Search

Background: Ageing is accompanied by a progressive loss of skeletal muscle mass and strength, potentially determining the insurgence of sarcopenia. Evidence suggests that motoneuron and neuromuscular junction (NMJ) degeneration contribute to sarcopenia pathogenesis. Seeking for strategies able to slow down sarcopenia insurgence and progression, we investigated whether a 2-year mixed-model training involving aerobic, strength and balance exercises would be effective for improving or preserving motoneuronal health and NMJ stability, together with muscle mass, strength and functionality in an old, sarcopenic population., Methods: Forty-five sarcopenic elderly (34 females; 11 males) with low dual-energy X-ray absorptiometry (DXA) lean mass and Short Physical Performance Battery (SPPB) score <9 were randomly assigned to either a control group [Healthy Aging Lifestyle Education (HALE), n = 21] or an intervention group [MultiComponent Intervention (MCI), n = 24]. MCI trained three times per week for 2 years with a mix of aerobic, strength and balance exercises matched with nutritional advice. Before and after the intervention, ultrasound scans of the vastus lateralis (VL), SPPB and a blood sample were obtained. VL architecture [pennation angle (PA) and fascicle length (Lf)] and cross-sectional area (CSA) were measured. As biomarkers of neuronal health and NMJ stability status, neurofilament light chain (NfL) and C-terminal agrin fragment (CAF) concentrations were measured in serum. Differences in ultrasound parameters, NfL and CAF concentration and physical performance between baseline and follow-up were tested with mixed ANOVA or Wilcoxon test. The relationship between changes in physical performance and NfL or CAF concentration was assessed through correlation analyses., Results: At follow-up, MCI showed preserved VL architecture (PA, Lf) despite a reduced CSA (-8.4%, P < 0.001), accompanied by maintained CAF concentration and ameliorated overall SPPB performance (P = 0.007). Conversely, HALE showed 12.7% decrease in muscle CSA (P < 0.001), together with 5.1% and 5.5% reduction in PA and Lf (P < 0.001 and P = 0.001, respectively), and a 6.2% increase in CAF (P = 0.009) but improved SPPB balance score (P = 0.007). NfL concentration did not change in either group. In the population, negative correlations between changes in CAF concentration and SPPB total score were found (P = 0.047), whereas no correlation between NfL and SPPB variations was observed., Conclusions: The present findings suggest that our 2-year mixed aerobic, strength and balance training seemed effective for preventing the age and sarcopenia-related increases in CAF concentration, preserving NMJ stability as well as muscle structure (PA and Lf) and improving physical performance in sarcopenic older individuals., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Cardiac structure and function change with age. The higher prevalence of left ventricular hypertrophy (LVH) with concentric remodeling is indicative of a typical geometric pattern of aging associated with a higher cardiovascular (CV) risk and diseases. The recent associations found between low left ventricular and skeletal mass in older patients with frailty and sarcopenia have raised great interest in investigating cardiac characteristics and determinants of left ventricular mass (LVM) in this population., Design: Cross-sectional study., Methods: We evaluated 100 sarcopenic and physically frail outpatients, 33 men (M), 67 women (F), aged ≥70 years (mean age 79 ± 5) and enrolled in the Parma site of European multicenter SPRINTT population., Results: All male and female participants showed LVH, assessed as indexed LVM to body surface area (LVM/BSA) (M = 128 ± 39 g/m 2 ; F = 104 ± 26 g/m 2 ), and were more prone to have concentric geometry, as demonstrated by relative wall thickness value (0.41 in both sexes). After backward regression analysis, including covariates such as age, sex, office or ABPM systolic blood pressure (SBP), heart rate, BSA, use of β blockers, ACE-inhibitors, angiotensin receptor blockers, calcium channel blockers, diuretics, physical activity, hemoglobin level, and Mini Mental State examination - the most powerful determinants of LVM were clinical SBP (β = 1.51 ± 0.31, p = 0.0005), BSA (β = 165.9 ± 41.4, p = 0.0001), while less powerful determinants were 24 h, daily and nightly SBP (p = 0.02, p = 0.002, p = 0.004 respectively)., Conclusions: Older sarcopenic and physically frail patients showed LVH with a tendency towards concentric geometry. The main determinant of LVM was SBP, highlighting the key role that hemodynamic condition plays in determining LVH in this population., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Physical frailty and sarcopenia (PF&S) is a prototypical geriatric condition characterized by reduced physical function and low muscle mass. The aim of the present study was to provide an initial selection of biomarkers for PF&S using a novel multivariate analytic strategy. Two-hundred community-dwellers, 100 with PF&S and 100 non-physically frail, non-sarcopenic (nonPF&S) controls aged 70 and older were enrolled as part of the BIOmarkers associated with Sarcopenia and Physical frailty in EldeRly pErsons (BIOSPHERE) study. A panel of 74 serum analytes involved in inflammation, muscle growth and remodeling, neuromuscular junction damage, and amino acid metabolism was assayed. Biomarker selection was accomplished through sequential and orthogonalized covariance selection (SO-CovSel) analysis. Separate SO-CovSel models were constructed for the whole study population and for the two genders. The model with the best prediction ability obtained with the smallest number of variables was built using seven biomolecules. This model allowed correct classification of 80.6 ± 5.3% PF&S participants and 79.9 ± 5.1% nonPF&S controls. The PF&S biomarker profile was characterized by higher serum levels of asparagine, aspartic acid, and citrulline. Higher serum concentrations of platelet-derived growth factor BB, heat shock protein 72 (Hsp72), myeloperoxidase, and α-aminobutyric acid defined the profile of nonPF&S participants. Gender-specific SO-CovSel models identified a "core" biomarker profile of PF&S, characterized by higher serum levels of aspartic acid and Hsp72 and lower concentrations of macrophage inflammatory protein 1β, with peculiar signatures in men and women.SO-CovSel analysis allowed identifying a set of potential biomarkers for PF&S. The adoption of such an innovative multivariate approach could help address the complex pathophysiology of PF&S, translate biomarker discovery from bench to bedside, and unveil novel targets for interventions.

Physical frailty and sarcopenia (PF&S) recapitulates all the hallmarks of aging and has become a focus in geroscience. Factors spanning muscle-specific processes (e.g., mitochondrial dysfunction in skeletal myocytes) to systemic changes (e.g., inflammation and amino acid dysmetabolism) have been pinpointed as possible contributors to PF&S pathophysiology. However, the search for PF&S biomarkers allowing the early identification and tracking of the condition over time is ongoing. This is mainly due to the phenotypic heterogeneity of PF&S, its unclear pathophysiology, and the frequent superimposition of other age-related conditions. Hence, presently, the identification of PF&S relies upon clinical, functional, and imaging parameters. The adoption of multi-marker approaches (combined with multivariate modeling) has shown great potential for addressing the complexity of PF&S pathophysiology and identifying candidate biological markers. Well-designed longitudinal studies are necessary for the incorporation of reliable biomarkers into clinical practice and for unveiling novel targets that are amenable to interventions.

