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Hyperhomocysteinemia induces oxidative stress and chronic inflammation (both of which are catabolic to bone and muscle); thus, we examined the association between homocysteine and body composition and physical function in middle-aged and older adults. Data from the National Health and Nutrition Examination Survey was used to build regression models. Plasma homocysteine (fluorescence immunoassay) was used as the exposure and bone mineral density (BMD; dual-energy X-ray absorptiometry; DXA), lean mass (DXA), knee extensor strength (isokinetic dynamometer; newtons) and gait speed (m/s) were used as outcomes. Regression models were adjusted for confounders (age, sex, race/Hispanic origin, height, fat mass %, physical activity, smoking status, alcohol intakes, cardiovascular disease, diabetes, cancer and vitamin B12). All models accounted for complex survey design by using sampling weights provided by NHANES. 1480 adults (median age: 64 years [IQR: 56, 73]; 50.3% men) were included. In multivariable models, homocysteine was inversely associated with knee extensor strength (β = 0.98, 95% CI 0.96, 0.99, p = 0.012) and gait speed (β = 0.85, 95% CI 0.78, 0.94, p = 0.003) and borderline inversely associated with femur BMD (β = 0.84, 95% CI 0.69, 1.03, p = 0.086). In the sub-group analysis of older adults (≥ 65 years), homocysteine was inversely associated with gait speed and femur BMD (p

Osteoporosis is underdiagnosed and undertreated in people living in Residential Aged Care Facilities (RACFs), even though aged-care residents are at greater risk of experiencing fractures than their community-dwelling counterparts. The first (2009) and second (2016) Consensus Conferences on the Treatment of Osteoporosis in RACFs in Australia addressed the prevention of falls and fractures in RACFs. A third Consensus Conference was held to review advances in the field of osteoporosis for people living in RACFs and to update current guidelines. The Conference was held virtually in October 2020 due to the COVID-19 pandemic. Attendance at the meeting was open to health practitioners (n = 116) (eg, general practitioners, geriatricians, rehabilitation specialists, endocrinologists, pharmacists, and physiotherapists) working in RACFs. Participants chose and/or were assigned to breakout groups to review the evidence and reach a consensus on the topic area assigned to the group, which was then presented to the entire group by a nominated spokesperson. Recommendations developed by breakout groups were discussed and voted on by all attending participants. This article updates the evidence for preventing falls and fractures and managing osteoporosis in older adults living in RACFs based on agreed outcomes from the group. We anticipate these updated recommendations will provide health practitioners with valuable guidance when practicing in RACFs.

PurposeTo compare the diagnostic value of relative sit-to-stand muscle power with grip strength or gait speed for identifying a history of recurrent falls and fractures in older adults.MethodsData from an outpatient clinic included anthropometry (height/weight), bone density, 5 times sit-to-stand time (stopwatch and standardized chair), grip strength (hydraulic dynamometer), and gait speed (4 m). Relative sit-to-stand muscle power (W.kg−1, normalised to body mass) was calculated using a validated equation. Outcomes of falls (past 1 year) and fractures (past 5 years) were self-reported and verified by medical records wherever possible. Binary logistic regression considering for potential confounders (age, sex, BMI, Charlson comorbidity index, femoral neck bone density) and receiver operating characteristics (ROC) curves were used in statistical analysis.Results508 community-dwelling older adults (median age: 78 years, interquartile range: 72, 83, 75.2% women) were included. Compared to greater relative sit-to-stand muscle power (1.62–3.78W.kg−1 for women; 2.03–3.90W.kg−1 for men), those with extremely low relative sit-to-stand muscle power were 2.35 (95% CI 1.54, 3.60, p ConclusionRelative sit-to-stand muscle power performed slightly (but not statistically) better than grip strength or gait speed for identifying a history of recurrent falls and fractures in older adults. However, all tests showed low diagnostic power.

Background Markers of bone metabolism have been associated with muscle mass and function. Whether serum cross-linked C-terminal telopeptides of type I collagen (CTX) is also associated with these measures in older adults remains unknown. Methods In community-dwelling older adults at high risk of falls and fractures, serum CTX (biochemical immunoassays) was used as the exposure, while appendicular lean mass (dual-energy x-ray absorptiometry) and muscle function (grip strength [hydraulic dynamometer], short physical performance battery [SPPB], gait speed, sit-to-stand, balance, Timed Up and Go [TUG]) were used as outcomes. Potential covariates including demographic, lifestyle, and clinical factors were considered in statistical models. Areas under the receiver operating characteristic (ROC) curves were calculated for significant outcomes. Results Two hundred and ninety-nine older adults (median age: 79 years, interquartile range: 73, 84; 75.6% women) were included. In multivariable models, CTX was negatively associated with SPPB (β = 0.95, 95% confidence interval [CI]: 0.92, 0.98) and balance (β = 0.92, 0.86, 0.99) scores, and positively associated with sit-to-stand (β = 1.02, 95% CI: 1.00, 1.05) and TUG (β = 1.03, 95% CI: 1.00, 1.05). Trend line for gait speed (β = 0.99, 95% CI: 0.98, 1.01) was in the hypothesized direction but did not reach significance. Area under the ROC curves showed low diagnostic power ( Conclusions In older adults, higher CTX levels were associated with poorer lower-limb muscle function (but showed poor diagnostic power for these measures). These clinical data build on the biomedical link between bone and muscle.

