant differences in measurements between both systems. Inter-rater and intra-rater reliability for GW were moderate to excellent (intra-class correlation: 0.59-0.94). The standard error of measurement for GW was small for geriatric inpatients and hip fracture patients (224.5 and 386.5 kPa*s) and higher for community-dwellers (661.5 kPa*s). DISCUSSION/CONCLUSION: We established the criterion validity and reliability of Eforto® in older community-dwelling persons and hospitalized patients, supporting the implementation of Eforto® for (self-)monitoring of muscle fatigability.

Hearing aid use and gender differences in the auditory-cognitive cascade in the oldest old.

OBJECTIVES: This study analyzed cognitive differences between hearing-aid (HA) and non-HA users. We hypothesized that HA-use attenuates the auditory-cognitive cascade, thereby, the latter is more conspicuous in non-HA users. Since hearing impairment (HI) shows male predominance, we hypothesized gender differences within the auditory-cognitive relationship. METHODS: Non-frail community-dwellers ≥ 80 years were assessed for HI (pure tone audiogram-PTA; speech reception threshold-SRT) and global and domain-specific cognitive impairments (Mini-Mental State Examination-MMSE; Montreal Cognitive Assessment-MOCA; Reaction Time Test-RT1-4). Pearson and partial correlations (correcting for age and PTA) assessed auditory-cognitive associations within gender and HA subgroups. Fisher's z test compared correlations between HA and non-HA users. RESULTS: 126 participants (age range 80-91 years) were included. HA-use prevalence was 21%. HA-users were older with worse HI (mean PTA 49.5dBHL). HA-users exhibited no significant auditory (PTA, SRT) and cognitive (MMSE, MOCA, RT1- RT4) correlations. Male non-HA users, displayed a significant association between HI and global cognition, processing speed, selective and alternating attention. Significant differences were noted between MMSE and PTA and SRT (z-score 2.28, 3.33, p = 0.02, <0.01, respectively) between HA and non-HA users. CONCLUSION: Male non-HA users displayed an association between HI and global and domain-specific (processing speed; selective and alternating attention) cognitive decline. Associations between global cognition and HI were significantly different between HA and non-HA users. This may be partially attributable to underlying subgroups sample sizes and statistical power disparity. If larger scale longitudinal or interventional studies confirm these findings, timely HI assessment and management may be the cornerstone for delaying cognitive decline.

The impact of covid-19 lockdown on the Quality of life, meaningful activities, and frailty in community-dwelling octogenarians: A study in Belgium.

OBJECTIVES: To investigate the impact of COVID-19 lockdown on quality of life (QoL), meaningful daily activities, and (pre)frailty in community-dwelling octogenarians. METHODS: Cross-sectional design with bivariate and multiple linear regression modeling using a stepwise approach examining the level of QoL during the COVID-19 lockdown in a group of 215 community-dwelling octogenarians (Mage = 86.49 ± 3.02). A comprehensive set of biopsychosocial variables (FRAIL scale, general health, engagement in meaningful activities survey, questions on loneliness, and feelings) were used as explaining variables. RESULTS: Particularly, a decrease in daily activities, social activities, and an increase in free times activities were observed, but the decrease in QoL could be explained by the meaningfulness in activities, together with experiencing emptiness in life, taking ≥ 4 medications a day and feeling down or depressed. CONCLUSIONS: We tried to understand which components contribute to and might affect a person's QoL caused by restrictions imposed by the governance and its influence on the lives of the community-dwelling octogenarians. As such, this output could be a baseline for the development of minimally impacting countermeasures during future lockdowns. CLINICAL IMPLICATIONS: Studying lifestyle changes and thus also variables related to QoL during a pandemic, may support policymakers and practitioners to develop relevant interventions.

Impact of COVID-19 on Physical Activity, Fatigue, and Frailty in Community-Dwelling Older Adults: A Cross-Sectional Study.

This study aimed to describe the level of physical activity and its relation to fatigue and frailty during the COVID-19 pandemic in community-dwelling older adults aged 80 years and over. Three hundred and ninety-one older adults (aged 86.5 ± 3.00) completed a survey including physical activity, the Mobility Tiredness scale, and the FRAIL scale. Linear regression analysis was conducted to assess whether the variables age, sex, and physical activity (independent factors) were significantly related to fatigue and frailty. Respectively, 30.5% and 24.7% of the participants reported a decrease in walking and in energy-intensive activities; 25.4% reported increased sedentary behavior. A lower level of physical activity was associated with higher levels of fatigue and increased frailty risk (p < .05), independently from psychological symptoms. These results are important because participants with lower levels of physical activity and more sedentary behavior are more likely to feel fatigued and have higher risk to be frail.

