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Background: Poor sleep quality may contribute to sarcopenia, but evidence remains sparse. This retrospective cross-sectional study investigated the association between subjective sleep quality and probable sarcopenia in a cohort of community-dwelling older adults enrolled in the Longevity Check-Up 8+ study., Methods: Participants were asked about their sleep quality over the past month, with four possible options ("very good", "quite good", "quite bad", very bad"). For the analysis, participants were grouped into good or bad sleep quality categories. Probable sarcopenia was operationalized according to handgrip strength values < 27 kg for men and < 16 kg for women. Logistic regression models were used to explore the relationship between sleep quality and probable sarcopenia., Results: 1971 participants were included in the analysis (mean age 73.4 ± 6.2 years, 50.0 % women). Bad sleep quality was reported by 28.3 % of participants and was more prevalent among women, physically inactive individuals, and those with dyslipidemia. Probable sarcopenia was more prevalent in participants with bad sleep quality (23.8 % vs. 18.7 %, p = 0.012). Logistic regression revealed that bad sleep quality was significantly associated with increased odds of probable sarcopenia in both unadjusted (odds ratio [OR] 1.36, 95 % confidence interval [CI] 1.07-1.72, p = 0.010) and fully adjusted models (OR 1.40, 95 % CI 1.08-1.81, p = 0.011)., Conclusions: Poor sleep quality is associated with increased likelihood of probable sarcopenia in older adults. This finding highlights the importance of addressing sleep quality in interventions aimed at preventing sarcopenia and promoting healthy aging., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The present study examined the associations between the dietary intake of polyunsaturated fatty acids (PUFAs), physical function, and the prevalence of sarcopenia in Italian community-dwelling older adults., Design: Cross-sectional study., Setting: Unconventional settings across Italy (e.g., exhibitions, health promotion campaigns)., Participants: Older adults (65+ years) who provided a written informed consent., Methods: Physical function was evaluated according to isometric handgrip strength (IHG) and 5-time sit-to-stand (5STS) performances. Muscle power parameters were estimated based on 5STS values. Sarcopenia was operationalized according to the presence of low physical function (IHG or 5STS) plus low appendicular skeletal muscle mass (ASM), estimated according to calf circumference. A 12-item food questionary was used to estimate the dietary intake of PUFAs, which included omega-3 (α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid) and omega-6 fatty acids., Results: Multiple linear regression results indicate negative and significant associations between the dietary intake of α-linolenic acid and muscle power, and between docosahexaenoic acid consumption and ASM. No significant associations were found between PUFAs-related variables and sarcopenia., Conclusions: Results of the present study indicate that PUFAs-related variables were negatively and significantly associated with physical function and body composition in older adults. Nevertheless, no significant associations were found with sarcopenia. These findings suggest that a more detailed analysis of covariates should be conducted in future investigations that aim to examine the associations between the dietary intake of PUFAs and sarcopenia-related parameters., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: We compared the performance of SARC-F, SARC-CalF, calf circumference (CC), and body mass index (BMI)-adjusted CC for sarcopenia case-finding in community-dwelling older adults., Methods: Data of Finnish participants (women/men n = 192/36, mean age (SD) of 76.9 (4.8) years) recruited in the SPRINTT trial (NCT02582138) were used. Sarcopenia was determined as a combination of low muscle function (chair-stand-test) and low appendicular lean mass (ALM) detected by whole-body dual-energy X-ray absorptiometry. Associations of case-finding tools with sarcopenia were analysed using ROC curves and logistic regression., Results: The rates of probable and confirmed sarcopenia were 95% and 18% in women and 94% and 36% in men, respectively. Performance of CC for sarcopenia (women AUC 0.85 [95% CI 0.78-0.92]/ men 0.85 [95% CI 0.71-1.0]) was superior to that of other tools; (AUC in women/men for SARC-F was 0.57/0.50, for SARC-CalF 0.76/0.79, and for BMI-adjusted CC 0.68/0.66). The best performance was found for a CC cut-off point of ≤ 34 cm in women with sensitivity/specificity 82.4/75.3% and ≤ 36 cm in men with sensitivity/specificity 76.9/87.0%. For each cm decrease in CC, adjusted for age and BMI, there was a 30% increase in the odds of sarcopenia in women (OR 1.30, 95% CI 1.09─1.56). Although there was a similar pattern in men, the results did not reach statistical significance (OR 1.34, 95% CI 0.84- 2.14)., Conclusions: CC was superior to other tools for sarcopenia case-finding. The best performance was found for a CC cut-off point of ≤ 34 cm in women and ≤ 36 cm in men., Competing Interests: Declarations. Conflict of interest: The authors report no competing interests. Ethical statements: The study protocol was approved by the HUS Regional Committee on Medical Research Ethics in Finland (Dnro 244/13/03/01/2015) and by the regional ethics committees of all participating institutions. The study was conducted in compliance with the Declaration of Helsinki and its later amendments. Informed consent: Written informed consent was obtained from all participants that were screened for eligibility, including consent to use information acquired from the screening phase of the trial., (© 2024. The Author(s).)

