MicroRNAs and their Modulatory Effect on the Hallmarks of Osteosarcopenia.

PURPOSE OF THE REVIEW: Osteosarcopenia is a geriatric syndrome associated with disability and mortality. This review summarizes the key microRNAs that regulate the hallmarks of sarcopenia and osteoporosis. Our objective was to identify components similarly regulated in the pathology and have therapeutic potential by influencing crucial cellular processes in both bone and skeletal muscle. RECENT FINDINGS: The simultaneous decline in bone and muscle in osteosarcopenia involves a complex crosstalk between these tissues. Recent studies have uncovered several key mechanisms underlying this condition, including the disruption of cellular signaling pathways that regulate bone remodeling and muscle function and regeneration. Accordingly, emerging evidence reveals that dysregulation of microRNAs plays a significant role in the development of each of these hallmarks of osteosarcopenia. Although the recent recognition of osteosarcopenia as a single diagnosis of bone and muscle deterioration has provided new insights into the mechanisms of these underlying age-related diseases, several knowledge gaps have emerged, and a deeper understanding of the role of common microRNAs is still required. In this study, we summarize current evidence on the roles of microRNAs in the pathogenesis of osteosarcopenia and identify potential microRNA targets for treating this condition. Among these, microRNAs-29b and -128 are upregulated in the disease and exert adverse effects by inhibiting IGF-1 and SIRT1, making them potential targets for developing inhibitors of their activity. MicroRNA-21 is closely associated with the occurrence of muscle and bone loss. Conversely, microRNA-199b is downregulated in the disease, and its reduced activity may be related to increased myostatin and GSK3ß activity, presenting it as a target for developing analogues that restore its function. Finally, microRNA-672 stands out for its ability to protect skeletal muscle and bone when expressed in the disease, highlighting its potential as a possible therapy for osteosarcopenia.

Zebrafish as a Model for Lipidomics and Similar Investigations.

Zebrafish (Danio rerio) has emerged as a pivotal model organism in vertebrate development research over several decades. Beyond its contributions to developmental biology, zebrafish have increasingly played a crucial role in the field of lipidomics. Lipidomics, a comprehensive analysis of lipids within biological systems, offers profound insights into lipid metabolism and signaling pathways. This chapter explores the zebrafish's unique attributes that make it an ideal candidate for lipidomics studies. With a genome sharing numerous genetic similarities with humans, zebrafish serve as a powerful model for dissecting lipid metabolism and unraveling the complexities of lipid mediator-related diseases. In this chapter, we delve into specific protocols tailored for utilizing zebrafish in lipidomics research and similar investigations. Through a comprehensive exploration of zebrafish as a model organism, this chapter aims to provide researchers with valuable insights and methodologies for advancing lipidomics studies using zebrafish.

The Interplay of Lipid Signaling in Musculoskeletal Cross Talk: Implications for Health and Disease.

The intricate interplay between the muscle and bone tissues is a fundamental aspect of musculoskeletal physiology. Over the past decades, emerging research has highlighted the pivotal role of lipid signaling in mediating communication between these tissues. This chapter delves into the multifaceted mechanisms through which lipids, particularly phospholipids, sphingolipids, and eicosanoids, participate in orchestrating cellular responses and metabolic pathways in both muscle and bone. Additionally, we examine the clinical implications of disrupted lipid signaling in musculoskeletal disorders, offering insights into potential therapeutic avenues. This chapter aims to shed light on the complex lipid-driven interactions between the muscle and bone tissues, paving the way for a deeper understanding of musculoskeletal health and disease.

Differential responses to aging amongst the transcriptome and proteome of mesenchymal progenitor populations.