Mitochondrial dysfunction and systemic inflammation are major factors in the development of sarcopenia, but the molecular determinants linking the two mechanisms are only partially understood. The study of extracellular vesicle (EV) trafficking may provide insights into this relationship. Circulating small EVs (sEVs) from serum of 11 older adults with physical frailty and sarcopenia (PF&S) and 10 controls were purified and characterized. Protein levels of three tetraspanins (CD9, CD63, and CD81) and selected mitochondrial markers, including adenosine triphosphate 5A (ATP5A), mitochondrial cytochrome C oxidase subunit I (MTCOI), nicotinamide adenine dinucleotide reduced form (NADH):ubiquinone oxidoreductase subunit B8 (NDUFB8), NADH:ubiquinone oxidoreductase subunit S3 (NDUFS3), succinate dehydrogenase complex iron sulfur subunit B (SDHB), and ubiquinol-cytochrome C reductase core protein 2 (UQCRC2) were quantified by Western immunoblotting. Participants with PF&S showed higher levels of circulating sEVs relative to controls. Protein levels of CD9 and CD63 were lower in the sEV fraction of PF&S older adults, while CD81 was unvaried between groups. In addition, circulating sEVs from PF&S participants had lower amounts of ATP5A, NDUFS3, and SDHB. No signal was detected for MTCOI, NDUFB8, or UQCRC2 in either participant group. Our findings indicate that, in spite of increased sEV secretion, lower amounts of mitochondrial components are discarded through EV in older adults with PF&S. In-depth analysis of EV trafficking might open new venues for biomarker discovery and treatment development for PF&S.

Physical frailty and sarcopenia (PF&S) share multisystem derangements, including variations in circulating amino acids and chronic low-grade inflammation. Gut microbiota balances inflammatory responses in several conditions and according to nutritional status. Therefore, an altered gut-muscle crosstalk has been hypothesized in PF&S. We analyzed the gut microbial taxa, systemic inflammation, and metabolic characteristics of older adults with and without PF&S. An innovative multi-marker analytical approach was applied to explore the classification performance of potential biomarkers for PF&S. Thirty-five community dwellers aged 70+, 18 with PF&S, and 17 nonPF&S controls were enrolled. Sequential and Orthogonalized Covariance Selection (SO-CovSel), a multi-platform regression method developed to handle highly correlated variables, was applied. The SO-CovSel model with the best prediction ability using the smallest number of variables was built using seven mediators. The model correctly classified 91.7% participants with PF&S and 87.5% nonPF&S controls. Compared with the latter group, PF&S participants showed higher serum concentrations of aspartic acid, lower circulating levels of concentrations of threonine and macrophage inflammatory protein 1α, increased abundance of Oscillospira and Ruminococcus microbial taxa, and decreased abundance of Barnesiellaceae and Christensenellaceae. Future investigations are warranted to determine whether these biomediators are involved in PF&S pathophysiology and may, therefore, provide new targets for interventions.

Background: The construct of physical frailty and sarcopenia (PF&S) identifies an age-related pre-disability condition defined by reduced physical performance and low muscle mass. Whether PF&S is characterized by perturbations of the cytokine network is presently unclear. Furthermore, the existence of gender-specific inflammatory profiles of PF&S is unknown. This study was designed to explore the association between a large panel of inflammatory biomolecules and PF&S in older adults through a multivariate statistical approach. Gender-specific inflammatory patterns were also explored., Methods: One-hundred community-dwellers aged 70 years and older with PF&S and 100 non-sarcopenic, non-frail controls (nonPF&S) were enrolled. A panel of 30 circulating inflammatory biomarkers was assayed. Partial least squares discriminant analysis (PLS-DA) was employed to explore the relationship between inflammatory molecules and PF&S. Separate PLS-DA models were built for the whole sample and the two genders. Double cross-validation procedures were used to validate the predictive ability of PLS-DA models., Results: The optimal complexity of the PLS-DA model built on the whole sample was found to be four latent variables. The proportion of correct classification was 75.6 ± 1.3% (82.3 ± 1.6% for enrollees with PF&S and 68.7 ± 2.5% for nonPF&S controls). The inflammatory profile of people with PF&S was defined by higher levels of P-selectin, C-reactive protein (CRP), and interferon γ-induced protein 10. NonPF&S participants were characterized by higher levels of myeloperoxidase (MPO), interleukin (IL) 8, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1-α, platelet-derived growth factor (PDGF) BB. Gender-specific PLS-DA allowed identifying a "core" inflammatory signature of PF&S, composed by higher levels of CRP, and lower concentrations of MPO, IL8, MCP-1, and PDGF-BB, with peculiar patterns of relationships for men and women., Conclusions: A core inflammatory profile was identified in people with PF&S with a gender-specific signature. The dissection of the PF&S "cytokinome" will provide novel insights into the role played by inflammation in the disabling cascade and allow designing personalized treatment strategies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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).

Background: People with Down syndrome (DS) experience premature aging. Whether this accelerated aging also involves early declines in muscle mass, strength and physical performance is presently unclear. The present study investigated the prevalence of sarcopenia parameters in adults with DS. In addition, the relationship between well-established muscle mass indexes and a set of body composition, functional, biological, and clinical parameters was explored., Methods: One hundred-five adults with DS participated in the study. Demographic, clinical, anthropometric, and functional parameters were assessed. Lean body mass (LBM) was estimated using bioelectrical impedance analysis. Bone mineral density (BMD) of the hip and the spine was measured through dual X-ray absorptiometry. For the analysis, participants were categorized into two subgroups (i.e., low and high) for each LBM-related measurement (i.e., crude LBM, LBM to body mass index ratio, and skeletal muscle index) according to their median values., Results: The mean age of participants was 38.4 ± 12.1 years, with 43 men (41%). Muscle mass, handgrip strength, and gait speed were lower than established cutoffs for sarcopenia. All muscle mass indexes were negatively correlated with age. However, only crude LBM and the skeletal muscle index were correlated with a set of anthropometric parameters and BMD., Conclusion: Findings from this exploratory study indicate that adults with DS show muscle mass indexes and physical performance levels similar to or lower than older adults with sarcopenia. The assessment of muscle mass and functional status should therefore be included in the routine evaluation of this population starting at young age., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Mitochondrial dysfunction is a hallmark of aging and hence is a candidate target for intervention. Sarcopenia of aging is a prevalent condition and is associated with numerous negative health outcomes. Alterations in mitochondrial homeostasis have been reported in sarcopenic muscle. Area covered: We discuss the evidence that points to mitochondrial dysfunction having a causative role in sarcopenia and the mechanisms involved in the accumulation of damaged mitochondria in the aged muscle. We also discuss the effects of physical exercise on mitochondrial quality control and muscle health in advanced age. Expert opinion: In the aged muscle, the mitochondrial quality control axis is altered at several levels, including proteostasis, biogenesis, dynamics, and autophagy. Mitochondrial dysfunction arising from impaired quality control is thought to play a major role in the pathogenesis of sarcopenia. Physical exercise is the most effective strategy for the management of sarcopenia. Improvements in mitochondrial health and plasticity may mediate several beneficial effects of exercise in muscle. A greater understanding of the molecular changes that occur in the aged muscle following exercise and how they impact mitochondrial homeostasis is necessary for the exploration of potential targets that are amenable for interventions.

Physical frailty and sarcopenia (PF&S) are hallmarks of aging that share a common pathogenic background. Perturbations in protein/amino acid metabolism may play a role in the development of PF&S. In this initial report, 68 community-dwellers aged 70 years and older, 38 with PF&S and 30 non-sarcopenic, non-frail controls (nonPF&S), were enrolled as part as the "BIOmarkers associated with Sarcopenia and Physical frailty in EldeRly pErsons" (BIOSPHERE) study. A panel of 37 serum amino acids and derivatives was assayed by UPLC-MS. Partial Least Squares⁻Discriminant Analysis (PLS-DA) was used to characterize the amino acid profile of PF&S. The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classification was 76.6 ± 3.9% (75.1 ± 4.6% for enrollees with PF&S; 78.5 ± 6.0% for nonPF&S). Older adults with PF&S were characterized by higher levels of asparagine, aspartic acid, citrulline, ethanolamine, glutamic acid, sarcosine, and taurine. The profile of nonPF&S participants was defined by higher concentrations of α-aminobutyric acid and methionine. Distinct profiles of circulating amino acids and derivatives characterize older people with PF&S. The dissection of these patterns may provide novel insights into the role played by protein/amino acid perturbations in the disabling cascade and possible new targets for interventions.