Background Increasing protein intake (above the Recommended Dietary Amount) alone or with resistance‐based exercise is suggested to improve cardiometabolic health; however, randomized controlled trials (RCTs) are needed to confirm this. Methods The Liverpool Hope University‐Sarcopenia Aging Trial (LHU‐SAT) was a 16 week RCT (ClinicalTrials.gov Identifier: NCT02912130) of 100 community‐dwelling older adults [mean age: 68.73 ± 5.80 years, body mass index: 27.06 ± 5.18 kg/m2 (52% women)] who were randomized to four independent groups [Control (C), Exercise (E), Exercise + Protein (EP), Protein (P)]. E and EP completed supervised and progressive resistance‐based exercise (resistance exercise: two times per week, functional circuit exercise: once per week), while EP and P were supplemented with a leucine‐enriched whey protein drink (three times per day) based on individual body weight (0.50 g/kg/meal, 1.50 g/kg/day). Outcome measures including arterial stiffness (pulse wave velocity), fasting plasma/serum biomarkers [glucose/glycated haemoglobin, total cholesterol, low‐density lipoprotein (LDL), high‐density lipoprotein, insulin, resistin, leptin, adiponectin, C‐reactive protein, tumour necrosis factor‐alpha, interleukin‐6, cystatin‐C, & ferritin], insulin resistance (HOMA‐IR), and kidney function (eGFR) were measured before and after intervention. Results Total protein intake (habitual diet plus supplementation) increased to 1.55 ± 0.69 g/kg/day in EP and to 1.93 ± 0.72 g/kg/day in P, and remained significantly lower (P 0.05), and kidney function (eGFR) remained unaltered. Conclusions Sixteen weeks of leucine‐enriched whey protein supplementation alone and combined with resistance‐based exercise improved cardiometabolic health markers in older adults.

Abstract 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.

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 (β: 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.

To determine whether osteosarcopenia is associated with a greater likelihood of recurrent fractures, as well as type of fracture, than osteopenia/osteoporosis or sarcopenia alone.Anthropometry (height/weight; scales and stadiometer), body composition (bone mineral density [BMD] and appendicular lean mass; dual-energy x-ray absorptiometry), grip strength (hydraulic dynamometer), and gait speed (4 m) were measured in an outpatient clinic. WHO definition for osteopenia/osteoporosis (BMD T-score below -1 SDs) while sarcopenia was defined by SDOC or EWGSOP2. Number and location of fractures within the past 5 years were self-reported and verified by medical records (unverified fractures excluded). Univariable and multivariable regressions were used to examine the association between the exposure and outcome while adjusting for confounders.481 community-dwelling older adults (median age: 78, IQR: 72, 83; 75.9% women) were included. Prevalence of osteosarcopenia depended on the definition (SDOC: 179 (37.2%); EWGSOP2: 123 (25.6%)). In multivariable analysis adjusting for age, sex, alcohol, smoking, BMI, lowest BMD T-score, physical activity, and comorbidities, the likelihood of recurrent fractures (≥ 2 vs 0-1) was significantly higher in those with osteosarcopenia versus osteopenia/osteoporosis irrespective of the definition (SDOC: odds ratio [OR]: 1.63, 95% CI: 1.03, 2.59, p = 0.037; EWGSOP2: OR: 1.83, 95% CI: 1.12, 3.01, p = 0.016]. Associations with sarcopenia alone (SDOC: 10; EWGSOP2: 7) were not possible due to the extremely low prevalence of this condition in those with normal BMD.Our data suggest osteosarcopenia is associated with a greater likelihood of recurrent fractures versus osteopenia/osteoporosis alone. Further studies are needed to evaluate the relationship with sarcopenia alone.

Objectives Sarcopenia Definitions and Outcomes Consortium (SDOC) provides cut-points based on muscle weakness (low grip strength) and slowness (poor gait speed) for low-risk populations; however, it is unknown if these criteria apply to high-risk populations. We examined the association between SDOC criteria and important health status indicators in high-risk older persons. Design Cross-sectional study. Setting and Participants 356 community-dwelling older persons (median age: 79 years, interquartile range: 73, 83; 75.2% women) attending a falls and fractures clinic in Melbourne, Australia. Methods Grip strength (hydraulic dynamometer) and gait speed (over 4 m) were used to define sarcopenia using SDOC cut-points. Health measures included falls (past 1 year) and fractures (past 5 years) by self-report, and malnutrition, depression, balance confidence, fear of falling, static balance (limits of stability), dynamic balance (Four-Square Step Test), and body composition [body mass index and lean mass, fat mass, and bone density (via dual-energy x-ray absorptiometry)] were assessed using validated procedures. Fasting vitamin D and parathyroid hormone concentrations were measured by immunoassays. Participants were categorized as nonsarcopenic or sarcopenic based on the SDOC cut-points, and multivariate models were used to examine the association between sarcopenia and health status indicators while adjusting for confounding factors. Results After adjusting for covariates, sarcopenic older persons (n = 162, 45.5%) were positively associated with malnutrition [odds ratio (OR) 3.21, 95% confidence interval (CI) 1.63, 6.32], depression (OR 4.11, 95% CI 2.31, 7.29), fear of falling (OR 1.08, 95% CI 1.06, 1.10) as well as recurrent (2 or more) falls (OR 1.62, 95% CI 1.01, 2.59) and fractures (OR 2.26, 95% CI 1.17, 4.36), and negatively associated with poor balance confidence (OR 0.96, 95% CI 0.95, 0.97) (P Conclusions and Implications SDOC criteria are strongly associated with important health status indicators in high-risk older persons, which strengthens the clinical utility of the SDOC in these populations.

