Mitochondrial-derived vesicles in skeletal muscle remodeling and adaptation.

Mitochondrial remodeling is crucial to meet the bioenergetic demand to support muscle contractile activity during daily tasks and muscle regeneration following injury. A set of mitochondrial quality control (MQC) processes, including mitochondrial biogenesis, dynamics, and mitophagy, are in place to maintain a well-functioning mitochondrial network and support muscle regeneration. Alterations in any of these pathways compromises mitochondrial quality and may potentially lead to impaired myogenesis, defective muscle regeneration, and ultimately loss of muscle function. Among MQC processes, mitophagy has gained special attention for its implication in the clearance of dysfunctional mitochondria via crosstalk with the endo-lysosomal system, a major cell degradative route. Along this pathway, additional opportunities for mitochondrial disposal have been identified that may also signal at the systemic level. This communication occurs via inclusion of mitochondrial components within membranous shuttles named mitochondrial-derived vesicles (MDVs). Here, we discuss MDV generation and release as a mitophagy-complementing route for the maintenance of mitochondrial homeostasis in skeletal myocytes. We also illustrate the possible role of muscle-derived MDVs in immune signaling during muscle remodeling and adaptation.

Physical performance and negative events in very old adults: a longitudinal study examining the ilSIRENTE cohort.

BACKGROUND: Declining physical performance in old age is associated with a wide range of negative health-related outcomes. However, it is unclear which physical capabilities should be prioritized to obtain prognostic information in older adults. AIMS: To examine the associations between the performance on several physical function tests and falls, disability, and death in a well-characterized sample of very old Italian adults. METHODS: This was a prospective cohort study of older adults who lived in the mountain community of the Sirente geographic area in Central Italy. Physical performance was assessed using isometric handgrip strength (IHG), walking speed (WS) at a usual and fast pace, 5-time sit-to-stand test (5STS), and sit-to-stand power measures. Appendicular skeletal muscle mass was estimated from calf circumference using a validated equation. History of falls, incident falls, and disability status according to basic Activities of Daily Living (ADLs) were recorded over two years. Survival status was obtained from the participants' general practitioners and was confirmed by the National Death Registry over 10 years from enrolment. Linear, binary, and Cox regressions were performed to evaluate the association between physical performance measures and health outcomes. RESULTS: The mean age of the 255 participants was 84.2 ± 5.1 years, and 161 (63.1%) were women. Logistic regression indicated that IHG was significantly associated with incident ADL disability, whereas specific sit-to-stand muscle power was an independent predictor of death. No significant associations were observed between physical function and falls. CONCLUSIONS: Our findings indicate selective associations between physical function tests and the occurrence of negative events in very old adults, with poor IHG predicting disability and specific sit-to-stand muscle power being longitudinally associated with death.

Mitochondrial Quantity and Quality in 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.

Adherence to aerobic training combined with high protein intake is associated with low blood pressure in Italian older adults: a cross-sectional study.

BACKGROUND: Lifestyle habits have a key role in cardiometabolic health. The effects of combined aerobic training (AT) and high protein intake (HPI) on cardiometabolic parameters in older adults are not well established. AIMS: To investigate the association of AT and HPI with blood pressure (BP), blood glucose, and total blood cholesterol levels in a sample of Italian older adults enrolled in the Longevity Check-up 7 + (Lookup 7 +) study. METHODS: Lookup 7 + is an ongoing project started in June 2015 and conducted in unconventional settings (e.g., exhibitions, malls, health promotion campaigns) across Italy with the aim of fostering adoption of healthy lifestyles in the general population. For the present investigation, analyses were conducted in participants 65 + years and with body mass index values ≥ 18.5 kg/m2 (n = 3219). Systolic (SBP) and diastolic BP (DBP), blood glucose, and total blood cholesterol were measured. Protein intake was estimated using a 12-item food frequency questionnaire. HPI was operationalized as a daily protein intake ≥ 0.8 g/kg of body weight. AT was operationalized as the practice of running and/or swimming for 60 + minutes at least twice weekly during the previous year. RESULTS: The mean age of the 3219 participants was 72.7 ± 5.7 years, and 55.2% were women. Adherence to AT combined with a HPI was negatively and independently associated with SPB (ß: - 4.976; 95% confidence interval: - 9.8 to - 0.08). No other significant associations were observed. DISCUSSION AND CONCLUSIONS: Our results indicate that AT combined with HPI was negatively associated with SBP in a large and relatively unselected sample of Italian older adults living in the community. These findings need confirmation by ad hoc designed studies.