Background: The ongoing "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies (SPRINTT)" randomized controlled trial (RCT) is testing the efficacy of a multicomponent intervention in the prevention of mobility disability in older adults with physical frailty & sarcopenia (PF&S). Here, we describe the procedures followed for PF&S case finding and screening of candidate participants for the SPRINTT RCT. We also illustrate the main demographic and clinical characteristics of eligible screenees., Methods: The identification of PF&S was based on the co-occurrence of three defining elements: (1) reduced physical performance (defined as a score on the Short Physical Performance Battery between 3 and 9); (2) low muscle mass according to the criteria released by the Foundation for the National Institutes of Health; and (3) absence of mobility disability (defined as ability to complete the 400-m walk test in 15 min). SPRINTT was advertised through a variety of means. Site-specific case finding strategies were developed to accommodate the variability across centers in catchment area characteristics and access to the target population. A quick "participant profiling" questionnaire was devised to facilitate PF&S case finding., Results: During approximately 22 months, 12,358 prescreening interviews were completed in 17 SPRINTT sites resulting in 6710 clinic screening visits. Eventually, 1566 candidates were found to be eligible for participating in the SPRINTT RCT. Eligible screenees showed substantial physical function impairment and comorbidity burden. In most centers, project advertisement through mass media was the most rewarding case finding strategy., Conclusion: PF&S case finding in the community is a challenging, but feasible task. Although largely autonomous in daily life activities, older adults with PF&S suffer from significant functional impairment and comorbidity. This subset of the older population is therefore at high risk for disability and other negative health-related events. Key strategies to consider for successfully intercepting at-risk older adults should focus on mass communication methods., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Sarcopenia, the progressive and generalised loss of muscle mass and strength/function, is a major health issue in older adults given its high prevalence and burdensome clinical implications. Over the years, this condition has been endorsed as a marker for discriminating biological from chronological age. However, the absence of a unified operational definition has hampered its full appreciation by healthcare providers, researchers and policy-makers. In addition to this unsolved debate, the complexity of musculoskeletal ageing represents a major challenge to the identification of clinically meaningful biomarkers. Here, we illustrate the advantages of biomarker discovery procedures in muscle ageing based on multivariate methodologies as an alternative approach to traditional single-marker strategies. The rationale, design and methods of the "BIOmarkers associated with Sarcopenia and PHysical frailty in EldeRly pErsons" (BIOSPHERE) study are described as an application of a multi-marker strategy for the development of biomarkers for the newly operationalised Physical Frailty & Sarcopenia condition., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Mitochondrial structural and functional integrity is maintained through the coordination of several processes (e.g., biogenesis, dynamics, mitophagy), collectively referred to as mitochondrial quality control (MQC). Dysfunctional MQC and inflammation are hallmarks of aging and are involved in the pathogenesis of muscle wasting disorders, including sarcopenia and cachexia. One of the consequences of failing MQC is the release of mitochondria-derived damage-associated molecular patterns (DAMPs). By virtue of their bacterial ancestry, these molecules can trigger an inflammatory response by interacting with receptors similar to those involved in pathogen-associated responses. Mitochondria-derived DAMPs, especially cell-free mitochondrial DNA, have recently been associated with conditions characterized by chronic inflammation, such as aging and degenerative diseases. Yet, their actual implication in the aging process and muscle wasting disorders is at an early stage of investigation. Here, we review the contribution of mitochondria-derived DAMPs to age-related systemic inflammation. We also provide arguments in support of the exploitation of such signaling pathways for the management of muscle wasting conditions.

Sarcopenia and frailty are associated with several important health-related adverse events, including disability, loss of independence, institutionalization and mortality. Sarcopenia can be considered a biological substrate of frailty, and the prevalence of both these conditions progressively increases with age. Telomeres are nucleoprotein structures located at the end of linear chromosomes and implicated in cellular ageing, shorten with age, and are associated with various age-related diseases. In addition, telomere length (TL) is widely considered a molecular/cellular hallmark of the ageing process. This narrative review summarizes the knowledge about telomeres and analyzes for the first time a possible association of TL with sarcopenia and frailty. The overview provided by the present review suggests that leukocyte TL as single measurement, calculated by quantitative real-time polymerase chain reaction (qRT-PCR), cannot be considered a meaningful biological marker for complex, multidimensional age-related conditions, such as sarcopenia and frailty. Panels of biomarkers, including TL, may provide more accurate assessment and prediction of outcomes in these geriatric syndromes in elderly people.

Objectives: In Parkinson disease (PD), sarcopenia may represent the common downstream pathway that from motor and nonmotor symptoms leads to the progressive loss of resilience, frailty, and disability. Here we (1) assessed the prevalence of sarcopenia in older adults with PD using 3 different criteria, testing their agreement, and (2) evaluated the association between PD severity and sarcopenia., Design: Cross-sectional, observation study., Setting: Geriatric day hospital., Participants: Older adults with idiopathic PD., Measurements: Body composition was evaluated through dual energy x-ray absorptiometry. Handgrip strength and walking speed were measured. Sarcopenia was operationalized according to the Foundation for the National Institutes of Health, the European Working Group on Sarcopenia in Older Persons, and the International Working Group. Cohen k statistics was used to test the agreement among criteria., Results: Among the 210 participants (mean age 73 years; 38% women), the prevalence of sarcopenia was 28.5%-40.7% in men and 17.5%-32.5% in women. The prevalence of severe sarcopenia was 16.8%-20.0% in men and 11.3%-18.8% in women. The agreement among criteria was poor. The highest agreement was obtained between the European Working Group on Sarcopenia in Older Persons (severe sarcopenia) and International Working Group criteria (k = 0.52 in men; k = 0.65 in women; P < .01 for both). Finally, severe sarcopenia was associated with PD severity (odds ratio 2.30; 95% confidence interval 1.15-4.58)., Conclusions: Sarcopenia is common in PD, with severe sarcopenia being diagnosed in 1 in every 5 patients with PD. We found a significant disagreement among the 3 criteria evaluated, in detecting sarcopenia more than in ruling it out. Finally, sarcopenia is associated with PD severity. Considering its massive prevalence, further studies should address the prognosis of sarcopenia in PD., (Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Sarcopenia is a well-known geriatric syndrome that has been endorsed over the years as a biomarker allowing for the discrimination, at a clinical level, of biological from chronological age. Multiple candidate mechanisms have been linked to muscle degeneration during sarcopenia. Among them, there is wide consensus on the central role played by the loss of mitochondrial integrity in myocytes, secondary to dysfunctional quality control mechanisms. Indeed, mitochondria establish direct or indirect contacts with other cellular components (e.g. endoplasmic reticulum, peroxisomes, lysosomes/vacuoles) as well as the extracellular environment through the release of several biomolecules. The functional implications of these interactions in the context of muscle physiology and sarcopenia are not yet fully appreciated and represent a promising area of investigation. Here, we present an overview of recent findings concerning the interrelation between mitochondrial quality control processes, inflammation and the metabolic regulation of muscle mass in the pathogenesis of sarcopenia highlighting those pathways that may be exploited for developing preventive and therapeutic interventions against muscle aging.