The biological aging of stem cells (exhaustion) is proposed to contribute to the development of a variety of age-related conditions. Despite this, little is understood about the specific mechanisms which drive this process. In this study, we assess the transcriptomic and proteomic changes in three different populations of mesenchymal progenitor cells from older (50-70 years) and younger (20-40 years) individuals to uncover potential mechanisms driving stem cell exhaustion in mesenchymal tissues. To do this, we harvested primary bone marrow mesenchymal stem and progenitor cells (MPCs), circulating osteoprogenitors (COP), and adipose-derived stem cells (ADSCs) from younger and older donors, with an equal number of samples from males and females. These samples underwent RNA sequencing and label-free proteomic analysis, comparing the younger samples to the older ones. There was a distinct transcriptomic phenotype in the analysis of pooled older stem cells, suggestive of suppressed proliferation and differentiation; however, these changes were not reflected in the proteome of the cells. Analyzed independently, older MPCs had a distinct phenotype in both the transcriptome and proteome consistent with altered differentiation and proliferation with a pro-inflammatory immune shift in older adults. COP cells showed a transcriptomic shift to pro-inflammatory signaling but no consistent proteomic phenotype. Similarly, ADSCs displayed transcriptomic shifts in physiologies associated with cell migration, adherence, and immune activation but no proteomic change with age. These results show that there are underlying transcriptomic changes with stem cell aging that may contribute to a decline in tissue regeneration. However, the proteome of the cells was inconsistently regulated.

Osteosarcopenia increases the risk of mortality: a systematic review and meta-analysis of prospective observational studies.

BACKGROUND & AIMS: Osteosarcopenia is a recently recognized geriatric syndrome. The association between osteosarcopenia and mortality risk is still largely underexplored. In this systematic review with meta-analysis of prospective cohort studies, we aimed to explore whether osteosarcopenia could be associated with a higher mortality risk. METHODS: Several databases were searched from the inception to 16th February 2024 for prospective cohort studies dealing with osteosarcopenia and mortality. We calculated the mortality risk in osteosarcopenia vs. controls using the most adjusted estimate available and summarized the data as risk ratios (RRs) with their 95% confidence intervals (CIs). A random-effect model was considered for all analyses. RESULTS: Among 231 studies initially considered, nine articles were included after exclusions for a total of 14,429 participants (mean age: 70 years; 64.5% females). The weighted prevalence of osteosarcopenia was 12.72%. Over a mean follow-up of 6.6 years and after adjusting for a mean of four covariates, osteosarcopenia was associated with approximately 53% increased risk of mortality (RR: 1.53; 95% CI: 1.28-1.78). After accounting for publication bias, the re-calculated RR was 1.48 (95%CI: 1.23-1.72). The quality of the studies was generally good, as determined by the Newcastle Ottawa Scale. CONCLUSIONS: Osteosarcopenia was significantly linked with an increased risk of mortality in older people, indicating the need to consider the presence of osteoporosis in patients with sarcopenia, and vice versa, since the combination of these two conditions typical of older people may lead to further complications, such as mortality.

Linking sarcopenia, brain structure and cognitive performance: a large-scale UK Biobank study.

Sarcopenia refers to age-related loss of muscle mass and function and is related to impaired somatic and brain health, including cognitive decline and Alzheimer's disease. However, the relationships between sarcopenia, brain structure and cognition are poorly understood. Here, we investigate the associations between sarcopenic traits, brain structure and cognitive performance. We included 33 709 UK Biobank participants (54.2% female; age range 44-82 years) with structural and diffusion magnetic resonance imaging, thigh muscle fat infiltration (n = 30 561) from whole-body magnetic resonance imaging (muscle quality indicator) and general cognitive performance as indicated by the first principal component of a principal component analysis across multiple cognitive tests (n = 22 530). Of these, 1703 participants qualified for probable sarcopenia based on low handgrip strength, and we assigned the remaining 32 006 participants to the non-sarcopenia group. We used multiple linear regression to test how sarcopenic traits (probable sarcopenia versus non-sarcopenia and percentage of thigh muscle fat infiltration) relate to cognitive performance and brain structure (cortical thickness and area, white matter fractional anisotropy and deep and lower brain volumes). Next, we used structural equation modelling to test whether brain structure mediated the association between sarcopenic and cognitive traits. We adjusted all statistical analyses for confounders. We show that sarcopenic traits (probable sarcopenia versus non-sarcopenia and muscle fat infiltration) are significantly associated with lower cognitive performance and various brain magnetic resonance imaging measures. In probable sarcopenia, for the included brain regions, we observed widespread significant lower white matter fractional anisotropy (77.1% of tracts), predominantly lower regional brain volumes (61.3% of volumes) and thinner cortical thickness (37.9% of parcellations), with |r| effect sizes in (0.02, 0.06) and P-values in (0.0002, 4.2e-29). In contrast, we observed significant associations between higher muscle fat infiltration and widespread thinner cortical thickness (76.5% of parcellations), lower white matter fractional anisotropy (62.5% of tracts) and predominantly lower brain volumes (35.5% of volumes), with |r| effect sizes in (0.02, 0.07) and P-values in (0.0002, 1.9e-31). The regions showing the most significant effect sizes across the cortex, white matter and volumes were of the sensorimotor system. Structural equation modelling analysis revealed that sensorimotor brain regions mediate the link between sarcopenic and cognitive traits [probable sarcopenia: P-values in (0.0001, 1.0e-11); muscle fat infiltration: P-values in (7.7e-05, 1.7e-12)]. Our findings show significant associations between sarcopenic traits, brain structure and cognitive performance in a middle-aged and older adult population. Mediation analyses suggest that regional brain structure mediates the association between sarcopenic and cognitive traits, with potential implications for dementia development and prevention.