Mitochondrial-Derived Vesicles: The Good, the Bad, and the Ugly.

Mitophagy is crucial for maintaining mitochondrial quality. However, its assessment in vivo is challenging. The endosomal-lysosomal system is a more accessible pathway through which subtypes of extracellular vesicles (EVs), which also contain mitochondrial constituents, are released for disposal. The inclusion of mitochondrial components into EVs occurs in the setting of mild mitochondrial damage and during impairment of lysosomal function. By releasing mitochondrial-derived vesicles (MDVs), cells limit the unload of mitochondrial damage-associated molecular patterns with proinflammatory activity. Both positive and negative effects of EVs on recipient cells have been described. Whether this is due to the production of EVs other than those containing mitochondria, such as MDVs, holding specific biological functions is currently unknown. Evidence on the existence of different MDV subtypes has been produced. However, their characterization is not always pursued, which would be relevant to exploring the dynamics of mitochondrial quality control in health and disease. Furthermore, MDV classification may be instrumental in understanding their biological roles and promoting their implementation as biomarkers in clinical studies.

Effects of l-Arginine Plus Vitamin C Supplementation on l-Arginine Metabolism in Adults with Long COVID: Secondary Analysis of a Randomized Clinical Trial.

Altered l-arginine metabolism has been described in patients with COVID-19 and has been associated with immune and vascular dysfunction. In the present investigation, we determined the serum concentrations of l-arginine, citrulline, ornithine, monomethyl-l-arginine (MMA), and symmetric and asymmetric dimethylarginine (SDMA, ADMA) in adults with long COVID at baseline and after 28-days of l-arginine plus vitamin C or placebo supplementation enrolled in a randomized clinical trial, compared with a group of adults without previous history of SARS-CoV-2-infection. l-arginine-derived markers of nitric oxide (NO) bioavailability (i.e., l-arginine/ADMA, l-arginine/citrulline+ornithine, and l-arginine/ornithine) were also assayed. Partial least squares discriminant analysis (PLS-DA) models were built to characterize systemic l-arginine metabolism and assess the effects of the supplementation. PLS-DA allowed discrimination of participants with long COVID from healthy controls with 80.2 ± 3.0% accuracy. Lower markers of NO bioavailability were found in participants with long COVID. After 28 days of l-arginine plus vitamin C supplementation, serum l-arginine concentrations and l-arginine/ADMA increased significantly compared with placebo. This supplement may therefore be proposed as a remedy to increase NO bioavailability in people with long COVID.

Mammalian Target of Rapamycin (mTOR) Signaling at the Crossroad of Muscle Fiber Fate in Sarcopenia.

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.

Circulating Inflammatory, Mitochondrial Dysfunction, and Senescence-Related Markers in Older Adults with Physical Frailty and Sarcopenia: A BIOSPHERE Exploratory Study.

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-ß, 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-ß 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.

Associations between nutritional frailty and 8-year all-cause mortality in older adults: The Salus in Apulia Study.

INTRODUCTION: Preventive nutritional management of frailty, a multidimensional intermediate status in the ageing process, may reduce the risk of adverse health-related outcomes. We investigated the ability of a measure combining physical frailty with nutritional imbalance, defined as nutritional frailty, to predict all-cause mortality over a period of up to 8 years. METHODS: We analysed data on 1,943 older adults from the population-based 'Salus in Apulia Study'. Physical frailty was operationalized using Cardiovascular Health Study criteria and cognitive frailty by combining physical frailty with cognitive impairment. A novel five-item construct was built to assess the extent of nutritional imbalance identified with a machine learning algorithm. Cox models and Kaplan-Meier survival probability analyses of physical frailty, nutritional imbalance (two or more of the following: low body mass index, low skeletal muscle index, ≥2.3 g/day sodium intake, <3.35 g/day potassium intake and <9.9 g/day iron intake), cognitive frailty and the novel nutritional frailty phenotype (physical frailty plus nutritional imbalance) were applied to assess all-cause mortality risk, adjusted for age, sex, education and multimorbidity. RESULTS: The overall prevalence of nutritional frailty was 4.52% (95% confidence interval, CI:3.55-5.44), being more frequent in males. Subjects with nutritional frailty were at higher risk for all-cause mortality [hazard ratio (HR):2.31; 95%CI:1.41-3.79] than those with physical frailty (HR:1.45,95% CI:1.0-2.02), nutritional imbalance (HR:1.39; 95%CI:1.05-1.83) and cognitive frailty (HR:1.06; 95%CI:0.56-2.01). CONCLUSIONS: Efforts to identify, manage and prevent frailty should include the nutritional domain. The nutritional frailty phenotype may highlight major nutritional determinants that could drive survival and health trajectories in older adults.