Sarcopenia is associated with structural, ultrastructural, and molecular abnormalities of skeletal muscle. Mitochondrial dysfunction is a pivotal factor involved in muscle aging and sarcopenia. Mitochondrial bioenergetics are significantly reduced in muscles of older adults which is associated with whole-body aerobic capacity, muscle strength, and physical performance. Transcriptional profiling of muscle samples from older adults also revealed inverse correlations between gene expression patterns of autophagy and mitophagy and muscle volume and physical performance. This is in line with the proposition that mitochondrial quality control (MQC) processes are key to organellar and tissue health. MQC encompasses mitochondrial biogenesis, dynamics, and mitophagy. The latter has recently been included among the hallmarks of aging and alterations in MQC have been associated with chronic sterile inflammation as well as muscle atrophy and dysfunction. Several biomarkers spanning MQC, inflammation, metabolism, intercellular communication, and gut microbiota have been linked to sarcopenia. Findings from these initial studies hold promise to inform geroscience-based research in the field of sarcopenia by offering a plausible biological framework for developing gerotherapeutics and monitoring their effects., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Sarcopenia is characterized by the progressive loss of skeletal muscle mass, strength, and function, significantly impacting overall health and quality of life in older adults. This narrative review explores emerging targets and potential treatments for sarcopenia, aiming to provide a comprehensive overview of current and prospective interventions., Methods: The review synthesizes current literature on sarcopenia treatment, focusing on recent advancements in muscle regeneration, mitochondrial function, nutritional strategies, and the muscle-microbiome axis. Additionally, pharmacological and lifestyle interventions targeting anabolic resistance and neuromuscular junction integrity are discussed., Results: Resistance training and adequate protein intake remain the cornerstone of sarcopenia management. Emerging strategies include targeting muscle regeneration through myosatellite cell activation, signaling pathways, and chronic inflammation control. Gene editing, stem cell therapy, and microRNA modulation show promise in enhancing muscle repair. Addressing mitochondrial dysfunction through interventions aimed at improving biogenesis, ATP production, and reducing oxidative stress is also highlighted. Nutritional strategies such as leucine supplementation and anti-inflammatory nutrients, along with dietary modifications and probiotics targeting the muscle-microbiome interplay, are discussed as potential treatment options. Hydration and muscle-water balance are emphasized as critical in maintaining muscle health in older adults., Conclusions: A combination of resistance training, nutrition, and emerging therapeutic interventions holds potential to significantly improve muscle function and overall health in the aging population. This review provides a detailed exploration of both established and novel approaches for the prevention and management of sarcopenia, highlighting the need for further research to optimize these strategies.

Background: An age-dependent normative values of calf circumference (CC) has been recently proposed as an accessible proxy for muscle mass. However, its usefulness to estimate sarcopenia has not been assessed. The objectives of the present study were to determine if the substitution of the classical way to assess muscle mass by these values have enough diagnostic accuracy and prognostic value among older adults living in the community., Methods: Data from the Toledo Study of Healthy Ageing (TSHA) were used. CC was measured using an anthropometric tape. We used two age-groups CC cut-off points: the TSHA CC median and the one proposed in the Longevity Check-up 7+ (Lookup 7+) project. Sarcopenia was defined based on the European Working Group on Sarcopenia in Older People (EWGSOP2), the Foundation for the National Institutes of Health (FNIH), and FNIH criteria standardized for our population (sFNIH). Frailty (according to the Frailty Phenotype and the Frailty Trait Scale-5) and disability (Katz index) were assessed at baseline and follow-up. Mortality and first hospitalization were also recorded. Logistic (incident frailty and worsening disability) and Cox (mortality and hospitalization) regressions were performed. Diagnostic accuracy was assessed through Kappa index, AUCs, positive and negative predictive values. Predictive ability was assessed through AUCs and integrated AUCs (IAUCs)., Results: 1531 participants (74.8 ± 5.8 years; 45.6% men) were included in the analysis. Prevalence rates of sarcopenia were 22.7% (sFNIH), 15.0% (FNIH), and 13.9% (EWGSOP2). Using TSHA-based cut-points of CC, the prevalence of sarcopenia was 16.8% (sFNIH), 11.0% (FNIH), and 11.5% (EWGSOP2). According to LC7+-based CC cut-off points, sarcopenia prevalence was 17.6% (sFNIH), 11.9% (FNIH), and 12.4% (EWGSOP2). CC cut-off points showed low-to-moderate agreement (Kappa Index values between 0.49 and 0.69) with appendicular lean mass for the evaluation of sarcopenia. Sarcopenia identified by Lookup 7+ and TSHA CC cut-off points was associated with the adverse events examined, with similar AUCs and IAUCs than original sarcopenia definitions, and were lost after adjustment by baseline frailty, except when the original EWGSOP2 definition was used., Conclusions: Using normalized values of CC as a criteria of muscle mass shows moderate agreement with classical criteria for diagnosing sarcopenia and offer similar predictive value in community-dwelling older adults., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Individuals with Down syndrome (DS) experience premature aging. Whether accelerated aging involves changes in body composition parameters and is associated with early development of sarcopenia is unclear., Aims: To compare parameters of body composition and the prevalence of sarcopenia between adults with DS and the general population., Methods: Body composition was assessed by whole-body dual-energy X-ray absorptiometry (DXA). Fat mass (FMI) and skeletal mass indices (SMI) were calculated as the ratio between total body fat mass and appendicular lean mass and the square of height, respectively. Fat mass distribution was assessed by the android/gynoid fat ratio (A/G). Sarcopenia was defined according to the criteria and cut-points recommended by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). Data on age- and sex-matched non-DS controls were retrieved from the 2001-2002 National Health and Nutrition Examination Survey (NHANES) population., Results: Sixty-four DS adults (mean age 37.2 ± 12.0 years, 20.3% women) were enrolled and compared with age- and sex-matched NHANES participants (n = 256), in a 1:4 ratio. FMI (7.96 ± 3.18 kg/m 2 vs. 8.92 ± 4.83 kg/m 2 , p = 0.135), SMI (7.38 ± 1.01 kg/m 2 vs. 7.46 ± 2.77 kg/m 2 , p = 0.825) and A/G (0.98 ± 0.17 vs. 1.01 ± 0.22, p = 0.115) were not significantly different between DS and control participants. When the sample was stratified by sex, women with DS had a higher FMI compared with their NHANES controls (10.16 ± 4.35 kg/m 2 vs. 8.11 ± 4.29 kg/m 2 , p < 0.001), while men with DS had lower A/G ratio (1.04 ± 0.16 vs. 1.11 ± 0.22, p = 0.002). Sarcopenia was more frequent in individuals with DS than in controls (35.6% vs. 19.9%, p = 0.007). This association was stronger in men 40 years and older., Conclusions: Adults with DS have a higher prevalence of sarcopenia compared with the general population. This finding suggests that DS is associated with early muscle aging and calls for the design of interventions targeting the skeletal muscle to prevent or treat sarcopenia., (© 2024. The Author(s).)