Advanced age is characterized by several changes, one of which is the impairment of the homeostasis of intestinal microbiota. These alterations critically influence host health and have been associated with morbidity and mortality in older adults. "Inflammaging," an age-related chronic inflammatory process, is a common trait of several conditions, including sarcopenia. Interestingly, imbalanced intestinal microbial community has been suggested to contribute to inflammaging. Changes in gut microbiota accompanying sarcopenia may be attenuated by supplementation with pre- and probiotics. Although muscle aging has been increasingly recognized as a biomarker of aging, the pathophysiology of sarcopenia is to date only partially appreciated. Due to its development in the context of the age-related inflammatory milieu, several studies favor the hypothesis of a tight connection between sarcopenia and inflammaging. However, conclusive evidence describing the signaling pathways involved has not yet been produced. Here, we review the current knowledge of the changes in intestinal microbiota that occur in advanced age with a special emphasis on findings supporting the idea of a modulation of muscle physiology through alterations in gut microbial composition and activity.

Sarcopenia, the progressive and generalized loss of muscle mass and strength/function, is a major health issue in older adults, given its high prevalence and burdensome clinical ramifications. The absence of a unified operational definition for sarcopenia has hampered its full appreciation by healthcare providers, researchers and policy-makers. At the same time, this unresolved debate and the complexity of musculoskeletal aging pose major challenges to the identification of clinically meaningful biomarkers. This review summarizes the current knowledge on biological markers for sarcopenia, including a critical appraisal of traditional procedures for biomarker development in the field of muscle aging. As an alternative approach, we illustrate the potential advantages of biomarker discovery procedures based on multivariate methodologies. Relevant examples of multidimensional biomarker modeling are provided with an emphasis on its clinical and research application., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Mitochondrial quality control (MQC) is crucial for maintaining mitochondrial fitness. We investigated MQC signaling in muscle of old hip-fractured patients., Methods: Twenty-three patients, enrolled in the Sarcopenia in HIp FracTure (SHIFT) study, were categorized into old (OL; n=8) and very old groups (VOL; n=15) using 85years as the cut-off. The expression of a set of MQC signaling proteins was assayed in vastus lateralis muscle biopsies., Results: The content of lysosome-associated membrane protein 2, microtubule-associated protein 1 light chain 3B, optic atrophy protein 1, fission protein 1 (Fis1), peroxisome proliferator-activated receptor-γ coactivator-1α, and forkhead box O3 was unvaried between groups. Conversely, the protein expression of mitofusin 2 (Mfn2) as well as the fusion index (Mfn2/Fis1) was increased in VOL patients., Conclusions: Muscle mitochondrial dynamics appear to be shifted toward fusion in very advanced age. Whether this phenomenon represents an adaptation to cope with age-dependent mitochondrial dysfunction warrants further investigation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Sarcopenia encompasses the loss of muscle mass and strength/function during aging. Several methods are available for the estimation of muscle or lean body mass. Popular assessment tools include body imaging techniques (e.g., magnetic resonance imaging, computed tomography, dual X-ray absorptiometry, ultrasonography), bioelectric impedance analysis, anthropometric parameters (e.g., calf circumference, mid-arm muscle circumference), and biochemical markers (total or partial body potassium, serum and urinary creatinine, deuterated creatine dilution method). The heterogeneity of the populations to be evaluated as well as the setting in which sarcopenia is investigated impacts the definition of "gold standard" assessment techniques. The aim of this article is to critically review available methods for muscle mass estimation, highlighting strengths and weaknesses of each of them as well as their proposed field of application.

In the present article, the rationale that guided the operationalization of the theoretical concept of physical frailty and sarcopenia (PF&S), the condition of interest for the "Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies" (SPRINTT) trial, is presented. In particular, the decisions lead to the choice of the adopted instruments, and the reasons for setting the relevant thresholds are explained. In SPRINTT, the concept of physical frailty is translated with a Short Physical Performance Battery score of ≥3 and ≤9. Concurrently, sarcopenia is defined according to the recent definitions of low muscle mass proposed by the Foundation for the National Institutes of Health-Sarcopenia Project. Given the preventive purpose of SPRINTT, older persons with mobility disability (operationalized as incapacity to complete a 400-m walk test within 15 min; primary outcome of the trial) at the baseline are not included within the diagnostic spectrum of PF&S.

Sarcopenia, the age-dependent loss of muscle mass and function, is a common condition among older adults, and is associated with several adverse health outcomes. Owing to the impact of sarcopenia on quality of life, disability and mortality, a greater awareness is necessary in order to correctly identify the condition both in community and geriatric settings. Research on sarcopenia prevention and treatment is developing quickly, but many questions are still unanswered. The core of the sarcopenia condition involves quantitative and qualitative losses of skeletal muscle. These two dimensions should therefore be considered when designing and testing preventive and therapeutic interventions. The recently released operationalization of sarcopenia by the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project allows for the framing of an objective, standardized, and clinically relevant condition, which should facilitate its translation into the clinical arena as well as its adoption by public health and regulatory agencies. Such a conceptualization might eventually encourage key stakeholders to combine their efforts in approaching the sarcopenia condition. Bearing these considerations in mind, the "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" project has operationalized a specific condition, named physical frailty and sarcopenia (PF&S), characterized by the combination of low physical performance (based on the Short Physical Performance Battery) and low muscle mass (according to the FNIH cut-points). A randomized controlled trial will be conducted to evaluate the efficacy of a multi-component intervention for preventing mobility disability and other adverse health outcomes in older adults with PF&S.

Physical frailty (PF) and sarcopenia are major health issues in geriatric populations, given their high prevalence and association with several adverse outcomes. Nevertheless, the lack of an univocal operational definition for the two conditions has so far hampered their clinical implementation. Existing definitional ambiguities of PF and sarcopenia, together with their complex underlying pathophysiology, also account for the absence of robust biomarkers that can be used for screening, diagnostic and/or prognostication purposes. This review provides an overview of currently available biological markers for PF and sarcopenia, as well as a critical appraisal of strengths and weaknesses of traditional procedures for biomarker development in the field. A novel approach for biomarker identification and validation, based on multivariate methodologies, is also discussed. This strategy relies on the multidimensional modeling of complementary biomarkers to cope with the phenotypical and pathophysiological complexity of PF and sarcopenia. Biomarkers identified through the implementation of multivariate strategies may be used to support the detection of the two conditions, track their progression over time or in response to interventions, and reveal the onset of complications (e.g., mobility disability) at a very early stage.

The sustainability of health and social care systems is threatened by a growing population of older persons with heterogeneous needs related to multimorbidity, frailty, and increased risk of functional impairment. Since disability is difficult to reverse in old age and is extremely burdensome for individuals and society, novel strategies should be devised to preserve adequate levels of function and independence in late life. The development of mobility disability, an early event in the disablement process, precedes and predicts more severe forms of inability. Its prevention is, therefore, critical to impede the transition to overt disability. For this reason, the Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies (SPRINTT) project is conducting a randomized controlled trial (RCT) to test a multicomponent intervention (MCI) specifically designed to prevent mobility disability in high-risk older persons. SPRINTT is a phase III, multicenter RCT aimed at comparing the efficacy of a MCI, based on long-term structured physical activity, nutritional counseling/dietary intervention, and an information and communication technology intervention, versus a healthy aging lifestyle education program designed to prevent mobility disability in 1500 older persons with physical frailty and sarcopenia who will be followed for up to 36 months. The primary outcome of the SPRINTT trial is mobility disability, operationalized as the inability to walk for 400 m within 15 min, without sitting, help of another person, or the use of a walker. Secondary outcomes include changes in muscle mass and strength, persistent mobility disability, falls and injurious falls, disability in activities of daily living, nutritional status, cognition, mood, the use of healthcare resources, cost-effectiveness analysis, quality of life, and mortality rate. SPRINTT results are expected to promote significant advancements in the management of frail older persons at high risk of disability from both clinical and regulatory perspectives. The findings are also projected to pave the way for major investments in the field of disability prevention in old age.