Osteoporosis and sarcopenia are common in older adults. Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Bone fractures can result in changes in posture, pain, the need for surgical repair and functional impairment. Sarcopenia is the progressive and generalized loss of skeletal muscle mass, strength and/or physical performance. Older adults with sarcopenia experience increased risk of frailty, disability, hospitalizations, mortality, and a reduced quality of life. In this narrative review we provide guidance regarding the prevention of both osteoporosis and sarcopenia, including interventions that prevent both conditions from occurring, recommended screening and treatment to prevent progression.

Two mechanisms implicated in telomere shortening are oxidative stress and inflammation, both of which are linked to bone and muscle loss suggesting a pathological link between telomere attrition and osteosarcopenia. Using older adults aged 60 years and over in the UK Biobank, we examined the association between leukocyte telomere length and osteosarcopenia.Baseline leukocyte telomere length was measured using a multiplex qPCR technique and expressed as the amount of the telomere amplification product (T) to that of a single-copy gene (S) (T/S ratio). Osteosarcopenia data was from the first imaging visit and defined by WHO criteria (femoral neck bone density T score ≤ -1) for osteopenia/osteoporosis plus either the EWGSOP2 (low appendicular lean mass/heightAmong 20,400 older adults (mean age: 67.79 ± 4.9 years, 53% men), the prevalence of osteosarcopenia by EWGSOP2 (n = 96, 0.47%) or SDOC (n = 205, 1%) criteria was low at the first imaging visit (mean 8.82 years after baseline). Baseline telomere length was not associated with osteosarcopenia by EWGSOP2 (Relative Risk (RR): 1.00, 95% CI: 0.82-1.23 comparing osteosarcopenia to normal (non-osteopenic, non-osteoporotic, and non-sarcopenic) per Standard Deviation (SD) increase in telomere length) or SDOC (RR: 0.95, 95% CI: 0.83-1.09) criteria. Longer telomere length was associated with a lower risk of slow walking pace (Odds Ratio: 0.92, 95% CI: 0.87-0.99 per SD increase in telomere length, p = 0.021). Telomere length, however, was not associated with low grip strength, low bone density or low appendicular lean mass/heightIn this population-based study, telomere length was not associated with osteosarcopenia; however, slow walking pace was. Further studies are needed to reexamine this relationship, including a greater number of the oldest-old (≥75 years) where osteosarcopenia is more prevalent.

Advances in medicine have paved the way for older persons to live longer, but with more years spent living with disability and dependency. Many older persons are living with comorbidities such as osteoporosis (loss of bone mass) and sarcopenia (loss of muscle mass and function), two diseases that, when concurrent, form osteosarcopenia, a newly identified musculoskeletal syndrome. Osteosarcopenia impedes mobility and diminishes independence and thus quality of life. Evidence suggests the pathology of this syndrome comprises genetic polymorphisms, alterations in mechanotransduction, and localized or systemic crosstalk between growth factors and other proteins (myokines, osteokines, adipokines). As a direct result of an aging society, health outcomes such as falls and fractures will rise as the prevalence of osteosarcopenia increases. Two major risk factors for osteosarcopenia (other than age itself) are physical inactivity and poor nutrition. Addressing these modifiable risk factors can prevent, or at least delay, the onset of osteosarcopenia. Pharmaceutical treatments for osteosarcopenia are currently unavailable, although research trials are underway. This review provides an update from basic and clinical sciences on the biology, epidemiology (prevalence, risk factors and diagnosis) and treatments for osteosarcopenia, and recommends future research priorities to improve health outcomes for those living with or at risk of osteosarcopenia.

OBJECTIVE: To examine the effects of protein supplementation on muscle mass, strength and function in individuals at risk of muscle wasting disorders. METHODS: A narrative overview of the literature based on a PubMed search. RESULTS: Increasing protein intake beyond the recommended dietary intake may prevent or attenuate muscle loss in people at risk of muscle wasting disorders; however, there is inconsistent evidence for any benefits on muscle strength or physical function. This is likely due to the significant heterogeneity and bias regarding baseline demographics, basal protein/energy intakes and protein supplement type, dose, timing and compliance. CONCLUSION: Protein supplementation attenuates muscle loss in some populations at increased risk of muscle wasting, but there is no consistent evidence to support benefits on muscle strength or physical function. Further randomised controlled trials are needed that focus on whether there is an optimal type, dose and timing of protein intake, and potential interaction with other nutrients.