Sarcopenia has a complex pathophysiology that encompasses metabolic dysregulation and muscle ultrastructural changes. Among the drivers of intracellular and ultrastructural changes of muscle fibers in sarcopenia, mitochondria and their quality control pathways play relevant roles. Mononucleated muscle stem cells/satellite cells (MSCs) have been attributed a critical role in muscle repair after an injury. The involvement of mitochondria in supporting MSC-directed muscle repair is unclear. There is evidence that a reduction in mitochondrial biogenesis blunts muscle repair, thus indicating that the delivery of functional mitochondria to injured muscles can be harnessed to limit muscle fibrosis and enhance restoration of muscle function. Injection of autologous respiration-competent mitochondria from uninjured sites to damaged tissue has been shown to reduce infarct size and enhance cell survival in preclinical models of ischemia-reperfusion. Furthermore, the incorporation of donor mitochondria into MSCs enhances lung and cardiac tissue repair. This strategy has also been tested for regeneration purposes in traumatic muscle injuries. Indeed, the systemic delivery of mitochondria promotes muscle regeneration and restores muscle mass and function while reducing fibrosis during recovery after an injury. In this review, we discuss the contribution of altered MSC function to sarcopenia and illustrate the prospect of harnessing mitochondrial delivery and restoration of MSCs as a therapeutic strategy against age-related sarcopenia.

Sarcopenia, the age-associated decline in skeletal muscle mass and strength, is a condition with a complex pathophysiology. Among the factors underlying the development of sarcopenia are the progressive demise of motor neurons, the transition from fast to slow myosin isoform (type II to type I fiber switch), and the decrease in satellite cell number and function. Mitochondrial dysfunction has been indicated as a key contributor to skeletal myocyte decline and loss of physical performance with aging. Several systems have been implicated in the regulation of muscle plasticity and trophism such as the fine-tuned and complex regulation between the stimulator of protein synthesis, mechanistic target of rapamycin (mTOR), and the inhibitor of mTOR, AMP-activated protein kinase (AMPK), that promotes muscle catabolism. Here, we provide an overview of the molecular mechanisms linking mitochondrial signaling and quality with muscle homeostasis and performance and discuss the main pathways elicited by their imbalance during age-related muscle wasting. We also discuss lifestyle interventions (i.e., physical exercise and nutrition) that may be exploited to preserve mitochondrial function in the aged muscle. Finally, we illustrate the emerging possibility of rescuing muscle tissue homeostasis through mitochondrial transplantation.

Background: Wide consensus exists on the notion that low muscle mass is a predictor of negative health-related events, such as disability, morbidity, and mortality. Indeed, the European Working Group on Sarcopenia in Older People 2 had identified muscle mass as the key component to confirm the diagnosis of sarcopenia. However, the lack of normative values for muscle mass across ages hampers the practical assessment of this important parameter. The aim of the present study was to produce cross-sectional centile and normative values for calf circumference (a surrogate estimation of muscle mass) across a wide spectrum of ages using a large and unselected sample of community-dwellers enrolled in the Longevity Check-up 7+ (Lookup 7+) project., Methods: This is a cross-sectional study using the data of Lookup 7+ project, an ongoing study started in June 2015 and conducted in unconventional settings (i.e., exhibitions, malls, and health promotion campaigns). Candidate participants were considered eligible for enrolment if they were at least 45 years of age and provided written informed consent. Calf circumference was measured using an inextensible but flexible plastic tape in a sitting position with the knee and ankle at a right angle and the feet resting on the floor. Normative values for calf circumference from ages 45 to 80 + years were generated., Results: A total of 11 814 participants were enrolled from 1 June 2015 to 30 September 2022. The mean age of participants included in the analyses was 61.8 years (standard deviation; 10.2 years; range: 45-98 years), and 6686 (57%) were women. Normative values for calf circumference were obtained for men and women, stratified by age groups. Accordingly, a calf circumference tape, with colour bands that demarcate the centiles range into which the patient falls, was created and validated., Conclusions: Our study established age- and gender-specific centile reference values for calf circumference. The calf circumference tape can be used to easily interpret the assessment in every-day practice for the early detection of individuals with or at risk of sarcopenia and malnutrition., (© 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.)

Sarcopenia is a geriatric condition characterized by a progressive loss of skeletal muscle mass and strength, with an increased risk of adverse health outcomes (e.g., falls, disability, institutionalization, reduced quality of life, mortality). Pharmacological remedies are currently unavailable for preventing the development of sarcopenia, halting its progression, or impeding its negative health outcomes. The most effective strategies to contrast sarcopenia rely on the adoption of healthier lifestyle behaviors, including adherence to high-quality diets and regular physical activity. In this review, the role of nutrition in the prevention and management of sarcopenia is summarized. Special attention is given to current "blockbuster" dietary regimes and agents used to counteract age-related muscle wasting, together with their putative mechanisms of action. Issues related to the design and implementation of effective nutritional strategies are discussed, with a focus on unanswered questions on the most appropriate timing of nutritional interventions to preserve muscle health and function into old age. A brief description is also provided on new technologies that can facilitate the development and implementation of personalized nutrition plans to contrast sarcopenia., Competing Interests: Declaration of competing interest Declarations of interest: E.M. has received personal fees from Abbott, Difass International, Nestlé, and Pfizer., (Copyright © 2023. Published by Elsevier Inc.)