The identification of cost-effective interventions that improve the health status and prevent disability in old age is one of the most important public health challenges. Regular physical activity is the only intervention that has consistently been shown to improve functional health and energy balance and to reduce the risk of cardiovascular disease, stroke, diabetes, several cancers, depression and falls. In advanced age, physical activity is also effective at mitigating sarcopenia, restoring robustness, and preventing/delaying the development of disability. On the other hand, physical inactivity is recognized as one of the leading causes of several chronic degenerative diseases and is also a major contributing factor to sarcopenia and functional disability. This compelling evidence has prompted the World Health Organization to recommend engaging in regular physical activity throughout one's life course. The present review summarizes the available evidence in support of physical activity as a remedy against physical frailty and sarcopenia. The relevant pathways through which the benefits of physical activity are conveyed are also discussed.

Objective: Sarcopaenia and physical function impairment may have a greater effect on survival than other clinical characteristics, including multimorbidity. In this study, we evaluated the impact of sarcopaenia on all-cause mortality and the interaction among muscle loss, physical function impairment and multimorbidity on mortality risk over 10 years in older community-dwellers., Design: Prospective cohort study., Setting: Population-based study., Participants: All persons aged 80+ years living in the community in the Sirente geographic area (L'Aquila, Italy) (n=364). Participants were categorised in the sarcopaenic or non-sarcopaenic group based on the European Working Group on Sarcopenia in Older People criteria., Primary and Secondary Outcome Measures: (1) All-cause mortality over 10 years according to the presence of sarcopaenia and (2) impact of physical function impairment, assessed using the Short Physical Performance Battery (SPPB), and multimorbidity on 10-year mortality risk in persons with sarcopaenia., Results: Sarcopaenia was identified in 103 participants (29.1%). A total of 253 deaths were recorded over 10 years: 90 among sarcopaenic participants (87.4%) and 162 among non-sarcopaenic persons (65.1%; p<0.001). Participants with sarcopaenia had a higher risk of death than those without sarcopaenia (HR=2.15; 95% CI 1.02 to 4.54). When examining the effect of sarcopaenia and physical function impairment on mortality, participants with low physical performance levels showed greater mortality. Conversely, the mortality risk was unaffected by multimorbidity., Conclusions: Our findings show that physical function impairment, but not multimorbidity, is predictive of mortality in older community-dwellers with sarcopaenia. Hence, in sarcopaenic older persons, interventions against functional decline may be more effective at preventing or postponing negative health outcomes than those targeting multimorbidity., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Sarcopenia has been proposed as a potentially amenable factor impacting the clinical outcomes of hip-fractured elderly. The identification of specific biological targets is therefore crucial to developing pharmacological interventions against age-related muscle wasting. The present work reports promising preliminary data on the association between alterations of myocyte quality control (MQC) signaling and sarcopenia in old patients with hip fracture., Methods: Twenty-five elderly hip-fractured patients (20 women and 5 men; mean age 84.9±1.65years) were enrolled as part of the Sarcopenia in HIp FracTure (SHIFT) study. Intraoperative biopsies of the vastus lateralis muscle were obtained and assayed for the expression of a set of MQC signaling proteins. The presence of sarcopenia was established according to the European Working Group on Sarcopenia in Older People (EWGSOP) criteria, with bioelectrical impedance analysis used for fat-free mass estimation., Results: Sarcopenia was identified in 10 patients (40%). Protein expression of the mitochondrial fusion factor mitofusin (Mfn) 2 and the autophagy mediator microtubule-associated protein 1 light chain 3B (LC3B) was significantly lower in patients with sarcopenia compared with non-sarcopenic controls. No differences between groups were observed for Mfn1, optic atrophy protein 1 (OPA1), fission protein 1 (Fis1), and the master regulator of mitochondrial biogenesis peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)., Conclusion: Data from this exploratory study show that a reduced expression of the mitochondrial fusion factor Mfn2 and the autophagy mediator LC3B is associated with sarcopenia in old hip-fractured patients. Future larger-scale studies are needed to corroborate these preliminary findings and determine whether MQC pathways may be targeted to improve muscle health and promote functional recovery in old patients with hip fracture., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The C-terminal agrin fragment (CAF), a circulating byproduct of neuromuscular junction disassembly, has been proposed as a possible biomarker for sarcopenia. However, its validity in "real-world", multimorbid older persons is currently unknown. The present study was undertaken to verify if serum CAF levels were associated with sarcopenia in a population of old and very old persons living in the community., Methods: Data were from the ilSIRENTE Aging and Longevity Study, a prospective cohort study conducted in all persons aged 80years and older residing in the Sirente geographic area (Italy; n=332). The identification of sarcopenia was based on the criteria elaborated by the European Working Group on Sarcopenia in Older People (EWGSOP). Serum levels of CAF were determined using a commercial ELISA kit., Results: Sarcopenia was identified in 101 participants (30.8%). Serum levels of CAF were significantly higher in older adults with sarcopenia compared with non-sarcopenic participants (96.99±5.40pmol/L vs. 76.54±2.15pmol/L; p<0.001). The association remained significant in both genders after adjustment for several possible confounding factors, including age, cognition, disability status, body mass index, congestive heart failure, lung diseases, diabetes, renal failure, and plasma levels of C-reactive protein and interleukin 6., Conclusions: Our results obtained from a fairly large sample of old and very old, multimorbid community-dwellers show that elevated serum CAF levels are associated with sarcopenia, independent of age, gender and several clinical, functional, anthropometric, and biochemical variables. The determination of serum CAF concentration may therefore be proposed as a simple screening test for sarcopenia in the community., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Physical function decreases with aging, which may result in adverse outcomes (eg, disability, loss of independence, institutionalization, death). Physical function impairment is a common trait of frailty and sarcopenia. These two conditions, albeit highly common, have not yet received a unique operational definition, which has impeded their implementation in standard practice. Here, we introduce a conceptual model in which sarcopenia is proposed as the biological substrate and the pathway whereby the consequences of physical frailty develop. This conceptualization may open new venues for the design of interventions against physical frailty and promote the translation of findings to the clinical arena., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Serum concentrations of the C-terminal fragment of agrin (CAF), a component of the neuromuscular junction (NMJ), are elevated in older community-dwellers with sarcopenia. Whether CAF may be used as a marker for muscle wasting in the presence of NMJ mechanical damage is presently unknown. The present study was undertaken to verify if serum CAF levels were associated with sarcopenia in older hip fractured patients., Methods: Analyses were conducted in older adults hospitalized for traumatic hip fracture. The presence of sarcopenia was established according to the European Working Group on Sarcopenia in Older People criteria, with bioelectrical impedance analysis used for muscle mass estimation. Serum levels of CAF were determined using a commercial ELISA kit., Results: Among 42 hip fractured patients (age 83.7±8.6 years, 76.2% women), sarcopenia was diagnosed in 7 individuals (16.7%). Serum CAF levels were significantly higher in sarcopenic relative to non-sarcopenic patients (172.2±47.5 pM vs. 93.1±44.0 pM; p<0.001). The association remained significant in both genders after adjustment for several potential confounders., Conclusion: Elevated serum CAF concentrations are associated with sarcopenia in older adults with hip fracture. The determination of serum CAF levels could therefore serve to identify a subset of hip fractured patients at especially high risk for adverse health outcomes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Sarcopenia is a common condition in older and frail populations, and it has been associated with adverse health outcomes. However, impact of sarcopenia on mortality in hospitalized older adults has rarely been evaluated. Aim of the present study was to investigate the association between sarcopenia and mortality during hospital stay and at 1 year after discharge in older individuals admitted to acute care wards., Methods: This is a multicentre observational study involving 770 in-hospital patients. Muscle mass was quantified with the bioelectrical impedance analysis. The diagnosis of sarcopenia was based on the algorithm proposed by the European Working Group on Sarcopenia in Older People (EWGSOP). After discharge, participants were followed for 1 year. Mortality was assessed during hospital stay and during 1-year follow-up., Results: Within the 770 participants (mean age: 81 ± 7 years, 56% women), sarcopenia was present in 214 (28%) of them, 22 participants died during hospital stay, and 113 in the year after discharge. Participants with sarcopenia had a significantly higher in-hospital (6% vs 2%; p = .007) and 1-year mortality (26% vs 14%; p < .001) as compared with participants without sarcopenia. After adjusting for potential confounders, sarcopenia resulted significantly associated with in-hospital (hazard ratio: 3.45; 95% CI: 1.35-8.86) and 1-year mortality (hazard ratio: 1.59; 95% CI: 1.10-2.41)., Conclusions: Sarcopenia is a prevalent condition among older adults admitted to acute care wards and it is associated with increased short- and long-term mortality in hospitalized older adults., (© The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose of Review: Although prolongation of life is a significant public health aim, at the same time the extended life should involve preservation of the capacity to live independently. Consequently, the identification of cost-effectiveness interventions to prevent frailty is one of the most important public health challenges. In the present review, we present the available evidence regarding the impact of physical exercise on the components of frailty syndrome and, in particular, as a remedy for sarcopenia., Recent Findings: Resistance exercise training is more effective in increasing muscle mass and strength, whereas endurance exercises training is superior for maintaining and improving maximum aerobic power. Based on these evidences, recommendations for adult and frail older people should include a balanced program of both endurance and strength exercises, performed on a regular schedule (at least 3 days a week)., Summary: Regular exercise is the only strategy found to consistently prevent frailty and improve sarcopenia and physical function in older adults. Physical exercises increase aerobic capacity, muscle strength and endurance, by ameliorating aerobic conditioning and/or strength. In older patients, exercise and physical activity produce at least the same beneficial effects observed in younger individuals.