The influence of hypertension management on frailty prevention among older persons aged 65 and over: a systematic review.

BACKGROUND: Frailty and hypertension are interrelated, but it remains unclear whether this relationship is modified by antihypertensive drugs. METHODS AND RESULTS: A systematic review of PubMed and Web of Science databases was performed to review the influence of hypertension management on preventing the occurrence or progression of frailty in older people aged 65 and over. Studies providing information on this association regardless of the study setting, or definition of hypertension and frailty were included. Among the initial 2298 articles identified, 7 were included in the review. Three observational studies assessed the association between frailty and hypertension. Two of them reported no relationship between Aldosterone Antagonists use and frailty prevention. No relationship between BP and incidence frailty after adjustment for hypertension treatment was observed in two other articles. An indirect relationship was reported in the RCTs included. Higher AT11RaAb levels (control group), can lead to a generalized weakness/frailty risk shown by a decrease in grip strength (r = -0.57, p < 0.005) and walking speed (r = - 0.47, p < 0.005). No significant differences between int-hypertensive intervention and control were observed in frailty status after a 12-weeks follow-up after applying three different frailty measurement tools in the other RCT. CONCLUSIONS: Based on the results of this systematic review we conclude that BP and frailty occur together but whether the treatment with anti-hypertensive drugs modifies this relationship remains unclear and needs to be further investigated.

Does psychological resilience mediate the relation between daily functioning and prefrailty status?

OBJECTIVES: Understanding of prefrailty's relationship with limitations in activities of daily living (ADLs) moderated by psychological resilience is needed, as resilience might support ADLs' maintenance and thus protect against frailty. Therefore, this study aims to analyze the influence of psychological resilience (using the Connor-Davidson Resilience Scale; CD-RISC) on the relation between ADLs and frailty status of older individuals (i.e. prefrail versus robust). DESIGN: Cross-sectional design. SETTING: UZ Brussels, Belgium. PARTICIPANTS: Robust (Fried 0/4;n = 214; Age = 82.3 ± 2.1yrs) and prefrail (Fried 1-2/4; n = 191; Age = 83.8 ±3.2yrs) community-dwelling older individuals were included. MEASUREMENTS: Frailty scores were obtained from weight loss, exhaustion, gait speed, and grip strength. A total Disability Index (DI) expressed dependency for basic (b-), instrumental (i-), and advanced (a-)ADLs. Mediation was investigated by estimating direct and indirect effects of all levels of ADLs and CD-RISC total score on prefrailty/robustness using a stepwise multiple regression approach. RESULTS: Prefrailty/robustness significantly correlated with a-ADL-DI (point-biserial correlation (rpb) = 0.098; p<0.05). Adjusted for age and gender, the a-ADL-DI (p<0.05) had a significant protective direct effect against prefrailty. No effects were found with the CD-RISC total score. CONCLUSIONS: Less limitation in a-ADLs is a directly correlated factor of prefrailty and might represent a higher likelihood of robustness.

Safety and tolerability of 6-month supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink in sarcopenic older adults.

AIMS: Safety and tolerability of prolonged supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink (WP-MND) was evaluated in sarcopenic older adults. METHODS: A 13-week double-blinded, randomized, isocaloric placebo-controlled trial (PROVIDE study; n = 380) was extended with a voluntary 13-week open-label extension (OLE). OLE participants were randomized to receive daily 1 or 2 servings of WP-MND (21 g protein, 3 g leucine, 10 µg vitD and 500 mg calcium per serving). Gastro-intestinal tolerability, kidney function and serum levels of calcidiol, parathyroid hormone (PTH) and calcium were evaluated at week 0, 13 and 26. RESULTS AND DISCUSSION: In response to the high daily protein intake (median1.5; IQR: 1.3, 1.7 g/kg BW/day), the estimated glomerular filtration rate (eGFR) increased in the test group during the RCT (p = 0.013). The same trend was observed for those participants with moderate chronic kidney disease. During OLE no eGFR change was observed in any of the groups. Serum calcidiol and calcium reached a plateau after 13-week WP-MND supplementation. As expected, PTH significantly changed in the opposite direction, decreasing during RCT in the test group (T vs C: p < 0.001) and during OLE in former control groups. During RCT, 20/366 participants with normal baseline calcidiol reached levels ≥ 100 nmol/L (T: n = 18; C: n = 2) and 6 developed albumin-corrected calcium levels > 2.55 mmol/L (T: n = 3; C: n = 3), without associated adverse events. CONCLUSION: A 6 months intervention with up to 2 servings of WP-MND did neither result in kidney function deterioration nor symptoms of vitamin D or calcium toxicity. The product was overall well tolerated.