The maintenance of functional health is pivotal for achieving independent life in older age. The aged muscle is characterized by ultrastructural changes, including loss of type I and type II myofibers and a greater proportion of cytochrome c oxidase deficient and succinate dehydrogenase positive fibers. Both intrinsic (e.g., altered proteostasis, DNA damage, and mitochondrial dysfunction) and extrinsic factors (e.g., denervation, altered metabolic regulation, declines in satellite cells, and inflammation) contribute to muscle aging. Being a hub for several cellular activities, mitochondria are key to myocyte viability and mitochondrial dysfunction has been implicated in age-associated physical decline. The maintenance of functional organelles via mitochondrial quality control (MQC) processes is, therefore, crucial to skeletal myofiber viability and organismal health. The autophagy-lysosome pathway has emerged as a critical step of MQC in muscle by disposing organelles and proteins via their tagging for autophagosome incorporation and delivery to the lysosome for clearance. This pathway was found to be altered in muscle of physically inactive older adults. A relationship between this pathway and muscle tissue composition of the lower extremities as well as physical performance was also identified. Therefore, integrating muscle structure and myocyte quality control measures in the evaluation of muscle health may be a promising strategy for devising interventions fostering muscle health., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Previous studies found a lower prevalence of sarcopenia in older adults engaged in regular aerobic training (AT) or with greater adherence to a Mediterranean (MED) diet. However, the effect of their combination on sarcopenia indices is unknown. The present study tested the association between AT plus a MED diet and the presence of sarcopenia and its defining elements in a sample of Italian older adults enrolled in the Longevity Check-up 7+ (Lookup 7+) project. Analyses were conducted in participants 65+ years, with a body mass index of at least 18.5 kg/m 2 , engaged in regular AT, and without missing information for the variables of interest. MED diet adherence was evaluated via a modified version of the MEDI-LITE score and categorized as low, moderate, or high. The presence of sarcopenia was established by handgrip strength and appendicular skeletal muscle mass (ASM) values below sex-specific cut-points recommended by the European Working Group on Sarcopenia in Older People 2. Data from 491 older adults were analyzed for the present study. The mean age was 72.7 ± 5.7 years, and 185 (37.7%) were women. MED diet adherence was low in 59 (12.0%) participants, moderate in 283 (57.6%), and high in 149 (30.3%). Sarcopenia was identified in 26 participants (5.3%), with no differences across MED diet adherence groups. The results of binary logistic regression showed no significant associations between AT plus adherence to a MED diet and dynapenia, low ASM, or sarcopenia. The findings of the present study indicate that the combination of AT with a MED diet is not associated with a lower probability of sarcopenia or its defining elements in Italian older adults enrolled in Lookup 7+. Further research is warranted to establish whether exercise frequency, volume, intensity, and length of engagement in AT impact the association between MED diet and sarcopenia.

Declines in physical performance and cognition are commonly observed in older adults. The geroscience paradigm posits that a set of processes and pathways shared among age-associated conditions may also serve as a molecular explanation for the complex pathophysiology of physical frailty, sarcopenia, and cognitive decline. Mitochondrial dysfunction, inflammation, metabolic alterations, declines in cellular stemness, and altered intracellular signaling have been observed in muscle aging. Neurological factors have also been included among the determinants of sarcopenia. Neuromuscular junctions (NMJs) are synapses bridging nervous and skeletal muscle systems with a relevant role in age-related musculoskeletal derangement. Patterns of circulating metabolic and neurotrophic factors have been associated with physical frailty and sarcopenia. These factors are mostly related to disarrangements in protein-to-energy conversion as well as reduced calorie and protein intake to sustain muscle mass. A link between sarcopenia and cognitive decline in older adults has also been described with a possible role for muscle-derived mediators (i.e., myokines) in mediating muscle-brain crosstalk. Herein, we discuss the main molecular mechanisms and factors involved in the muscle-brain axis and their possible implication in cognitive decline in older adults. An overview of current behavioral strategies that allegedly act on the muscle-brain axis is also provided.

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.)

Muscle strength is a relevant metric of aging. Greater adherence to Mediterranean diet is associated with better health outcomes across all life stages; however, evidence on the relationship between Mediterranean diet and muscle strength in older adults is inconclusive. In this study, we evaluated the relationship between adherence to Mediterranean diet and handgrip strength in a large sample of community-dwelling older adults from the Longevity Check-up 7+ project. A total of 2963 participants (mean age 72.8 ± 5.7 years; 54.4% women) were analyzed. Mediterranean diet adherence was evaluated using a modified Medi-Lite score and categorized as low (≤8), good (9 to 11), or high (≥12). Handgrip strength was categorized as normal or low according to cut-points by the European Working Group on Sarcopenia in Older People 2. Older adults with lower Mediterranean diet adherence had a significantly higher prevalence of probable sarcopenia (25.9%) than those with good (19.1%) or high (15.5%) adherence. The proportion of participants with probable sarcopenia increased with age, but it remained lower in the good and high adherence groups. Logistic regression showed that greater Mediterranean diet adherence was associated with a lower risk of probable sarcopenia. Older age, female sex, and physical inactivity were associated with a greater risk of probable sarcopenia. Our findings emphasize the positive association between healthy lifestyles, including adherence to Mediterranean diet, and physical function in old age.

Multisystem derangements encompassing musculoskeletal, stress, and metabolic response have been described in older adults with physical frailty and sarcopenia (PF&S). Whether PF&S is also associated with markers of cellular senescence has yet to be explored. To address this research question, we quantified the serum levels of selected inflammatory, mitochondrial, and senescence-associated secretory phenotype (SASP)-related factors in 22 older adults with PF&S (mean age 75.5 ± 4.7 years; 81.8% women) and 27 nonPF&S controls (mean age 75.0 ± 4.4 years; 62.9% women) and evaluated their association with PF&S. Markers of inflammation (interleukin (IL)1- β , IL6, and tumor necrosis factor α (TNF-α)), matrix remodeling (Serpin E1, intercellular adhesion molecule 1 (ICAM-1), and tissue inhibitor of metalloproteinases 1 (TIMP-1)), mitochondrial dysfunction (growth/differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21)), Activin A, and glial fibrillary acidic protein (GFAP) were assayed. Serum levels of TNF-α and those of the SASP-related factors ICAM-1 and TIMP-1 were found to be higher, while IL1- β and IL6 were lower in PF&S participants compared with controls. Partial least squares discriminant analysis allowed discrimination of PF&S from nonPF&S participants with 74.0 ± 3.4% accuracy. Markers that significantly contributed to the classification were ICAM-1, TIMP-1, TNF-α, GFAP, and IL6. Future studies are warranted to establish whether inflammatory and SASP-related pathways are causally linked to the development and progression of PF&S, and may represent new targets for interventions.

The mammalian target of rapamycin (mTOR) is a major regulator of skeletal myocyte viability. The signaling pathways triggered by mTOR vary according to the type of endogenous and exogenous factors (e.g., redox balance, nutrient availability, physical activity) as well as organismal age. Here, we provide an overview of mTOR signaling in skeletal muscle, with a special focus on the role played by mTOR in the development of sarcopenia. Intervention strategies targeting mTOR in sarcopenia (e.g., supplementation of plant extracts, hormones, inorganic ions, calorie restriction, and exercise) have also been discussed.