In the literature, different criteria have been validated to identify frail older subjects, which mainly refer to two conceptual models: the cumulative deficit approach proposed by Rockwood and the Physical Frailty (PF) phenotype proposed by Fried. Both models have received empirical validation. Nevertheless, the frailty phenotype is the most widely used and presents a characterized pathophysiologic background. The PF condition depicted by the frailty phenotype has shown to be predictive of major negative health-related outcomes, including mobility disability, disability for activities of daily living, institutionalization, and mortality. At the same time, it cannot be ignored that the PF phenotype presents substantial overlaps with sarcopenia, "a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes such as physical disability, poor quality of life and death". In fact, many of the adverse outcomes of frailty are probably mediated by sarcopenia. Therefore, sarcopenia may be considered both as the biological substrate for the development of PF and the pathway through which the negative health outcomes of frailty ensue. Although PF encompasses only a part of the frailty spectrum, the identification of a definite biological basis (i.e., skeletal muscle decline) opens new venues for the development of interventions to slow or reverse the progression of this condition. Here, we present a novel conceptualisation of PF which will possibly promote significant advancements over the traditional approaches to this syndrome by enabling the precise operationalisation of the condition, a clear identification of the affected population and the rapid translation of findings to the clinical arena.

Background: Recently, a great deal of attention has been paid to the role of inflammatory processes in the pathophysiology of sarcopenia. The aim of the present study was to examine the relationship between NSAID use and sarcopenia in a large sample of community-dwelling elderly people aged 80 years or older., Methods: Data are from the baseline evaluation of 354 individuals enrolled in the ilSIRENTE Study. Following the recommendations of the European Working Group on Sarcopenia in Older People (EWGSOP), the diagnosis of sarcopenia was established on the basis of low muscle mass plus either low muscle strength or low physical performance. The relationship between NSAID use and sarcopenia was estimated by deriving odds ratios (ORs) from multiple logistic regression models considering sarcopenia as the dependent variable., Results: Nearly 12% (n = 44) of the study sample used NSAIDs. Using the EWGSOP-suggested algorithm, 103 individuals (29.1%) with sarcopenia were identified. Ninety-nine (31.9%) participants were affected by sarcopenia among non-NSAID users compared with 4 participants (9.1%) among NSAID users (P < .001). Compared with all nonusers, NSAID users had a nearly 80% lower risk of being affected by sarcopenia (OR 0.21, 95% CI 0.07-0.61). After adjusting for potential confounders, NSAID users had a lower risk of sarcopenia compared with nonusers (OR 0.26, 95% CI: 0.08-0.81)., Conclusions: The results are consistent with the hypothesis that long-term NSAID use might have a protective effect against the loss of muscle mass and function. Interventions able to reduce inflammation-related adverse outcomes at muscle level may be warranted., (Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: There is increasing evidence that anorexia of aging can cause physical and mental impairment. The aim of the present study was to evaluate the relationship between anorexia and sarcopenia in elderly persons aged 80 years or older., Methods: Data are from the baseline evaluation of 354 subjects enrolled in the ilSIRENTE study. The ilSIRENTE study is a prospective cohort study performed in the mountain community living in the Sirente geographic area (L'Aquila, Abruzzo) in Central Italy. We defined anorexia as the presence of loss of appetite and/or lower food intake. According to the European Working Group on Sarcopenia in Older People (EWGSOP) criteria, diagnosis of sarcopenia required the documentation of low muscle mass plus the documentation of either low muscle strength or low physical performance. The relationship between anorexia and sarcopenia was estimated by deriving odds ratios from the multiple logistic regression models considering sarcopenia as the dependent variable., Results: Nearly 21 % of the study sample showed symptoms of anorexia. Using the EWGSOP-suggested algorithm, 103 subjects (29.1 %) with sarcopenia were identified. Thirty-four (46.6 %) participants were affected by sarcopenia among subjects with anorexia compared to 69 subjects [24.6 %] without anorexia (p < 0.001). After adjusting for potential confounders including age, gender, functional and cognitive impairment, physical activity, urinary incontinence, comorbidity, congestive heart failure, COPD, depression, anti-cholinergic drugs, and TNF-α plasmatic levels, participants with anorexia had a higher risk of sarcopenia compared with non-anorexic subjects (HR 1.88, 95 % CI 1.01-3.51)., Conclusions: Anorexia is common among community-dwelling older subjects in Italy. Our results suggest that among old-old subjects, anorexia is independently associated with sarcopenia.

Muscle loss during aging and disuse is a highly prevalent and disabling condition, but knowledge about cellular pathways mediating muscle atrophy is still limited. Given the postmitotic nature of skeletal myocytes, the maintenance of cellular homeostasis relies on the efficiency of cellular quality control mechanisms. In this scenario, alterations in mitochondrial function are considered a major factor underlying sarcopenia and muscle atrophy. Damaged mitochondria are not only less bioenergetically efficient, but also generate increased amounts of reactive oxygen species, interfere with cellular quality control mechanisms, and display a greater propensity to trigger apoptosis. Thus, mitochondria stand at the crossroad of signaling pathways that regulate skeletal myocyte function and viability. Studies on these pathways have sometimes provided unexpected and counterintuitive results, which suggests that they are organized into a complex, heterarchical network that is currently insufficiently understood. Untangling the complexity of such a network will likely provide clinicians with novel and highly effective therapeutics to counter the muscle loss associated with aging and disuse. In this review, we summarize the current knowledge on the mechanisms whereby mitochondrial dysfunction intervenes in the pathogenesis of sarcopenia and disuse atrophy, and highlight the prospect of targeting specific processes to treat these conditions.