The Conceptual Definition of Sarcopenia: Delphi Consensus from the Global Leadership Initiative in Sarcopenia (GLIS).

IMPORTANCE: Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists. OBJECTIVE: The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia. DESIGN: The GLIS steering committee was formed in 2019-21 with representatives from all relevant scientific societies worldwide. During this time, the steering committee developed a set of statements on the topic and invited members from these societies to participate in a two-phase International Delphi Study. Between 2022 and 2023, participants ranked their agreement with a set of statements using an online survey tool (SurveyMonkey). Statements were categorised based on predefined thresholds: strong agreement (>80%), moderate agreement (70-80%) and low agreement (<70%). Statements with strong agreement were accepted, statements with low agreement were rejected and those with moderate agreement were reintroduced until consensus was reached. RESULTS: 107 participants (mean age: 54 ± 12 years [1 missing age], 64% men) from 29 countries across 7 continents/regions completed the Delphi survey. Twenty statements were found to have a strong agreement. These included; 6 statements on 'general aspects of sarcopenia' (strongest agreement: the prevalence of sarcopenia increases with age (98.3%)), 3 statements on 'components of sarcopenia' (muscle mass (89.4%), muscle strength (93.1%) and muscle-specific strength (80.8%) should all be a part of the conceptual definition of sarcopenia)) and 11 statements on 'outcomes of sarcopenia' (strongest agreement: sarcopenia increases the risk of impaired physical performance (97.9%)). A key finding of the Delphi survey was that muscle mass, muscle strength and muscle-specific strength were all accepted as 'components of sarcopenia', whereas impaired physical performance was accepted as an 'outcome' rather than a 'component' of sarcopenia. CONCLUSION AND RELEVANCE: The GLIS has created the first global conceptual definition of sarcopenia, which will now serve to develop an operational definition for clinical and research settings.

Leukocyte telomere length is associated with MRI-thigh fat-free muscle volume: data from 16 356 UK Biobank adults.