The present study examined the association between lower-limb muscle power and protein-related parameters in older adults. This study followed a cross-sectional design. Participants were community-dwelling older adults. Candidates were considered eligible if they were 60 years or older, lived independently, and possessed sufficient physical and cognitive abilities to perform all the measurements required by the protocol. The 5 times sit-to-stand (5STS) test was performed as fast as possible according to a standard protocol. Absolute, relative, and allometric muscle power measures were estimated using 5STS-based equations. Diet was assessed by 24-h dietary recall and diet composition was estimated using a nutritional software. One-hundred and ninety-seven older adults participated to the present study. After adjustment for covariates, absolute and allometric muscle power were negatively associated with body weight-adjusted protein intake. Our findings indicate that absolute and allometric muscle power estimated through a simple equation are negatively associated with body weight-adjusted protein intake in community-dwelling older adults.

Objective: Low muscle mass is one of the mediators of numerous complications accompanying malnutrition status and sarcopenia and at the same time may have a greater effect on survival than other clinical characteristics. In this study, we evaluated the impact of low appendicular skeletal muscle (ASM) on all-cause 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 of the Sirente geographic area (L'Aquila, Italy) (n = 364). Participants were categorised in low or normal ASM based on the COONUT equation that considered calf circumference, age and gender., Primary Outcome: All-cause mortality over 10 years according to the low ASM estimated by calf circumference., Results: Low estimated ASM was identified in 128 participants (37 %). A total of 245 deaths were recorded over 10 years: 110 among participants with low ASM (85.3 %) and 135 among persons with normal ASM (65.1 %; p < 0.001). Participants with low ASM had a higher risk of death than those with normal ASM (HR: 3.38; 95 % CI: 1.93-5.93). This association remained statistically significant after adjusting for a number of potential confounders, such as age, gender, ADL impairment, cognitive impairment, BMI, and plasma CRP and IL6 levels (HR: 1.84; 95 % CI: 1.03-3.28)., Conclusions: Our findings show that low estimated ASM by calf circumference is predictive of 10 years mortality in older community-dwellers. The derived equation used in the present study to estimate ASM, based on calf circumference, may be particularly relevant in clinical practice. Hence, in older persons with low ASM, interventions targeting muscle mass may be effective at preventing or postponing negative health outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Sarcopenia is an age-related neuromuscular disease characterized by substantial muscle atrophy, dynapenia and/or loss of physical function. Sarcopenia progression increases the risk for numerous negative events, including falls, disability, hospitalization, nursing home placement, and death. As such, this condition is recognized as an important topic in gerontology and geriatrics. The best approach to counteract the development and progression of sarcopenia is actively debated. Resistance training (RT) has received special attention in this context, owing to the large number of studies showing its ability to produce significant improvements in sarcopenia-related parameters. Recommendations to guide RT prescription for older adults with different conditions, including people who have traits of sarcopenia, have been published. Some authors have argued that RT guidelines for older adults are similar to one another, which may indicate that the presence of sarcopenia does not require specific physical exercise programs. However, older people with sarcopenia might present with peculiar physical, biomechanical, physiological, and psychosocial characteristics that, in our view, are not taken into adequate consideration in existing exercise guidelines. Here, we present evidence to support the view that RT prescription for older adults with sarcopenia is complex, multifactorial, and still needs more evidence., Competing Interests: Conflict of interest The authors have no conflict of interest to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Severe clinical pictures and sequelae of COVID-19 disease are immune mediated and characterized by a 'cytokine storm'. Skeletal muscle has emerged as a potent regulator of immune system function. The aim of the present study is to define the prevalence of sarcopenia among COVID-19 survivors and the negative impact of sarcopenia on the post-acute COVID-19 syndrome and its related risk factors., Methods: A total of 541 subjects recovered from COVID-19 disease were enrolled in the Gemelli Against COVID-19 Post-Acute Care between April 2020 and February 2021. They underwent a multidisciplinary clinical evaluation and muscle strength and physical performance assessment., Results: Mean age was 53.1 years (SD 15.2, range from 18 to 86 years), and 274 (51%) were women. The prevalence of sarcopenia was 19.5%, and it was higher in patients with a longer hospital stay and lower in patients who were more physically active and had higher levels of serum albumin. Patients with sarcopenia had a higher number of persistent symptoms than non-sarcopenic patients (3.8 ± 2.9 vs. 3.2 ± 2.8, respectively; P = 0.06), in particular fatigue, dyspnoea, and joint pain., Conclusions: Sarcopenia identified according to the EWGSOP2 criteria is high in patients recovered from COVID-19 acute illness, particularly in those who had experienced the worst clinical picture reporting the persistence of fatigue and dyspnoea. Our data suggest that sarcopenia, through the persistence of inflammation, could be the biological substrate of long COVID-19 syndrome. Physical activity, especially if associated with adequate nutrition, seems to be an important protective factor., (© 2022 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: The present systematic review and meta-analysis investigated the cross-sectional and longitudinal associations between protein intake and sarcopenia in older adults., Methods: Observational studies that investigated the association between protein intake and sarcopenia as the primary or secondary outcome in people aged 60 years and older were included. Studies published in languages other than English, Italian, Portuguese, and Spanish were excluded. Studies were retrieved from MEDLINE, SCOPUS, EMBASE, CINAHL, AgeLine, and Food Science Source databases through January 31, 2022. A pooled effect size was calculated based on standard mean differences., Results: Five cross-sectional studies, one longitudinal study, and one case-control study that investigated 3353 community-dwelling older adults with a mean age of approximately 73 years were included. The meta-analysis of four studies indicated that older adults with sarcopenia consumed significantly less protein than their peers with no sarcopenia., Conclusions: Results of the present study suggest that an inadequate protein intake might be associated with sarcopenia in older adults.