Background and Aims: sarcopenia has been indicated as a reliable marker of frailty and poor prognosis among the oldest individuals. We evaluated the impact of sarcopenia on the risk of all-cause death in a population of frail older persons living in community., Methods: we analysed data from the Aging and Longevity Study, a prospective cohort study that collected data on all subjects aged 80 years and older residing in the Sirente geographic area (n = 364). The present analysis was conducted among those subjects who were between 80 and 85 years of age at the time of the baseline assessment (n = 197). The main outcome measure was all-cause mortality over 7-year follow-up. According to the European Working Group on Sarcopenia in Older People (EWGSOP) criteria, the diagnosis of sarcopenia required the documentation of low muscle mass and the documentation of either low muscle strength or low physical performance. Cox proportional regression models were used to estimate crude and adjusted hazard ratios and 95% confidence intervals of death by the presence of sarcopenia., Results: using the EWGSOP-suggested criteria, 43 subjects with sarcopenia (21.8%) were identified. During the 7-year follow-up, 29 (67.4%) participants died among subjects with sarcopenia compared with 63 subjects (41.2%) without sarcopenia (P < 0.001). After adjusting for potential confounders including age, gender, education, activities of daily living (ADL) impairment, body mass index, hypertension, congestive heart failure, chronic obstructive pulmonary disease, number of diseases, TNF-α, participants with sarcopenia had a higher risk of death for all causes compared with non-sarcopenic subjects (HR: 2.32, 95% CI: 1.01-5.43)., Conclusions: our results obtained from a representative sample of very old and frail subjects show that sarcopenia is associated with mortality, independently of age and other clinical and functional variables.

Background & Aims: Sarcopenia has been indicated as a reliable marker of frailty and poor prognosis among the oldest individuals. We evaluated the relationship between sarcopenia and 2-year risk of falls in a population of persons aged 80 years or older., Methods: Data are from the baseline and follow-up evaluations of the Aging and Longevity Study in the Sirente Geographic Area (ilSIRENTE Study) (n=260). According to the European Working Group on Sarcopenia in Older People (EWGSOP), sarcopenia was diagnosed in presence of low muscle mass (mid-arm muscle circumference) plus either low muscle strength (hand grip) or low physical performance (4-m walking speed). The primary outcome measure was the incident falls during the follow-up period of 2 years. The relationship between sarcopenia and incident falls was estimated by deriving hazard ratios (HRs) from multiple logistic regression models considering the dependent variable of interest at least one fall during the follow-up period., Results: Sixty-six participants (25.4%) were identified as affected by sarcopenia. Eighteen out of 66 (27.3%) participants with sarcopenia and 19 out of 194 (9.8%) without sarcopenia reported incident falls during the two-year follow-up of the study (p<0.001). After adjusting for age, gender, cognitive impairment, ADL impairment, sensory impairments, BMI, depression, physical activity, cholesterol, stroke, diabetes, number of medications, and C-reactive protein, participants with sarcopenia had a higher risk of incident falls compared with non sarcopenic subjects (adjusted hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.25-8.29)., Conclusions: The present study suggests that sarcopenia - assessed using the EWGSOP algorithm - is highly prevalent among elderly persons without gender differences (25%). Sarcopenic participants were over three times more likely to fall during a follow-up period of 2 years relative to non sarcopenic individuals, regardless of age, gender and other confounding factors., (Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background and Aims: Sarcopenia has been indicated as a reliable marker of frailty and poor prognosis among the oldest individuals. At present, no data are available on sarcopenia in the nursing home population. The aim of the current study was to explore the relationship between sarcopenia and all-cause mortality in a population of elderly persons aged 70 years and older living in a nursing home in Italy., Methods: This study was conducted among all subjects (n = 122) aged 70 years and older who lived in the teaching nursing home of Catholic University of Rome between August 1, 2010, and September 30, 2010. According to the European Working Group on Sarcopenia in Older People (EWGSOP), sarcopenia was diagnosed in presence of low muscle mass plus either low muscle strength or low physical performance. The primary outcome measure was survival after 6 months., Results: Forty residents (32.8%) were indentified as affected by sarcopenia. This condition was more common in men (68%) than in women (21%). During the follow-up period, 26 (21.3%) patients died. After adjusting for age, gender, cerebrovascular diseases, osteoarthritis, chronic obstructive pulmonary disease, activity of daily living impairment, and body mass index, residents with sarcopenia were more likely to die compared with those without sarcopenia (adjusted hazard ratio 2.34; 95% confidence interval 1.04-5.24)., Conclusions: The present study suggests that among subjects living in a nursing home, sarcopenia is highly prevalent and is associated with a significantly increased risk of all-cause death. The current findings support the possibility that sarcopenia has an independent effect on survival among nursing home residents., (Copyright © 2012 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Sarcopenia has been indicated as a reliable marker of frailty and poor prognosis among the oldest individuals. At present, there are no data on sarcopenia in nursing home population. We evaluated the prevalence of sarcopenia and its association with functional and clinical status in a population of elderly persons aged 70 years and older living in nursing homes., Methods: This study was conducted selecting all the participants (n = 122) living in the teaching nursing homes of Catholic University of Rome who were aged 70 years and older from August 1, 2010, to September 30, 2010. The European Working Group on Sarcopenia in Older People (EWGSOP) criteria were adopted. Accordingly, diagnosis of sarcopenia required the documentation of low muscle mass plus the documentation of either low muscle strength or low physical performance., Results: Forty residents (32.8%) were identified as affected by sarcopenia. The multivariate logistic regression analysis showed a high increase in risk of sarcopenia for male residents (odds ratio [OR] 13.39; 95% confidence interval [CI] 3.51-50.63) and for residents affected by cerebrovascular disease (OR 5.16; 95% CI 1.03-25.87) or osteoarthritis (OR 7.24; 95% CI 2.02-25.95). Residents who had a body mass index higher than 21 kg/m(2) had a lower risk to be sarcopenic (OR 0.76; 95% CI 0.64-0.90) relative to those with body mass index less than 21 kg/m(2). Similarly, sarcopenia was less likely to be present among participants involved in leisure physical activity for 1 hour or more per day (OR 0.40; 95% CI 0.12-0.98)., Conclusions: The present study suggests that among participants living in nursing homes, sarcopenia is highly prevalent and it is more represented among male residents (68%) than among female residents (21%). Our findings support the hypothesis that muscle mass is strongly associated with nutritional status and physical activity in nursing homes, too.

Background: Sarcopenia, the age-related loss of muscle mass and function, represents a relevant public health issue due to its high prevalence and detrimental consequences. While the exact mechanisms underlying the pathogenesis of sarcopenia are not clear, growing experimental evidence indicates that progressive myonuclear elimination over the course of aging via an apoptosis-like process may represent a converging mechanism through which muscle atrophy and loss of physical function develop. Notably, the proapoptotic environment taking place in aged muscle appears amenable to interventions., Objective: We aimed at providing (1) an overview of signaling pathways of apoptosis relevant to sarcopenia, and (2) a review of the literature supporting myocyte apoptosis as a target for interventions against muscle aging., Methods: We summarized findings from studies focused on skeletal myocyte apoptosis as a mechanism in the development of sarcopenia and reports supporting myonuclear apoptosis as a target for interventions against age-related muscle loss., Results: Advanced age is associated with increased signaling through extrinsic and intrinsic apoptotic pathways in skeletal myocytes. In contrast, downregulation of myocyte apoptosis through calorie restriction, exercise training, hormonal supplementation, drugs (e.g. angiotensin-converting enzyme inhibitors, acetaminophen, antimyostatin antibodies), nutraceuticals or genetic interventions (e.g. PGC-1α overexpression) is linked with preservation of muscle integrity and improved physical performance in late life. Preliminary data also indicate that skeletal myocyte apoptotic signaling may be downregulated by compounds, such as resveratrol, with calorie restriction-mimicking properties. Whether exercise mimetics exert a similar effect has not yet been investigated., Conclusions: Available evidence suggests that targeting myonuclear apoptosis might provide novel and effective therapeutic tools to combat sarcopenia. Further research is required to definitely establish if downregulating myonuclear apoptosis is effective in maintaining muscle mass and function in late life, identify the most relevant apoptotic pathway(s) to target, and determine the optimal timing for intervening., (Copyright © 2011 S. Karger AG, Basel.)