A Vitamin D, Calcium and Leucine-Enriched Whey Protein Nutritional Supplement Improves Measures of Bone Health in Sarcopenic Non-Malnourished Older Adults: The PROVIDE Study.

Alterations in musculoskeletal health with advanced age contribute to sarcopenia and decline in bone mineral density (BMD) and bone strength. This decline may be modifiable via dietary supplementation. To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of bone health. Participants (n 380) were participants of the PROVIDE study, a 13-week, multicenter, randomized, controlled, double-blind, 2 parallel-group study among non-malnourished older participants (≥ 65 years) with sarcopenia [determined by Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index (SMI; skeletal muscle mass/BW × 100) ≤ 37% in men and ≤ 28% in women using bioelectric impedance analysis] Supplementation of a vitamin D, calcium and leucine-enriched whey protein drink that comprises a full range of micronutrients (active; 2/day) was compared with an iso-caloric control. Serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), biochemical markers of bone formation (osteocalcin; OC, procollagen type 1 amino-terminal propeptide; P1NP) and resorption (carboxy-terminal collagen crosslinks; CTX), insulin like growth factor 1 (IGF-1) and total-body BMD were analysed pre- and post-intervention. Serum 25(OH)D concentrations increased from 51.1 ± 22.9 nmol/L (mean ± SD) to 78.9 ± 21.1 nmol/L in the active group (p < 0.001 vs. control). Serum PTH showed a significant treatment difference (p < 0.001) with a decline in the active group, and increase in the control group. Serum IGF-1 increased in the active group (p < 0.001 vs. control). Serum CTX showed a greater decline in the active group (p = 0.001 vs. control). There were no significant differences in serum OC or P1NP between groups during the intervention. Total body BMD showed a small (0.02 g/cm2; ~ 2%) but significant increase in the active group after supplementation (p = 0.033 vs. control). Consuming a vitamin D, calcium and leucine-enriched whey protein supplement for 13 weeks improved 25(OH)D, suppressed PTH and had small but positive effects on BMD, indicative of improved bone health, in sarcopenic non-malnourished older adults.

Assessment of Muscle Function and Physical Performance in Daily Clinical Practice : A position paper endorsed by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

It is well recognized that poor muscle function and poor physical performance are strong predictors of clinically relevant adverse events in older people. Given the large number of approaches to measure muscle function and physical performance, clinicians often struggle to choose a tool that is appropriate and validated for the population of older people they deal with. In this paper, an overview of different methods available and applicable in clinical settings is proposed. This paper is based on literature reviews performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group on frailty and sarcopenia. Face-to-face meetings were organized afterwards where the whole group could amend and discuss the recommendations further. Several characteristics should be considered when choosing a tool: (1) purpose of the assessment (intervention, screening, diagnosis); (2) patient characteristics (population, settings, functional ability, etc.); (3) psychometric properties of the tool (test-retest reliability, inter-rater reliability, responsiveness, floor and ceiling effects, etc.); (4) applicability of the tool in clinical settings (overall cost, time required for the examination, level of training, equipment, patient acceptance, etc.); (5) prognostic reliability for relevant clinical outcomes. Based on these criteria and the available evidence, the expert group advises the use of grip strength to measure muscle strength and the use of 4-m gait speed or the Short Physical Performance Battery test to measure physical performance in daily practice. The tools proposed are relevant for the assessment of muscle weakness and physical performance. Subjects with low values should receive additional diagnostic workups to achieve a full diagnosis of the underlying condition responsible (sarcopenia, frailty or other).

Six weeks of strength endurance training decreases circulating senescence-prone T-lymphocytes in cytomegalovirus seropositive but not seronegative older women.