To summarize current evidence on osteosarcopenia. Knowledge on osteosarcopenia as a geriatric syndrome is growing. This will facilitate the development of robust biomarkers and new treatments with dual effect on muscle and bone. When assessing older persons for osteoporosis, concomitant assessment for sarcopenia (and vice versa) should be included as an essential part of the comprehensive geriatric assessment. Osteosarcopenia is a geriatric syndrome characterized by declines in bone density and microarchitecture and muscle mass and strength, which has gained clinical interest due to its association with falls and fragility fractures. This review discusses the epidemiology of osteosarcopenia including clinical assessment, the pathophysiological aspects leading to the loss of muscle and bone mass, and efficacious therapeutic strategies to combat this syndrome. The etiology of osteosarcopenia is thought to include genetic and environmental factors which interact with muscle and bone at the cellular level, reinforcing that these tissues are interconnected not only by mechanical aspects, but also by humoral factors. Osteosarcopenia is identified by low muscle and bone mass and impaired strength of these tissues via imaging and physical performance measures. The diagnosis of osteosarcopenia is of clinical importance since early interventions, particularly resistance exercise, and adequate intake of protein, vitamin D and calcium, may delay the onset of individual components (osteopenia/sarcopenia) of osteosarcopenia.

We sought to examine the associations of osteosarcopenia with physical performance, balance, and falls and fractures in community-dwelling older adults. Additionally, we aimed to determine which clinical outcomes are associated with specific components of osteosarcopenia.Cross-sectional study.253 participants (77% women; aged 77.9 ± 0.42 years) who presented for a falls and fractures risk assessment in Melbourne, Australia.Participants were mobile, community-dwelling older adults (≥65 years) free of cognitive impairment. Body composition (via dual-energy x-ray absorptiometry), physical performance [via Timed Up and Go (TUG) and Short Physical Performance Battery (SPPB)], and balance [via Four-Square Step test (FSS) and posturography] were examined. Falls in the past year and fractures in the past 5 years were self-reported. Osteosarcopenia was defined as (1) low bone mineral density (BMD) [T score-1 standard deviation (SD)] combined with sarcopenia and (2) osteoporosis (BMD T score ≤-2.5 SD) combined with severe sarcopenia. For sarcopenia, we employed the criteria of the European Working Group on Sarcopenia in Older People (EWGSOP1), the revised criteria (EWGSOP2), and that of the Foundation for the National Institutes for Health (FNIH). Kruskal-Wallis and logistic regression tests were used for statistical analysis.Osteosarcopenia was associated with worse SPPB, TUG, FSS, limit of stability, and falls and fractures history. Additionally, osteosarcopenia (using the severe sarcopenia classification) conferred an increased rate of falls [odds ratios (ORs) from 2.83 to 3.63; P .05 for all] and fractures (ORs from 3.86 to 4.38; P .05 for all) when employing the EWGSOP2 and FNIH definitions, respectively.Compared with the nonosteosarcopenic group, those with osteosarcopenia had greater impairment of physical performance and balance. The EWGSOP2 and FNIH criteria resulted in the strongest associations with physical performance and self-reported falls and fractures.

To investigate the effects of exercise in combination with, or without, a leucine-enriched whey protein supplement on muscle mass, fat mass, myoelectrical muscle fatigue and health-related quality of life (HR-QOL) in older adults. 100 community-dwelling older adults [52% women, age: 69 ± 6 years (mean ± SD)] were randomised to four [Control (C); Exercise (E); Exercise + Protein (EP); Protein (P)] independent groups. E and EP groups completed 16 weeks of exercise [resistance (2 times/week) and functional (1 time/week]. EP and P groups were also administered a leucine-enriched whey protein supplement (3 times/day) based on body weight (1.5 g/kg/day). Muscle and fat mass (bioelectrical impedance analysis), myoelectrical muscle fatigue (surface electromyography) and HR-QOL (WHOQOL-BREF) were measured pre- and post-intervention. At post-intervention, the rectus femoris (E: − 4.8%/min, p = 0.007, ES = 0.86; EP: − 3.3%/min, p = 0.045, ES = 0.58) and bicep femoris (E: − 3.9%/min, p 0.05). Physical exercise is a potent method to improve myoelectrical muscle fatigue and HR-QOL in older adults. However, leucine-enriched whey protein did not augment this response in those already consuming sufficient quantities of protein at trial enrolment.

Methods The aim of this paper is to define terms commonly related to sarcopenia to enable standardization of these terms in research and clinical settings. The Global Leadership Initiative in Sarcopenia (GLIS) aims to bring together leading investigators in sarcopenia research to develop a single definition that can be utilized worldwide; work on a global definition of sarcopenia is ongoing. The first step of GLIS is to develop the common terminology, or a glossary, that will facilitate agreement on a global definition of sarcopenia as well as interpretation of clinical and research findings. Results Several terms that are commonly used in sarcopenia research are defined, including self-reported measures of function and ability; objective physical performance tests; and measures related to muscle function and size. Conclusion As new methods and technologies are developed, these definitions may be expanded or refined over time. Our goal is to promote this common language to describe sarcopenia and its components in clinical and research settings in order to increase clinical awareness and research interest in this important condition. We hope that the use of common terminology in sarcopenia research will increase understanding of the concept and improve communication around this important age-related condition. Key summary points Aim The aim of this paper is to define terms commonly related to sarcopenia to enable standardization of these terms in research and clinical settings. Findings This paper provides definitions for commonly used terminology in sarcopenia in both clinical and research settings. As new methods and technologies are developed, this terminology may be expanded or refined over time. Message We hope that the use of common terminology in sarcopenia research will increase understanding of the concept and improve communication around this important age-related condition.