Evidence-based recommendations for resistance and power training to prevent frailty in community-dwellers.

Frailty is a reversible state of reduced resilience to stressful events resulting from a multisystem impairment of the human body. As frailty progresses, people become more vulnerable to numerous adverse events, including falls and fractures, cognitive decline, disability, hospitalization, nursing home placement, and death. As such, substantial health care costs are associated with frailty. These features have led to the recognition of frailty as a public health problem. The identification of strategies for the management of frailty has, therefore, become a topic of extensive instigation. In this context, resistance (RT) and power training (PT) have received considerable attention, and experts in the field have recently suggested that both training modalities may improve frailty-related parameters. However, most studies have only included robust people and investigated frailty as a secondary outcome, so that current literature only allows RT and PT preventive programs against frailty to be designed. Here, we provide evidence-based critical recommendations for the prescription of RT and PT programs against incident frailty in community-dwellers.

Biomarkers of Physical Frailty and Sarcopenia: Coming up to the Place?

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 Aging: Insights from the Analysis of Extracellular Vesicles.

The progressive decline of cell function and integrity, manifesting clinically as increased vulnerability to adverse outcomes and death, is core to biological aging. Mitochondrial dysfunction, oxidative stress, altered intercellular communication (including chronic low-grade inflammation), genomic instability, telomere attrition, loss of proteostasis, altered nutrient sensing, epigenetic alterations, and stem cell exhaustion have been proposed as hallmarks of aging. These "aging pillars" are not mutually exclusive, making the matter intricate and leaving numerous unanswered questions. The characterization of circulating extracellular vesicles (EVs) has recently allowed specific secretory phenotypes associated with aging to be identified. As such, EVs may serve as novel biomarkers for capturing the complexity of aging. Besides the mitochondrial⁻lysosomal axis, EV trafficking has been proposed as an additional layer in mitochondrial quality control. Indeed, disruption of the mitochondrial⁻lysosomal axis coupled with abnormal EV secretion may play a role in the pathogenesis of aging and several disease conditions. Here, we discuss (1) the mechanisms of EV generation; (2) the relationship between the mitochondrial⁻lysosomal axis and EV trafficking in the setting of mitochondrial quality control; and (3) the prospect of using EVs as aging biomarkers and as delivery systems for therapeutics against age-related conditions.

Hypertension and functional capacities in community-dwelling older women: a cross-sectional study.

PURPOSE: The present study aimed to investigate the association between hypertension and physical/functional capacities in community-dwelling older females. MATERIALS AND METHODS: Older female volunteers were dichotomized in two groups: hypertensive (n = 134) and normotensive (n = 244). Volunteers had their medical records reviewed and underwent evaluations of anthropometric data (weight, height and body mass index) and of physical and functional capacities. RESULTS: The results showed that hypertensive older females presented higher values for age, weight, body mass index, and resting diastolic blood pressure than normotensive older females. Normotensive older females showed a higher performance in the one-leg stand test and six-minute walk test compared with hypertensive older females. Age, body mass index, maximal walking speed, performance in the Time Up and Go and six-minute walk test, and diagnosis of diabetes mellitus type II were factors associated with hypertension using the chi-square test. However, the multivariate regression analysis indicated that performance in the six-minute walk test was the only factor associated with hypertension. CONCLUSIONS: The patients with higher scores in the six-minute walk test, which is associated with aerobic capacity, show less odds to have clinical diagnosis of hypertension. However, hypertension was not associated with poor physical and functional capacity.

Inflammatory Mechanisms Associated with Skeletal Muscle Sequelae after Stroke: Role of Physical Exercise.