BACKGROUND: Telomere attrition may share common biological mechanisms with bone and muscle loss with aging. Here, we investigated the association between these hallmarks of aging using data from UK Biobank, a large observational study. METHODS: Leukocyte telomere length (LTL as T/S ratio) was measured using a multiplex qPCR assay at baseline (2006-2010). Bone mineral density (whole body and regional; via dual-energy X-ray absorptiometry), trabecular bone score (via lumbar-spine dual-energy X-ray absorptiometry images), fat-free muscle volume (thighs; via magnetic resonance imaging), and muscle fat infiltration (thighs; via magnetic resonance imaging) were measured during the imaging visit (2014-2018). Regression models were used to model LTL against a muscle or bone outcome, unadjusted and adjusted for covariates. RESULTS: A total of 16 356 adults (mean age: 62.8 ± 7.5 years, 50.5% women) were included. In the fully adjusted model, thigh fat-free muscle volume was associated with LTL in the overall sample (adjusted standardized ß (aß) = 0.017, 95% CI 0.009 to 0.026, P < 0.001, per SD increase in LTL), with stronger associations in men (aß = 0.022, 95% CI 0.010 to 0.034, P < 0.001) than in women (aß = 0.013, 95% CI 0.000 to 0.025, P = 0.041) (sex-LTL P = 0.028). The adjusted odds ratio (aOR) for low thigh fat-free muscle volume (body mass index-adjusted, sex-specific bottom 20%) was 0.93 per SD increase in LTL (95% CI 0.89 to 0.96, P < 0.001) in the overall sample, with stronger associations in men (aOR = 0.92, 95% CI 0.87 to 0.99, P = 0.008) than women (aOR = 0.93, 95% CI 0.88 to 0.98, P = 0.009), although the sex difference was not statistically significant in this model (sex-LTL P = 0.37). LTL was not associated with bone mineral density, trabecular bone score, or muscle fat infiltration in the overall or subgroup analyses (P > 0.05). CONCLUSIONS: LTL was consistently associated with thigh fat-free muscle volume in men and women. Future research should investigate moderating effects of lifestyle factors (e.g., physical activity, nutrition, or chronic diseases) in the association between LTL and muscle volume.

Navigating the Landscape of Translational Geroscience in Canada: A Comprehensive Evaluation of Current Progress and Future Directions.

The inaugural Canadian Conferences on Translational Geroscience were held as 2 complementary sessions in October and November 2023. The conferences explored the profound interplay between the biology of aging, social determinants of health, the potential societal impact of geroscience, and the maintenance of health in aging individuals. Although topics such as cellular senescence, molecular and genetic determinants of aging, and prevention of chronic disease were addressed, the conferences went on to emphasize practical applications for enhancing older people's quality of life. This article summarizes the proceeding and underscores the synergy between clinical and fundamental studies. Future directions highlight national and global collaborations and the crucial integration of early-career investigators. This work charts a course for a national framework for continued innovation and advancement in translational geroscience in Canada.

Expanding access to fracture liaison services in Australia for people with minimal trauma fractures: a system dynamics modelling study.

OBJECTIVES: To project how many minimal trauma fractures could be averted in Australia by expanding the number and changing the operational characteristics of fracture liaison services (FLS). STUDY DESIGN: System dynamics modelling. SETTING, PARTICIPANTS: People aged 50 years or more who present to hospitals with minimal trauma fractures, Australia, 2020-31. MAIN OUTCOME MEASURES: Numbers of all minimal trauma fractures and of hip fractures averted by increasing the FLS number (from 29 to 58 or 100), patient screening rate (from 30% to 60%), and capacity for accepting new patients (from 40 to 80 per service per month), and reducing the proportion of eligible patients who do not attend FLS (from 30% to 15%); cost per fracture averted. RESULTS: Our model projected a total of 2 441 320 minimal trauma fractures (258 680 hip fractures; 2 182 640 non-hip fractures) in people aged 50 years or older during 2020-31, including 1 211 646 second or later fractures. Increasing the FLS number to 100 averted a projected 5405 fractures (0.22%; $39 510 per fracture averted); doubling FLS capacity averted a projected 3674 fractures (0.15%; $35 835 per fracture averted). Our model projected that neither doubling the screening rate nor reducing by half the proportion of eligible patients who did not attend FLS alone would reduce the number of fractures. Increasing the FLS number to 100, the screening rate to 60%, and capacity to 80 new patients per service per month would together avert a projected 13 672 fractures (0.56%) at a cost of $42 828 per fracture averted. CONCLUSION: Our modelling indicates that increasing the number of hospital-based FLS and changing key operational characteristics would achieve only moderate reductions in the number of minimal trauma fractures among people aged 50 years or more, and the cost would be relatively high. Alternatives to specialist-led, hospital-based FLS should be explored.

Nutrient Intake and Its Association with Appendicular Total Lean Mass and Muscle Function and Strength in Older Adults: A Population-Based Study.