IntroductionImmunosenescence leads to increased morbidity and mortality associated with viral infections and weaker vaccine responses. This has been well documented for seasonal influenza and the current pandemic with Sars-Cov2, which disproportionately impact older adults, particularly those in residential aged care facilities. Inadequate nutrient intake associated with impaired immunity, respiratory and muscle function are likely to augment the effects of immunosenescence. In this study, we test whether the effects of inadequate nutrition can be reversed by multi-nutrient supplementation, consequently enhancing vaccine responses, reducing the risk of viral infections, and improving respiratory and muscle function.Methods and analysisThe Pomerium Study is a 12-week, single-blinded, randomised, placebo-controlled trial testing the effects of two daily servings of an oral multi-nutrient supplement (330 kcal, 20g protein, 1.2g CaHMB, 449mg calcium, 520IU vitamin D3, and 25 vitamins and minerals) on the immune system and muscle and respiratory function of older adults in aged-care in Melbourne, Australia. 160 older adults (≥75 years old) will be recruited from aged-care facilities and randomised to treatment (multi-nutrient supplement) or control (usual care). Primary outcome is the change in T-cell subsets CD8+ and CD28null counts at 4 and 12 weeks post-intervention. Secondary outcomes measured at baseline and after 12 weeks post-intervention are multiple markers of immunosenescence, body composition (bioimpedance), handgrip strength (dynamometer), physical function (short physical performance battery), respiratory function (spirometry), and quality of life (EQ-5D-3L). Incidence and complications of COVID-19 and/or viral infections (i.e., hospitalisation, complications, or death) will be recorded throughout the trial.DiscussionIf the Pomerium Study demonstrates efficacy and safety of a multi-nutrient supplement on immune, muscle and respiratory function, it may be suitable as a strategy to reduce the adverse outcomes from seasonal influenza and viral infections such as COVID-19 in older adults in aged-care.Funding, Ethics, Registration and DisseminationThe study is funded by the Australian Medical Research Future Fund. It is approved by Melbourne Health Human Research Ethics Committee (Ref No. HREC/73985/MH-2021, ERM Ref No. RMH73985, Melbourne Health Site Ref No. 2021.115), and registered at ANZCTR (12621000420842). Results will be published in peer-reviewed journals and made available to aged-care stakeholders, including providers, residents, and government bodies.Article Summary Strengths and LimitationsThis is the first study performing a comprehensive immune, respiratory and functional assessment in aged care residents after receiving a multi-nutrient solution that is commercially available.Our design and tested intervention assure that the results of the study will be rapidly translated into practice.The main limitation is that any biological effect observed cannot be attributed to one component of the multi-nutrient supplement.Another limitation is that the potential effect of group differences in energy intake on outcomes can only be monitored by assessing regular dietary intake and weight changes during the study period.

Background: Metabolic Syndrome (MetS) is a cluster of risk factors for diabetes and cardiovascular diseases with pathophysiology strongly linked to aging. A range of circulatory metabolic biomarkers such as inflammatory adipokines have been associated with MetS, however, the diagnostic power of these markers as MetS risk correlates in elderly has yet to be elucidated. This cross-sectional study investigated the diagnostic power of circulatory metabolic biomarkers as MetS risk correlates in older adults. Methods: Hundred community dwelling older adults (mean age: 68.7 years) were recruited in a study, where their blood pressure, body composition and Pulse Wave Velocity (PWV) were measured, and their fasting capillary and venous blood were collected. The components of the MetS, and the serum concentrations of Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), Plasminogen Activator Inhibitor-I (PAI-I), Leptin, Adiponectin, Resistin, Cystatin-C, C-Reactive Protein (CRP), insulin and ferritin were measured within the laboratory, and the HOMA1-IR and Atherogenic Index of Plasma (AIP) were calculated. Results: Apart from other markers which were related with some cardiometabolic (CM) risk, after Bonferroni correction insulin had significant association with all components of Mets and AIP. These associations also remained significant in multivariate regression. The multivariate odds ratio (OR with 95% confidence interval (CI)) showed a statistically significant association between IL-6 (OR: 1.32 (1.06–1.64)), TNF-α (OR: 1.37 (1.02–1.84)), Resistin (OR: 1.27 (1.04–1.54)) and CRP (OR: 1.29 (1.09–1.54)) with MetS risk, however, these associations were not found when the model was adjusted for age, dietary intake and adiposity. In unadjusted models, insulin was consistently statistically associated with at least two CM risk factors (OR: 1.33 (1.16–1.53)) and MetS risk (OR: 1.24 (1.12–1.37)) and in adjusted models it was found to be associated with at least two CM risk factors and MetS risk (OR: 1.87 (1.24–2.83) and OR: 1.25 (1.09–1.43)) respectively. Area under curve (AUC) for receiver operating characteristics (ROC) demonstrated a good discriminatory diagnostics power of insulin with AUC: 0.775 (0.683–0.866) and 0.785 by cross validation and bootstrapping samples for at least two CM risk factors and AUC: 0.773 (0.653–0.893) and 0.783 by cross validation and bootstrapping samples for MetS risk. This was superior to all other AUC reported from the ROC analysis of other biomarkers. Area under precision-recall curve for insulin was also superior to all other markers (0.839 and 0.586 for at least two CM risk factors and MetS, respectively). Conclusion: Fasting serum insulin concentration was statistically linked with MetS and its risk, and this link is stronger than all other biomarkers. Our ROC analysis confirmed the discriminatory diagnostic power of insulin as CM and MetS risk correlate in older adults.