Background: Sarcopenia is associated with adverse outcomes in older people. Several tools are recommended to assess muscle mass, muscle strength and physical performance, but are not always available in daily practice., Objective: The aim of the present study is to evaluate if there is a correlation between the personal perception of physical performance (assessed through a question on personal functional status) and the effective presence of sarcopenia (according to the EWGSOP2 definition) using data from the Longevity Check-up 7 + project., Design: Cross-sectional study., Setting: The Longevity Check-up 7 + project is an ongoing study started in June 2015 and conducted in unconventional settings (i.e., exhibitions, malls, and health promotion campaigns)., Subjects: Candidate participants are eligible for enrollment if they are at least 18 years of age and provide written informed consent. For the present study subjects 65 years age old and older have been considered (n = 2901)., Methods: According to the most recent EWGSOP2 consensus definition, subjects were defined to be affected by probable sarcopenia when handgrip strength was less than 27 kg in male and less than 16 kg in female, respectively. Furthermore, a single question assessed the perceived health status regarding own physical performance: "Do you have any difficulty in walking 400 m?"., Results: Using the EWGSOP2 algorithm, 529 (18,9%) participants were identified as affected by probable sarcopenia with a significant higher prevalence among subjects with self-reported difficulty in walking 400 m compared to participant without any difficulty (33.6% versus 13.1%, respectively; p < 0.001). Relative to participants without self-reported difficulty, those subjects with self-reported difficulty in walking 400 m showed a significantly higher risk of sarcopenia (odds ratio [OR]: 3.34; 95% confidence interval [CI]: 2.75-4.07)., Conclusions: A single "Red Flag" question such as "Do you have any difficulty in walking 400 m?" should be considered as a recommended method for screening probable sarcopenia risk., (© 2022. The Author(s).)

Purpose of Review: Multisystem derangements, encompassing metabolic, musculoskeletal and stress-response systems, occur during aging and are associated with the development of physical frailty and sarcopenia. These modular changes are relevant sources for the identification of biomarkers for the two conditions. Here, we provide an up-to-date overview on existing biomarkers of physical frailty and sarcopenia and discuss emerging approaches for biomarker discovery., Recent Findings: Inflammatory, metabolic and hematologic markers are shared between physical frailty and sarcopenia. Gut microbial derivatives and damage-associated molecular patterns transferred via extracellular vesicles have been indicated as possible gut-muscle axis regulators and candidate markers of physical frailty and sarcopenia., Summary: Mediators of metabolic, musculoskeletal and stress-response system dysregulation are shared by physical frailty and sarcopenia and indicate the existence of common pathophysiological pathways. Multiplatform biomarker analyses have been proposed as an innovating approach for tracking the multifaceted and dynamic nature of physical frailty and sarcopenia. Upon validation, the identified biomarkers may support diagnostic makeup and tracking of the two conditions in both research and clinical settings., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The dynamic nature of sarcopenia, including possible transitions between its different stages, is currently unknown. We aimed to explore 12 year transitions through sarcopenia stages and identify factors associated with different sarcopenia trajectories in older adults., Methods: We included 3219 participants (aged ≥60 years, 35.8% men, 96.4% community-dwelling) from the SNAC-K study. No sarcopenia (normal muscle strength and mass), probable sarcopenia (low muscle strength and normal muscle mass), and sarcopenia (low muscle strength and mass) were assessed at baseline and up to 12 years. Such conditions were defined based on a modified version of the EWGSOP2 criteria with muscle strength evaluated through handgrip or chair stand tests, and muscle mass from calf circumference. We estimated 1, 5, and 10 year transition probabilities through continuous-time multistage Markov modelling. Sociodemographic, lifestyle, and medical factors associated with the likelihood of different transitions were evaluated with proportional intensity models, and the associations' strength was expressed as hazard ratio (HR) and 95% confidence interval (CI)., Results: Participants with no sarcopenia had 10-year probabilities of 17.1% and 5.1% to develop probable sarcopenia and sarcopenia, and a 40.4% chance of not transitioning. Those with probable sarcopenia had similar 5-year chances of developing sarcopenia (10.3%) and reverting to no sarcopenia (10.7%). Participants with sarcopenia had chances to revert to probable sarcopenia ranging from 8.2% (at 5 years) to 4.7% (at 10 years), and a 70.9% chance of dying after 10 years. Older age (HR = 1.11, 95% CI: 1.07-1.14), male sex (HR = 1.84, 95% CI: 1.16-2.91), current smoking (HR = 1.84, 95% CI: 1.16-2.91), and higher number of chronic diseases (HR = 1.07, 95% CI: 1.00-1.14) were associated with sarcopenia development, while higher levels of physical activity (HR = 1.84, 95% CI: 1.19-2.84) and cognitive function (HR = 1.17, 95% CI: 1.05-1.31 per each 1-point increase in the Mini-Mental State Examination) were associated with subsequent higher reversion rates from probable sarcopenia to no sarcopenia (P < 0.05 for all). None of the explored characteristics were associated with sarcopenia reversion to healthier stages., Conclusions: Sarcopenia appears to be a dynamic condition with possible two-way transitions between different sarcopenia stages, especially the earliest ones. Timely interventions to improve physical and cognitive function and better control individuals' chronic conditions could help counteract sarcopenia progression., (© 2021 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: Physical frailty and sarcopenia show extensive clinical similarities. Whether biomarkers exist that are shared by the two conditions is presently unclear., Methods: We conducted a systematic review and meta-analysis of cross-sectional and longitudinal studies that investigated the association of frailty and/or sarcopenia with biomarkers as a primary or secondary outcome in adults aged 60 years and older. Only studies published in English that defined frailty using a validated scale and/or questionnaire and diagnosed sarcopenia according to the presence of muscle atrophy plus dynapenia or low physical function were included. Studies were identified from a systematic search of MEDLINE and SCOPUS databases from inception through August 2020. The quality of reporting of each study was assessed by using the Quality Assessment Tool for Observational Cohort, Cross-Sectional and Case-Control studies of the National Institute of Health. A meta-analysis was conducted when at least three studies investigated the same biomarker in both frailty and sarcopenia. Pooled effect size was calculated based on standard mean differences and random-effect models. Sensitivity analysis was performed based on age and the setting where the study was conducted., Results: Eighty studies (58 on frailty and 22 on sarcopenia) met the inclusion criteria and were included in the qualitative analysis. Studies on frailty included 33,160 community-dwellers, hospitalized, or institutionalized older adults (60-88 years) from 21 countries. Studies on sarcopenia involved 4904 community-living and institutionalized older adults (68-87.6 years) from 9 countries. Several metabolic, inflammatory, and hematologic markers were found to be shared between the two conditions. Albumin and hemoglobin were negatively associated with both frailty and sarcopenia. Interleukin 6 was associated with frailty and sarcopenia only in people aged < 75. Community-dwelling older adults with frailty and sarcopenia had higher levels of tumor necrosis factor alpha compared with their robust and non-sarcopenic counterparts., Conclusions: A set of metabolic, hematologic, and inflammatory biomarkers was found to be shared by frailty and sarcopenia. These findings fill a knowledge gap in the quest of biomarkers for these conditions and provide a rationale for biomarker selection in studies on frailty and sarcopenia., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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.)