BACKGROUND: Ageing is associated with a decline in immune function termed immunosenescence. This process is characterized amongst others by less naive T-cells and more senescent phenotypes, which have been implicated in the pathogenesis of many age-related diseases. Thus far, reports regarding the long-term adaptation effects of exercise on T-cell phenotypes are scant and largely equivocal. These inconsistencies may be due to potential contributors to immunosenescence, particularly cytomegalovirus infection, which is considered a hallmark of T-cell senescence. Therefore, we sought to investigate the impact of cytomegalovirus serostatus on the distribution of peripheral T-cell subsets following long-term exercise in older women. METHODS: One hundred women (aged 65 years and above) were randomized to 3 times/weekly training at either intensive strength training (3 × 10 repetitions at 80% of one-repetition maximum, n = 31), strength endurance training (2 × 30 repetitions at 40% of one-repetition maximum, n = 33), or control (passive stretching exercise, n = 36) for 6 weeks. All training sessions were supervised by trained instructors to minimize the risk of injury and to ensure that the participants adhered to the training protocol throughout the entire range of motion. The T-cell percentages and absolute blood counts were determined before and after 6 weeks (24 h-48 h after the last training session) using flow cytometry and a haematology analyser. Cytomegalovirus antibodies were measured in serum using Architect iSystem and cytomegalovirus serostatus was balanced in the three intervention groups. C-reactive protein was measured using immunonephelometry. RESULTS: We report for the first time that 6 weeks of strength endurance training significantly decreased senescence-prone T-cells along with a small increase in the number of CD8- naive T-cells in blood. The absolute counts of senescent-like T-cells decreased by 44% (from 26.03 ± 35.27 to 14.66 ± 21.36 cells/µL, p < 0.01) and by 51% (from 6.55 ± 12.37 to 3.18 ± 6.83 cells/µL, p < 0.05) for the CD8+ and CD8- T-cell pools, respectively. Intriguingly, these changes were observed in cytomegalovirus seropositive, but not cytomegalovirus seronegative individuals. CONCLUSIONS: In conclusion, the present study shows that strength endurance training leads to a reduction in circulating senescence-prone T-cells in cytomegalovirus seropositive older women. It remains to be established if monitoring of peripheral senescence-prone T-cells may have utility as cellular biomarkers of immunosenescence.

Thirteen weeks of supplementation of vitamin D and leucine-enriched whey protein nutritional supplement attenuates chronic low-grade inflammation in sarcopenic older adults: the PROVIDE study.

BACKGROUND: A chronic low-grade inflammatory profile (CLIP) is associated with sarcopenia in older adults. Protein and Vitamin (Vit)D have immune-modulatory potential, but evidence for effects of nutritional supplementation on CLIP is limited. AIM: To investigate whether 13 weeks of nutritional supplementation of VitD and leucine-enriched whey protein affected CLIP in subjects enrolled in the PROVIDE-study, as a secondary analysis. METHODS: Sarcopenic adults (low skeletal muscle mass) aged ≥ 65 years with mobility limitations (Short Physical Performance Battery 4-9) and a body mass index of 20-30 kg/m2 were randomly allocated to two daily servings of active (n = 137, including 20 g of whey protein, 3 g of leucine and 800 IU VitD) or isocaloric control product (n = 151) for a double-blind period of 13 weeks. At baseline and after 13 weeks, circulating interleukin (IL)-8, IL-1 receptor antagonist (RA), soluble tumor-necrosis-factor receptor (sTNFR)1, IL-6, high-sensitivity C-reactive protein, pre-albumin and 25-hydroxyvitamin(OH)D were measured. Data-analysis included repeated measures analysis of covariance (corrected for dietary VitD intake) and linear regression. RESULTS: IL-6 and IL-1Ra serum levels showed overall increases after 13 weeks (p = 0.006 and p < 0.001, respectively). For IL-6 a significant time × treatment interaction (p = 0.046) was observed, with no significant change over time in the active group (p = 0.155) compared to control (significant increase p = 0.012). IL-8 showed an overall significant decrease (p = 0.03). The change in pre-albumin was a significant predictor for changes in IL-6 after 13 weeks. CONCLUSIONS: We conclude that 13 weeks of nutritional supplementation with VitD and leucine-enriched whey protein may attenuate the progression of CLIP in older sarcopenic persons with mobility limitations.