Treatment options for sarcopenia are currently limited, and primarily rely on two main therapeutic approaches: resistance-based physical activity and dietary interventions. However, details about specific nutrients in the diet or supplementation are unclear. We aim to investigate the relationship between nutrient intake and lean mass, function, and strength. Data were derived from the Gothenburg H70 birth cohort study in Sweden, including 719,70-year-olds born in 1944 (54.1% females). For independent variables, the diet history method (face-to-face interviews) was used to estimate habitual food intake during the preceding three months. Dependent variables were gait speed (muscle performance), hand grip strength (muscle strength), and the appendicular lean soft tissue index (ALSTI). Linear regression analyses were performed to analyze the relationship between the dependent variables and each of the covariates. Several nutrients were positively associated with ALSTI, such as polyunsaturated fatty acids (DHA, EPA), selenium, zinc, riboflavin, niacin equivalent, vitamin B12, vitamin D, iron, and protein. After correction for multiple comparisons, there were no remaining correlations with handgrip and gait speed. Findings of positive correlations for some nutrients with lean mass suggest a role for these nutrients in maintaining muscle volume. These results can be used to inform clinical trials to expand the preventive strategies and treatment options for individuals at risk of muscle loss and sarcopenia.

Temporal Muscle Thickness: A Practical Approximation for Assessing Muscle Mass in Older Adults.

OBJECTIVE: Ongoing research has evidenced the importance of muscle measurement in predicting adverse outcomes. Measurement of other muscles is promising in current research. This study aimed to determine the correlation between temporal muscle thickness (TMT) and appendicular lean soft tissue (ALSTI) in older adults. DESIGN: Cross-sectional study. SETTINGS AND PARTICIPANTS: Single cohort gathered in Gothenburg, Sweden, consisting of individuals born in 1944 (n = 1203). METHODS: We studied 657 magnetic resonance images to measure TMT. Comparisons of TMT with dual-energy X-ray absorptiometry ALSTI (kg/m2) as a reference standard were performed. Finally, TMT associations with cognition evaluated using the Mini-Mental State Examination (MMSE), gait speed, and handgrip strength were explored with linear regressions. RESULTS: The correlation between TMT and ALSTI was weak yet significant (r = 0.277, P < .001). TMT exhibited significant associations with MMSE (estimate = 0.168, P = .002), gait speed (estimate = 1.795, P < .001), and ALSTI (estimate = 0.508, P < .001). These associations varied when analyzed by sex. In women, TMT was significantly associated with gait speed (estimate = 1.857, P = .005) and MMSE (estimate = 0.223, P = .003). In men, TMT scores were significantly correlated with ALSTI scores (estimate = 0.571, P < .001). CONCLUSION AND IMPLICATIONS: Repurposing head images can be an accessible alternative to detect muscle mass and ultimately detect sarcopenia. These studies have the potential to trigger interventions or further evaluation to improve the muscle and overall health of individuals. However, additional research is warranted before translating these findings into clinical practice.

Fat as a Friend or Foe of the Bone.

PURPOSE OF REVIEW: The objective of this review is to summarize the literature on the prevalence and diagnosis of obesity and its metabolic profile, including bone metabolism, focusing on the main inflammatory and turnover bone mediators that better characterize metabolically healthy obesity phenotype, and to summarize the therapeutic interventions for obesity with their effects on bone health. RECENT FINDINGS: Osteoporosis and fracture risk not only increase with age and menopause but also with metabolic diseases, such as diabetes mellitus. Thus, patients with high BMI may have a higher bone fragility and fracture risk. However, some obese individuals with healthy metabolic profiles seem to be less at risk of bone fracture. Obesity has become an alarming disease with growing prevalence and multiple metabolic comorbidities, resulting in a significant burden on healthcare and increased mortality. The imbalance between increased food ingestion and decreased energy expenditure leads to pathological adipose tissue distribution and function, with increased secretion of proinflammatory markers and harmful consequences for body tissues, including bone tissue. However, some obese individuals seem to have a healthy metabolic profile and may not develop cardiometabolic disease during their lives. This healthy metabolic profile also benefits bone turnover and is associated with lower fracture risk.