Background & Aim: Sarcopenia is frequent in cirrhosis and is associated with unfavourable outcomes. The role of the gut-liver-muscle axis in this setting has been poorly investigated. The aim of this study was to identify gut microbiota, metabolic and inflammatory signatures associated with sarcopenia in cirrhotic patients., Methods: Fifty cirrhotic patients assessed for the presence of sarcopenia by the quantification of muscle mass and strength were compared with age- and sex-matched controls. A multiomic analysis, including gut microbiota composition and metabolomics, serum myokines and systemic and intestinal inflammatory mediators, was performed., Results: The gut microbiota of sarcopenic cirrhotic patients was poor in bacteria associated with physical function (Methanobrevibacter, Prevotella and Akkermansia), and was enriched in Eggerthella, a gut microbial marker of frailty. The abundance of potentially pathogenic bacteria, such as Klebsiella, was also increased, to the detriment of autochthonous ones. Sarcopenia was associated with elevated serum levels of pro-inflammatory mediators and of fibroblast growth factor 21 (FGF21) in cirrhotic patients. Gut microbiota metabolic pathways involved in amino acid, protein and branched-chain amino acid metabolism were up-regulated, in addition to ethanol, trimethylamine and dimethylamine production. Correlation networks and clusters of variables associated with sarcopenia were identified, including one centred on Klebsiella/ethanol/FGF21/Eggerthella/Prevotella., Conclusions: Alterations in the gut-liver-muscle axis are associated with sarcopenia in patients with cirrhosis. Detrimental but also compensatory functions are involved in this complex network., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

During aging and menopausal transition in women, a progressive muscle degeneration ( i.e. decrease in quality and muscle function) occurs. This muscle dysfunction, caused by decreased proliferation of muscle satellite cells, increased levels of inflammatory markers, and altered levels of sex hormones, exposes women to a raised incidence of sarcopenia. In this regard, hormonal balance and, in particular, estradiol, seems to be essential in skeletal muscle function. The role of the estradiol on satellite cells and the release of inflammatory cytokines in menopausal women are reviewed. In particular, estradiol has a beneficial effect on the skeletal muscle by stimulating satellite cell proliferation. Skeletal muscle can respond to estrogenic hormonal control due to the presence of specific receptors for estradiol at the level of muscle fibers. Additionally, estradiol can limit inflammatory stress damage on skeletal muscle. In this review, we primarily focused on the role of estradiol in sarcopenia and on the possibility of using Estradiol Replacement Therapy, which combined with nutritional and physical activity programs, can counteract this condition representing a valid tool to treat sarcopenia in women., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer BS declared a shared affiliation with some of the authors, RC and EM, to the handling editor at time of review., (Copyright © 2021 Geraci, Calvani, Ferri, Marzetti, Arosio and Cesari.)

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.

Background: The "Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies" (SPRINTT) project sponsored a multi-center randomized controlled trial (RCT) with the objective to determine the effect of physical activity and nutrition intervention for prevention of mobility disability in community-dwelling frail older Europeans. We describe here the design and feasibility of the SPRINTT nutrition intervention, including techniques used by nutrition interventionists to identify those at risk of malnutrition and to carry out the nutrition intervention., Methods: SPRINTT RCT recruited older adults (≥ 70 years) from 11 European countries. Eligible participants (n = 1517) had functional limitations measured with Short Physical Performance Battery (SPPB score 3-9) and low muscle mass as determined by DXA scans, but were able to walk 400 m without assistance within 15 min. Participants were followed up for up to 3 years. The nutrition intervention was carried out mainly by individual nutrition counseling. Nutrition goals included achieving a daily protein intake of 1.0-1.2 g/kg body weight, energy intake of 25-30 kcal/kg of body weight/day, and serum vitamin D concentration ≥ 75 mmol/L. Survey on the method strategies and feasibility of the nutrition intervention was sent to all nutrition interventionists of the 16 SPRINTT study sites., Results: Nutrition interventionists from all study sites responded to the survey. All responders found that the SPRINTT nutrition intervention was feasible for the target population, and it was well received by the majority. The identification of participants at nutritional risk was accomplished by combining information from interviews, questionnaires, clinical and laboratory data. Although the nutrition intervention was mainly carried out using individual nutritional counselling, other assisting methods were used as appropriate., Conclusion: The SPRINTT nutrition intervention was feasible and able to adapt flexibly to varying needs of this heterogeneous population. The procedures adopted to identify older adults at risk of malnutrition and to design the appropriate intervention may serve as a model to deliver nutrition intervention for community-dwelling older people with mobility limitations.

Sarcopenia, the age-related decline in muscle mass and strength/function, is a prototypical geroscience condition. The dissection of muscle-specific molecular pathways through analyses of tissue biopsies has provided valuable insights into the pathophysiology of sarcopenia. However, such an approach is unsuitable for capturing the dynamic nature of the condition. Furthermore, the muscle sampling procedure may be perceived as burdensome especially by multimorbid, frail older adults. To overcome these limitations, sophisticated statistical methods have been devised for the simultaneous analysis of circulating factors related to the multiple domains of sarcopenia. This approach has shown potential for achieving a more comprehensive appraisal of the condition, unveiling new therapeutic targets, and identifying meaningful biomarkers. Here, we discuss the main pathogenetic pathways of sarcopenia, with a focus on mediators that are currently in the spotlight as biomarkers and potential treatment targets., Competing Interests: Conflict of interest statement Nothing to declare., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Sarcopenia involves a progressive age-related decline of skeletal muscle mass and strength/function [...].