Purpose To evaluate the effects of probiotic supplementation on gastrointestinal (GI) symptoms, circulatory markers of GI permeability, damage, and markers of immune response during a marathon race. Methods Twenty-four recreational runners were randomly assigned to either supplement with a probiotic (PRO) capsule [25 billion CFU Lactobacillus acidophilus (CUL60 and CUL21), Bifidobacterium bifidum (CUL20), and Bifidobacterium animalis subs p. Lactis (CUL34)] or placebo (PLC) for 28 days prior to a marathon race. GI symptoms were recorded during the supplement period and during the race. Serum lactulose:rhamnose ratio, and plasma intestinal-fatty acid binding protein, sCD14, and cytokines were measured pre- and post-races. Results Prevalence of moderate GI symptoms reported were lower during the third and fourth weeks of the supplement period compared to the first and second weeks in PRO (p 0.05). During the marathon, GI symptom severity during the final third was significantly lower in PRO compared to PLC (p = 0.010). The lower symptom severity was associated with a significant difference in reduction of average speed from the first to the last third of the race between PLC (− 14.2 ± 5.8%) and PRO (− 7.9 ± 7.5%) (p = 0.04), although there was no difference in finish times between groups (p > 0.05). Circulatory measures increased to a similar extent between PRO and PLC (p > 0.05). Conclusion Probiotics supplementation was associated with a lower incidence and severity of GI symptoms in marathon runners, although the exact mechanisms are yet to be elucidated. Reducing GI symptoms during marathon running may help maintain running pace during the latter stages of racing.

IntroductionImmunosenescence leads to increased morbidity and mortality associated with viral infections and weaker vaccine responses. This has been well documented for seasonal influenza and the current pandemic with SARS-CoV-2 (COVID-19), which disproportionately impact older adults, particularly those in residential aged care facilities. Inadequate nutrient intakes associated with impaired immunity, respiratory and muscle function are likely to augment the effects of immunosenescence. In this study, we test whether the impact of inadequate nutrition can be reversed using multi-nutrient supplementation, consequently enhancing vaccine responses, reducing the risk of viral infections and improving respiratory and muscle function.Methods and analysisThe Pomerium Study is a 3-month, single-blind, randomised, controlled trial testing the effects of two daily servings of an oral multi-nutrient supplement (330 kcal, 20 g protein, 1.5 g calcium 3-hydroxy-3-methylbutyrate monohydrate (CaHMB), 449 mg calcium, 500 IU vitamin D3 and 25 vitamins and minerals) on the immune system and muscle and respiratory function of older adults in aged care in Melbourne, Australia. 160 older adults (≥75 years old) will be recruited from aged care facilities and randomised to treatment (multi-nutrient supplement) or control (usual care). The primary outcome is a change in T-cell subsets CD8 + and CD28null counts at months 1 and 3. Secondary outcomes measured at baseline and month 3 are multiple markers of immunosenescence (also at 1 month), body composition (bioimpedance), handgrip strength (dynamometer), physical function (short physical performance battery), respiratory function (spirometry) and quality of life (EQ-5D-5L). Incidence and complications of COVID-19 and/or viral infections (ie, hospitalisation, complications or death) will be recorded throughout the trial, including 3 months after supplementation is ceased.Ethics and disseminationThis study was approved by Melbourne Health Human Research Ethics Committee (Ref No. HREC/73985/MH-2021, ERM Ref No. RMH73985, Melbourne Health Site Ref No. 2021.115). Written informed consent will be obtained from participants. Results will be published in peer-reviewed journals and made available to key aged care stakeholders, including providers, residents, and government bodies.Trial registration numberACTRN12621000420842.

Osteosarcopenia is a geriatric syndrome defined by the concomitant presence of osteopenia/osteoporosis (loss of bone mineral density (BMD)) and sarcopenia (loss of muscle mass and/or function), which increases the risk of falls, fractures, and premature mortality. To examine the efficacy of non-pharmacological (exercise and/or nutritional) interventions on musculoskeletal measures and outcomes in osteosarcopenic adults by reviewing findings from randomized controlled trials (RCTs). This review was registered at PROSPERO (registration number: CRD42020179292) and conducted in accordance with the PRISMA guidelines. Electronic databases were searched for RCTs assessing the effect of at least one non-pharmacological intervention (any form of exercise and/or supplementation with protein, vitamin D, calcium or creatine) on any musculoskeletal measure/outcome of interest (BMD, bone strength/turnover, muscle mass and strength, physical performance, falls/fractures) in adults with osteosarcopenia as defined by any proposed criteria. Two RCTs (of n=106 older osteosarcopenic adults (≥65 years)) assessing the effects of progressive resistance training (RT) (via resistance bands or machines; 2–3 times/week; ∼60 minutes in duration) were eligible for inclusion. The two RCTs demonstrated moderate quality evidence that RT increases muscle mass, strength, and quality, with changes in strength and quality occurring before muscle mass (12 vs 28 weeks). There was low quality evidence that RT increases lumbar spine BMD and maintains total hip BMD when performed for 12 and 18 months, respectively, and moderate quality evidence that RT has no effect on markers of bone turnover or physical performance. No major adverse effects were recorded in either of the RCTs. There were no eligible RCTs examining the impact of nutritional interventions. Chronic RT is safe and effective at potentiating gains in muscle mass, strength, and quality, and increasing or maintaining BMD in older osteosarcopenic adults. No RCT has examined the effects of protein, vitamin D, calcium, or creatine against a control/placebo in this high-risk population.