Exercise as a Therapeutic Tool in Age-Related Frailty and Cardiovascular Disease: Challenges and Strategies.

Understanding the link between heart disease and frailty in older adults is crucial. Although medical progress has extended life, it has not fully addressed the decline in function and quality of life in frail older people. Frailty is a state of vulnerability to health stressors that needs comprehensive solutions. Its assessment within health care, especially in cardiology, is important owing to its association with worse clinical outcomes. Recent evidence and guidelines suggest that the prescription of a comprehensive exercise regimen, tailored to progressively include strength, balance, mobility, and endurance training improves adherence, functionality, and health-related quality of life, in both acute and chronic cardiovascular diseases. In addition, exercise is a vital tool that improves function, targets frailty, and holistically affects the body's systems. Still, many frail people do not exercise enough, and when they do, they usually do not follow an appropriate plan tailored for better functional outcomes. Overcoming barriers and limitations in exercise enrollment and adherence through strategies such as automated cardiac rehabilitation referral, patient education, and eHealth tools can notably improve clinical outcomes.

Challenges in Delivering Effective Care for Older Persons with Fragility Fractures.

Fragility fractures occur because of low-impact trauma or even spontaneously in individuals with osteoporosis. Caring for older persons with fragility fractures can present several challenges due to the unique needs and vulnerabilities of this population. Older individuals commonly have multiple medical conditions, such as osteoporosis, arthritis, cardiovascular diseases, and diabetes. These comorbidities can complicate fracture management and increase the risk of complications. Fracture repair through surgery may be more complex in older patients due to poor bone quality, decreased tissue elasticity, and higher chances of anesthesia complications. In addition, mobility and functional limitations post-fracture are highly prevalent in this population, affecting their independence and increasing their risk of institutionalization. Addressing these challenges requires a multidisciplinary approach involving orthopedic surgeons, geriatricians, physical and rehabilitation physicians, physiotherapists, occupational therapists, dieticians, social workers, and caregivers. Preventive measures, such as fall prevention strategies and osteoporosis management, can also play a vital role in reducing the incidence of fragility fractures in older persons.

Exploring new balance and gait factors that are associated with osteosarcopenia in patients with a previous fall and/or fracture history.

Osteosarcopenic individuals have poor muscle function and increased bone fragility, which results in a severe detriment to health outcomes. Hence, there is a necessity to discover easily accessible factors associated with osteosarcopenia to develop timely interventions. This study aimed to determine new sensitive balance and/or gait variables that are associated with osteosarcopenia in a population of older people with a history of falls and/or fractures. In a cross-sectional cohort study, 306 men and women aged ≥65 years completed a series of questionnaires, clinical assessments and muscle strength and function tests. Subsequently, participants were separated into osteopenia, osteoporosis and osteosarcopenia, groups for comparison and further analysis. Osteosarcopenia performed worse than osteopenia and osteoporosis in grip strength, gait speed, physical function scores and in multiple gait and balance indices (p<0.001). During posturography testing, there were larger elliptical areas with eyes open (p = 0.003), and eyes closed (p = 0.043) and increased sway velocity on a firm platform (p = 0.007) in the osteosarcopenia group, compared to osteoporosis. Limits of stability and eyes open ellipse area significantly contributed to the multivariable model (p = 0.029 and p = 0.038, respectively), suggesting that these balance parameters, along with grip strength, may be useful in identifying older adults with osteosarcopenia from those with only osteopenia/osteoporosis. Older adults with osteosarcopenia and a history of falls and/or fractures demonstrated inferior strength, function, and gait characteristics. This study identified indices of balance that were sensitive discriminators for osteosarcopenia and could be easily implemented into routine assessment.

Classification of Fracture Risk in Fallers Using Dual-Energy X-Ray Absorptiometry (DXA) Images and Deep Learning-Based Feature Extraction.