Detection of sarcopenia in primary care is a first and essential step in community-dwelling older adults before implementing preventive interventions against the onset of disabling conditions. In fact, leaving this condition undiagnosed and untreated can impact on the individual's quality of life and function, as well as on healthcare costs. This article summarizes the many instruments today available for promoting an earlier and prompter detection of sarcopenia in primary care, combining insights about its clinical management. Primary care physicians may indeed play a crucial role in the identification of individuals exposed to the risk of sarcopenia or already presenting this condition. To confirm the suspected diagnosis, several possible techniques may be advocated, but it is important that strategies are specifically calibrated to the needs, priorities and resources of the setting where the evaluation is conducted. To tackle sarcopenia, nutritional counselling and physical activity programs are today the two main interventions to be proposed. Multicomponent and personalized exercise programs can (and should) be prescribed by primary care physicians, taking advantage of validated programs ad hoc designed for this purpose (e.g., the Vivifrail protocol). It is possible that, in the next future, new pharmacological treatments may become available for tackling the skeletal muscle decline. These will probably find application in those individuals non-responding to lifestyle interventions., Competing Interests: Matteo Cesari received honoraria from Nestlé for presentations at scientific meetings and as member of scientific advisory boards. No other conflict of interest declared by the Authors.

Background: The European Working Group on Sarcopenia in Older People (EWGSOP2) recently updated the definition of sarcopenia in order to reflect scientific and clinical evidences., Objective: The aim is to explore the prevalence of sarcopenia (according to the new EWGSOP2 definition) and related risk factors among an unselected sample of subjects living in community., Setting and Participants: The Longevity Check-up 7+ project is an ongoing cross-sectional study started in June 2015 and conducted in unconventional settings (ie, exhibitions, malls, and health promotion campaigns). Candidate participants are eligible for enrollment if they are at least 18 years of age., Methods: Muscle strength was assessed by handgrip strength and physical performance was evaluated by chair stand test., Results: The mean age of 11,253 subjects was 55.6 (standard deviation 11.5, from 18 to 98 years) years, and 6356 (56%) were women. Using the EWGSOP2 algorithm, 973 participants (8.6%) were identified as affected by sarcopenia, and the prevalence of sarcopenia significantly increased with age. Sarcopenia was associated with diabetes prevalence ratio (PR) 1.42, 95% confidence interval (CI) 1.06-1.89, impairment in 400-m walking performance (PR 2.16, 95% CI 1.74-2.17), and self-reported unhealthy status (PR 1.77, 95% CI 1.45-2.17). Conversely, a decreased probability of being sarcopenic was detected among subjects following a healthy diet (PR 0.79, 95% CI 0.63-0.98) and involved in regular physical activity (PR 0.79, 95% CI 0.64-0.99)., Conclusions and Implications: Muscle strength and physical performance assessment should be considered as the recommended methods for the early detection of individuals at risk of probable sarcopenia., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

One of the most widely conserved hallmarks of aging is a decline in functional capabilities. Mobility loss is particularly burdensome due to its association with negative health outcomes, loss of independence and disability, and the heavy impact on quality of life. Recently, a new condition, physical frailty and sarcopenia, has been proposed to define a critical stage in the disabling cascade. Physical frailty and sarcopenia are characterized by weakness, slowness, and reduced muscle mass, yet with preserved ability to move independently. One of the strategies that have shown some benefits in combatting mobility loss and its consequences for older adults is physical activity. Here, we describe the opportunities and challenges for the development of physical activity interventions in people with physical frailty and sarcopenia. The aim of this article is to review age-related physio(patho)logical changes that impact mobility in old age and to provide recommendations and procedures in accordance with the available literature., Competing Interests: All of the authors of the present work are partners of the SPRINTT consortium, which is partially funded by the European Federation of Pharmaceutical Industries and Associations (EFPIA). The authors report no potential conflicts of interest in this work., (© 2020 Billot et al.)

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.

Skeletal muscle aging is associated with a significant loss of skeletal muscle strength and power (i.e., dynapenia), muscle mass and quality of life, a phenomenon known as sarcopenia. This condition affects nearly one-third of the older population and is one of the main factors leading to negative health outcomes in geriatric patients. Notwithstanding the exact mechanisms responsible for sarcopenia are not fully understood, mitochondria have emerged as one of the central regulators of sarcopenia. In fact, there is a wide consensus on the assumption that the loss of mitochondrial integrity in myocytes is the main factor leading to muscle degeneration. Mitochondria are also key players in senescence. It has been largely proven that the modulation of mitochondrial functions can induce the death of senescent cells and that removal of senescent cells improves musculoskeletal health, quality, and function. In this review, the crosstalk among mitochondria, cellular senescence, and sarcopenia will be discussed with the aim to elucidate the role that the musculoskeletal cellular senescence may play in the onset of sarcopenia through the mediation of mitochondria.

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.)

In the context of the management of the elderly patient with cancer, currently, a key topic may be expressed by sarcopenia. Sarcopenia in its various definitions and ambiguities in the older adult is always related to negative outcomes. A close correlation between sarcopenia and adverse outcomes such as treatment response or toxicity has also been shown in the patient with cancer. For these reasons, it becomes increasingly important to try to understand and therefore differentiate conditions such as the loss of muscle mass linked to normal aging, an independent pathological condition such as sarcopenia and finally a sometimes confusing pathologic condition called cachexia., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.

Purpose of Review: Given the role of leucine as a major regulator of muscle protein turnover, the consumption of protein sources enhanced with this essential amino acid, or its metabolite beta-hydroxy-beta-methylbutyrate (HMB), is assumed to give the greatest benefit in terms of maintenance of muscle mass and function during aging. The aim of this review is to discuss recent literature about HMB metabolism, its pharmacokinetics compared with the metabolite leucine, effectiveness of HMB to improve outcomes in older adults, and novel approaches for HMB use., Recent Findings: Overall, this review article highlights the potential relationship between HMB dietary supplementation and parameters related to maintenance of muscle mass and strength in older people. However, there are limitations in the studies conducted so far, including low number of participants per study group, heterogeneity of study designs, methodologies, and outcomes. The combination of HMB with other amino acids or supplements limits the ability to determine the direct impact of HMB alone., Summary: It is proposed that HMB may be utilized to protect or rebuild muscle mass in older people with reduced lean body mass.