PURPOSE OF REVIEW: Osteosarcopenia (the joint loss of bone density and muscle mass and function) is an emerging geriatric syndrome, which associates with poor health outcomes. Several nutrients including protein, vitamin D and calcium interact (directly or through absorption properties) to regulate muscle and bone metabolism. We provided an update on the efficacy of these nutrients on musculoskeletal outcomes in older adults with, or at risk of, osteosarcopenia. RECENT FINDINGS: Randomized trials show that correcting vitamin D and calcium deficiencies to meet the recommended dietary allowance (RDA) increases bone density and reduces fracture (but not falls) risk. Supplementing above the RDA with protein supports gains in lean mass and lumbar-spine bone density; however, there is inconclusive evidence for muscle strength, physical function or other bone density sites. A likely explanation for this relates to the significant heterogeneity between trials regarding protein dose, type and timing, as well as baseline protein intake. Further high-quality trials are needed in older osteosarcopenic adults to investigate the effects of protein (while correcting vitamin D and calcium deficiencies) on clinically meaningful outcomes such as activities of daily living, falls and fractures. SUMMARY: An adequate intake of protein (1.2-1.5 g/kg/day), vitamin D (800 IU/day) and calcium (1000-1200 mg/day), is well tolerated and effective at mitigating some aspects of osteosarcopenia such as lean mass, bone density and fracture risk.

Background Sarcopenia is defined as the age-related loss of muscle mass, strength, and physical performance. The original European Working Group on Sarcopenia in Older Persons (EWGSOP1) definition, and its revision (EWGSOP2), provide new cut-points and alternate measures for sarcopenia diagnosis. However, sarcopenia is rarely diagnosed in clinical settings owing to its labor-intensive diagnostic process. Given the Short Physical Performance Battery (SPPB) is a quick, easily administrable, and objective measure of muscle strength and physical performance, both of which are key components of sarcopenia, this study examined the diagnostic value of the SPPB for this muscle disease. Methods A cross-sectional analysis of 294 community-dwelling older persons (≥65 years) was conducted. Appendicular lean body mass [(ALM) divided by height squared (ALM/h2)], muscle strength (handgrip/sit to stand), and physical performance [gait speed, timed up and go (TUG) and SPPB] were assessed using validated procedures, while participants were diagnosed with sarcopenia following the EWGSOP1 and EWGSOP2 criteria. Diagnostic ability of the SPPB independently and combined with ALM/h2 for sarcopenia was determined using area under the curve (AUC). Potential cut-points were identified, and sensitivity and specificity calculated. Results Prevalence of sarcopenia ranged from 4 to 16% depending on the definition. The SPPB demonstrated moderate (AUC = 0.644–0.770) value in diagnosing sarcopenia, and a cut-point of ≤8points in SPPB performance resulted in high sensitivity (82–100%) but low specificity (36–41%) for diagnosing those with severe sarcopenia. Conclusions The SPPB displayed acceptable value in diagnosing older adults with severe sarcopenia. Moreover, the high sensitivity of the SPPB when using the cut-point of ≤8 suggests it may be a favorable screening tool for sarcopenia in clinical settings where ALM measurements are not available.

Skeletal muscle and bone are connected anatomically and physiologically, and play a crucial role in human locomotion and metabolism. Historically, the coupling between muscle and bone has been viewed in light of mechanotransduction, which dictates that the mechanical forces applied to muscle are transmitted to the skeleton to initiate bone formation. However, these organs also communicate through the endocrine system, orchestrated by a family of cytokines namely myokines (derived from myocytes) and osteokines (derived from bone cells). A third player in this biochemical crosstalk is adipose tissue and the secretion of adipokines (derived from adipocytes). In this review, we discuss the bidirectional effects of myokines and osteokines on muscle and bone metabolism, and the impact of adipokines on both of these secretory organs. Several myokines, notably, IL6, irisin, IGF-1, BDNF, myostatin, and FGF2 exert anabolic/catabolic effects on bone, while the osteokines osteocalcin and sclerostin have shown to induce muscle anabolism and catabolism, respectively. Adipokines, such as leptin, resistin, adiponectin, and TNFα (released from adipose tissue), can also modulate muscle and bone metabolism. Contrarily, exercise-mediated release of lipolytic myokines (IL6, irisin, and LIF) stimulates thermogenesis by promoting the browning of adipocytes. Myokines, osteokines, and adipokines exert autocrine/paracrine effects locally as well as through the endocrine system, to regulate muscle, bone, and fat metabolism. Reductions in physical activity and increases in energy intake, both linked with aging, leads to adipocyte hypertrophy and the recruitment of immunological cells (macrophages). In turn, this releases pro-inflammatory adipokines which induces chronic low-grade inflammation (LGI), a key player in the pathology of several diseases. However, exercise-induced stimulation of bioactive cytokines, through muscle-bone-fat crosstalk, increases muscle anabolism, bone formation, mitochondrial biogenesis, glucose utilization, and fatty acid oxidation, and attenuates chronic LGI.