Dual-energy X-ray absorptiometry (DXA) scans are one of the most frequently used imaging techniques for calculating bone mineral density, yet calculating fracture risk using DXA image features is rarely performed. The objective of this study was to combine deep neural networks, together with DXA images and patient clinical information, to evaluate fracture risk in a cohort of adults with at least one known fall and age-matched healthy controls. DXA images of the entire body as, well as isolated images of the hip, forearm, and spine (1488 total), were obtained from 478 fallers and 48 non-faller controls. A modeling pipeline was developed for fracture risk prediction using the DXA images and clinical data. First, self-supervised pretraining of feature extractors was performed using a small vision transformer (ViT-S) and a convolutional neural network model (VGG-16 and Resnet-50). After pretraining, the feature extractors were then paired with a multilayer perceptron model, which was used for fracture risk classification. Classification was achieved with an average area under the receiver-operating characteristic curve (AUROC) score of 74.3%. This study demonstrates ViT-S as a promising neural network technique for fracture risk classification using DXA scans. The findings have future application as a fracture risk screening tool for older adults at risk of falls. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Sarcopenic obesity definitions and their associations with physical frailty in older Brazilian adults: data from the SARCOS study

ABSTRACT Objective: To identify the obesity diagnosis with the highest association with physical frailty associated with sarcopenia EWGSOP II (sarcopenic obesity). Subjects and methods: We performed a cross-sectional analysis of 371 community-dwelling older adults. Appendicular skeletal lean mass and total body fat (TBF) were assessed using dual-energy x-ray absorptiometry, and physical frailty was defined using Fried's criteria. The phenotypes were identified according to the presence of sarcopenia by EWGSOP II and obesity, which was diagnosed using two concepts: BMI obesity (BMI ≥ 30 kg/m2) and TBF obesity (percentage of TBF ≥ 35% for women and ≥ 25% for men). Finally, the association of each group with physical frailty was evaluated. Results: The mean age was 78.15 ± 7.22 years. Sarcopenia EWGSOP II was diagnosed in 19.8% (n = 73), body mass index obesity was identified in 21.8% (n = 81), TBF obesity was identified in 67.7% (n = 251), and physical frailty was identified in 38.5% (n = 142). In a regression analysis for frailty, sarcopenic TBF obesity presented an odds ratio of 6.88 (95% confidence interval 2.60-18.24; p < 0.001). Conclusion: In older Brazilian adults, sarcopenic obesity diagnosed by TBF obesity has a robust association with frailty and is independent of body mass index.

Differential responses to aging amongst the transcriptome and proteome of mesenchymal progenitor populations.

The biological aging of mesenchymal stem cells is proposed to contribute to the development of a range of musculoskeletal and systemic diseases associated with older adults, such as osteoporosis, sarcopenia, and frailty. Despite this, little is understood about the specific mechanisms which drive this stem cell exhaustion, with most studies evaluating indirect effects of other aging changes, such as DNA damage, senescence, and inflammaging. In this study, we assess the transcriptomic and proteomic changes in three different populations of mesenchymal progenitor cells from older (50-70 years) and younger (20-40 years) individuals to uncover potential mechanisms driving stem cell exhaustion in mesenchymal tissues. To do this, we harvested primary bone marrow mesenchymal stem and progenitor cells (MPCs), circulating osteoprogenitors (COP), and adipose-derived stem cells (ADSCs) from younger and older donors, with an equal number of samples from males and females. These samples underwent RNA sequencing and label-free proteomic analysis, comparing the younger samples to the older ones. There was a distinct transcriptomic phenotype associated with the pooled older stem cells, indicative of suppressed proliferation and differentiation; however, there was no consistent change in the proteome of the cells. Older MPCs had a distinct phenotype in both the transcriptome and proteome, again consistent with altered differentiation and proliferation, but also a pro-inflammatory immune shift in older adults. COP cells showed a strong transcriptomic shift to pro-inflammatory signaling but no consistent proteomic phenotype. Similarly, ADSCs displayed transcriptomic shift in physiologies associated with cell migration, adherence, and immune activation, but no consistent proteomic change with age. These results show that there are underlying transcriptomic changes with stem cell aging that likely contribute to a decline in tissue regeneration; however, contextual factors such as the microenvironment and general health status also have a strong role in this.