Physical exercise is the most effective intervention against sarcopenia of aging; however, the cellular and molecular mechanisms mediating training-induced adaptations are not yet completely understood. Furthermore, it is unclear whether exercise training initiated late in life affects myocyte anabolic signaling in a dose-dependent manner. Hence, we sought to investigate the effects of treadmill exercise and training frequency on anabolic pathways, including insulin signaling, in the skeletal muscle of old rats. Aged (14-16-month-old) male Wistar rats were trained on a treadmill for 3 (EX3) or 5 days/week (EX5) during 8 weeks and compared with age-matched sedentary controls (SED). Four-month-old rats were used as young controls (YC). Protein expression levels of insulin receptor (IR), insulin receptor substrate 1 (IRS-1), activated (phosphorylated) mammalian target of rapamycin (p-mTOR) and glucose transporter GLUT4 were determined in quadriceps muscle extracts via immunoblotting. Mitochondrial cytochrome c oxidase (COX) activity was assessed by histochemical staining, while electron microscopy was employed to quantify the sarcomere volume (V(src)). Body weight (BW) increased, whereas muscle weight (MW) and V(src) decreased with age. EX5, but not EX3 increased MW and V(src), without affecting BW. The expression of IR and GLUT4 was higher in SED rats relative to the YC group. Conversely, protein levels of IRS-1 and p-mTOR as well as COX activity were reduced in advanced age. Compared with SED rats, EX3 animals displayed reduced IR expression and increased IRS-1 levels and COX activity. The expression of GLUT 4 and p-mTOR was unaffected by EX3. EX5 up-regulated IRS-1 and p-mTOR expression and COX activity, while decreasing GLUT4 levels, with no effect on IR expression. In summary, substantial impairments in muscle anabolic pathways, including insulin signaling, were detected in aged sedentary rats. These changes were ameliorated by exercise training, concomitant with improvements in muscle trophism. Benefits were more evident in rats trained for 5 days/week, suggesting that physical exercise initiated late in life affects anabolic signaling in a dose-dependent manner., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background & Aims: Sarcopenia has been indicated as a reliable marker of frailty and poor prognosis among the oldest individuals. We evaluated the relationship between midarm muscle circumference (MAMC) and physical performance, muscle strength, functional status and survival in persons aged 80 years or older., Methods: Data are from the baseline evaluation of the Aging and Longevity Study in the Sirente Geographic Area (ilSIRENTE Study) (n = 357). MAMC was calculated taking into account the mid upper arm circumference and the triceps skinfold thickness of the right arm. Physical performance was assessed using the physical performance battery score, which is based on three timed tests: 4-m walking speed test, the balance test and the chair stand test. Analyses of covariance were performed to evaluate the relationship between different MAMC levels and physical function. Cox proportional regression models were used to estimate crude and adjusted hazard ratios and 95% confidence intervals of death by MAMC levels., Results: After adjustment for potential confounders - which included age, gender, living alone, sensory impairments (hearing and vision), body mass index, albumin and cholesterol - physical performance and function (which were measured using the 4-m walking speed test, the Short Physical Performance Battery score, the hand grip strength), improved significantly as MAMC increased. Compared with those in the low MAMC tertile, subjects in the high MAMC tertile had a lower risk of death (adjusted hazard ratio (HR) 0.45; 95% Confidence Interval (CI) 0.23-0.87)., Conclusions: The present study suggests that among community-dwelling old-old subjects muscle mass may be positively related to functional performance and survival., (Copyright 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Accelerated apoptosis in skeletal muscle is increasingly recognized as a potential mechanism contributing to the development of sarcopenia of aging and disuse muscle atrophy. Given their central role in the regulation of apoptosis, mitochondria are regarded as key players in the pathogenesis of myocyte loss during aging and other atrophying conditions. Oxidative damage to mitochondrial constituents, impaired respiration and altered mitochondrial turnover have been proposed as potential triggering events for mitochondrial apoptotic signaling. In addition, iron accumulation within mitochondria may enhance the susceptibility to apoptosis during the development of sarcopenia and possibly acute muscle atrophy, likely through exacerbation of oxidative stress. Mitochondria can induce myocyte apoptosis via both caspase-dependent and independent pathways, although the apoptogenic mediators involved may be different depending on age, muscle type and specific atrophying conditions. Despite the considerable advances made, additional research is necessary to establish a definite causal link between apoptotic signaling and the development of sarcopenia and acute atrophy. Furthermore, a translational effort is required to determine the role played by apoptosis in the pathogenesis of sarcopenia and disuse-induced muscle loss in human subjects., (Published by Elsevier B.V.)

Muscle wasting and cachexia are the ultimate consequence of aging and a variety of acute and chronic illnesses. Significant efforts are made by many stakeholders to develop effective therapies. An important aspect of successful therapeutic development research is a common nomenclature for effective communication between researchers and clinicians, to the public, and also with regulatory bodies. Despite several efforts to develop consensus definitions for cachexia and sarcopenia, including such new terms for muscle wasting as myopenia, a common conceptual approach and acceptable vocabulary and classification system are yet to be established. Notwithstanding the potential need to translate such disease definitions and terminologies into different languages, we advocate the use of the term "muscle wasting" as the unifying entity that represents the single most common disease process across a large spectrum of cachexia and in sarcopenia-associated disorders. In this paper, we outline a first proposal for the disease nomenclature and classification of "Muscle Wasting Diseases." This concept can be applied in acute and chronic disease settings. It is pertinent for wasting diseases, cachexia, and sarcopenia of any severity and due to any underlying illness. The concept of muscle wasting disease underscores the most common denominator of the underlying wasting processes, i.e., muscle wasting, without ignoring the advanced disease states that are also accompanied by fat tissue wasting. The term muscle wasting disease is easily understood by both the scientific community and the lay public. This may promote its general use and efforts to heighten education and awareness in the field.

A fall is an event where a person unintentionally and traumatically finds themselves on the floor or a lower level. Falls are very common, especially in the older adult population. One in four people falls at least once a year after age 65. Because of falls, there can be injuries, whereby there can be an impairment of health status. Fractures, reduced mobility, disability, and the need for institutionalization are potential consequences after falls. In older adult patients, especially frail ones, these types of complications are more common. There are several risk factors for falls. Falls generally result from a combination of factors operating simultaneously. Sarcopenia, cognitive impairment, or poly-pharmacotherapy are just a few examples of risk factors that are common in the older people. Through careful clinical evaluation, it is possible to identify risk factors and conditions predisposing to falls. In some cases, it is possible to correct these factors. Several types of treatment are available to restore the health status before the fall and prevent subsequent falls. Using multi-component interventions, the risk of falls can be effectively reduced. Aware that this review will not be exhaustive of such a broad topic, the purpose of this narrative review is to summarize relevant and recent evidence in the current literature to encapsulate fall-related risk factors, risk identification, fall prevention, and management, including various rehabilitation techniques. This article conforms to the Scale for Assessment of Narrative Review Articles (SANRA) guidelines. [ABSTRACT FROM AUTHOR]