To investigate the association between bone mineral density (BMD) and the severity of sarcopenia using the revised European Working Group on Sarcopenia in Older People (EWGSOP2) definition. Osteoporosis was associated with a greater risk of sarcopenia when using the European definition. Health care professionals should screen for sarcopenia in those with osteoporosis. To investigate the association between bone mineral density (BMD) and the severity of sarcopenia using the revised European Working Group on Sarcopenia in Older People (EWGSOP2) definition. BMD [dual energy X-ray absorptiometry (DXA)], appendicular lean mass (DXA), handgrip strength (hydraulic dynamometer) and gait speed (over 4-m) were used to screen for osteoporosis and sarcopenia. Participants were categorized as osteoporotic according to the World Health Organization definition (T score ≤ − 2.5), and classified with probable sarcopenia or confirmed sarcopenia according to the EWGSOP2 criteria. Fasting biochemistry profile, fragility fractures, malnutrition index, geriatric depression scale and fear of falling, were also measured using validated procedures. A total of 484 community-dwelling older adults (69.6% women) with a median age of 76 years [Interquartile range (IQR) 70–81] were included in this study. Osteoporosis prevalence increased from 47.6% in non-sarcopenia to 65.5% in probable sarcopenia and 78.1% in those with confirmed sarcopenia (p

ObjectiveTo investigate the effects of a 16-week concurrent exercise regimen [resistance exercise (RE) + functional exercise (FE)] in combination with, or without, a leucine-enriched whey protein isolate supplement on muscle strength, physical functioning, aerobic capacity, and cardiometabolic health in older adults (≥60 years). Physical activity levels were also evaluated 6 months post-cessation of the intervention.MethodsForty-six, community-dwelling, previously untrained males, and females [age: 68 ± 5 years (mean ± SD); BMI: 27.8 ± 6.2 kg/m2] who completed the trial were initially randomized to one of two independent arms [Exercise n = 24 (E); Exercise+Protein n = 22 (EP)]. Both arms completed 16 weeks of RE (performed to fatigue) (2 times/week) with FE (1 time/week) on non-consecutive days. Additionally, EP were administered a leucine-enriched whey protein supplement (3 times/day) for 16 weeks based on individual body-weight (1.5 g/kg/day).ResultsAs a result of dietary supplementation, protein intake increased in EP (∼1.2 ± 0.4 to 1.5 ± 0.7 g/kg/day) during the intervention. Maximal strength (1RM) values for leg press (E: +39 ± 7 kg, p = 0.006; EP: +63 ± 7 kg, p < 0.001), chest press (E: +22 ± 4 kg, p < 0.001; EP: +21 ± 6 kg, p < 0.001), and bicep curl (E: +7 ± 0 kg, p = 0.002; EP: +6 ± 1 kg, p = 0.008) significantly increased in E and EP respectively, with no differences between arms (p > 0.05). Physical functioning in the obstacle course (E: -5.1 ± 6.8 s, p < 0.001; EP: -2.8 ± 0.8 s, p < 0.001) and short-physical performance battery scores (E: +0.5 ± 0.5, p = 0.05). No significant change was observed for markers of cardiometabolic health (glycaemic control or blood pressure) (p > 0.05). At follow-up, 86% of older adults reported to performing physical activity ≥1 per week. Of those, 61% were still participating in strength- and cardiovascular- based exercise.ConclusionConcurrent exercise (RE + FE) offers a potent method to combat age-related muscle weakness, and our results suggest a high proportion of older adults may continue to exercise unsupervised. However, leucine-enriched whey protein isolate supplementation did not confer any additional benefit in those already consuming ample amounts of dietary protein at trial enrolment. Future trials should utilize a whole-foods approach and investigate the effects in frail and non-frail older adults habitually consuming the RDA of protein, to assess if a higher intake of protein is needed to delay the onset of muscle weakness.Trial RegistrationClinicaltrials.gov Identifier: NCT02912130.

Sarcopenia is an age-related disease characterized by low muscle mass, strength and function, which associates with falls, fractures, hospitalizations, frailty, disability, and a range of acute and chronic diseases. In turn, inducing astronomical health costs and impeding quality of life. The pathophysiology of sarcopenia is multifactorial with immunological, neurological, nutritional, and physical activity changes all described. Over the past decade, sarcopenia has observed an upsurge of research from basic to translational science, in the hope of developing accurate diagnostic methods, and effective treatments, for this muscle disease. Regarding treatments, physical-activity in the form of resistance exercise remains the most promising strategy, with dietary-protein capable of augmenting this affect. So far, no approved drug treatments exist for sarcopenia, although there are promising findings from animal models. In the coming years, it is expected diagnostic, treatment and preventions options for sarcopenia will form part of clinical care.