Inflammatory markers are increased systematically and locally (e.g., skeletal muscle) in stroke patients. Besides being associated with cardiovascular risk factors, proinflammatory cytokines seem to play a key role in muscle atrophy by regulating the pathways involved in this condition. As such, they may cause severe decrease in muscle strength and power, as well as impairment in cardiorespiratory fitness. On the other hand, physical exercise (PE) has been widely suggested as a powerful tool for treating stroke patients, since PE is able to regenerate, even if partially, physical and cognitive functions. However, the mechanisms underlying the beneficial effects of physical exercise in poststroke patients remain poorly understood. Thus, in this study we analyze the candidate mechanisms associated with muscle atrophy in stroke patients, as well as the modulatory effect of inflammation in this condition. Later, we suggest the two strongest anti-inflammatory candidate mechanisms, myokines and the cholinergic anti-inflammatory pathway, which may be activated by physical exercise and may contribute to a decrease in proinflammatory markers of poststroke patients.

Sex- and age-specific normative values of lower extremity muscle power in Italian community-dwellers.

BACKGROUND: Muscle power is associated with health-related parameters. Simple equations were validated to estimate lower extremity muscle power measures based on the time to complete the five-repetition sit-to-stand test. The present study was conducted to provide lower extremity muscle power estimates and produce centile values in a large and relatively unselected population across a wide age spectrum. METHODS: Data were from the Longevity Check-up 7+ (Lookup 7+) project, an ongoing initiative conducted in unconventional settings (e.g., exhibitions, shopping centres and health promotion campaigns) across Italy to foster adoption of healthy lifestyles. Absolute, relative, allometric and specific muscle power measures of the lower extremities were estimated using validated formulas. Cross-sectional centile and normative values for muscle power measures from 18 to 81+ years were produced for the two sexes. Smoothed normative curves for men and women were constructed using the lambda-mu-sigma method. RESULTS: From 1 June 2015 to 31 October 2021, 13 515 participants were enrolled of whom 12 864 were eligible for the present study. Mean age was 55.9 years (standard deviation: 14.8 years; range: 18-98 years), and 7217 (56.%) were women. Absolute, relative, allometric and specific muscle power declined significantly with age. Specific patterns of decline were observed according to sex and muscle power parameter. Absolute muscle power peaked at 41-50 and 31-40 years in men and women, respectively. Afterwards, a decline rate of approximately 12% per decade was observed, regardless of sex. Relative muscle power showed the largest reduction with age, such that it was 40.6% and 46.4% smaller in men and women older than 80, respectively, compared with those aged 18-30 years. Age-related changes in allometric and specific muscle power measures were similar between men and women. CONCLUSIONS: Data from the Lookup 7+ project indicate that lower extremity muscle power estimated using simple equations is significantly associated with age. Sex-specific patterns of decline in absolute and relative muscle power were observed with age. Allometric and specific muscle power declined at a similar rate in men and women.

Restoring Mitochondrial Function and Muscle Satellite Cell Signaling: Remedies against Age-Related Sarcopenia.

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.

Effects of resistance training associated with a verbal fluency task on physical performance and cognitive function in frail nursing home residents.

OBJECTIVES: Studies examining the effects of dual-task resistance training (RT) on nursing-home residents are still scarce. To add knowledge to this field, the present study compared the effects of 12-week RT and RT plus cognitive task (COG) programs on physical performance and cognitive function in a sample of frail nursing home residents. METHODS: This is an experimental study that combined data from two studies that examined older adults living in nursing home residences in Brazil. Exercise groups performed a 12-week RT protocol that included four exercises, with 3-4 times (sets) of 8-10 repetitions at 70 %-75 % of 1-repetition maximum (1RM), twice a week. The RT+COG group evoked as many words was possible for specific categories during concentric actions of the squat on the chair (until 90° knee flexion) and seated unilateral knee extension exercises. Global cognitive function and physical performance were evaluated using the Mini-Mental State Examination (MMSE) and Short Physical Performance Battery (SPPB) tests, respectively. RESULTS: After interventions, participants in the RT+COG and RT groups had significantly greater lower-limb muscle strength compared with the control group (CG). Those in the RT+COG group had greater tandem performance in comparison to RT and CG groups. CONCLUSIONS: Our findings indicate that RT preserves lower-limb muscle strength in frail nursing home residents, regardless of performance of cognitive tasks. Better balance was exclusively observed in the RT+COG, whereas significant improvements in mobility status were only found in the RT group. The present investigation was based on a small sample of nursing home residents. Larger and more structured studies are necessary to confirm our results.

A simple medical device development according to normative values of calf circumference across ages: results from the Italian Longevity Check-up 7+ (Lookup 7+) project.

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.

Diagnostic and prognostic value of calf circumference for sarcopenia in community-dwelling older adults.

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.

Predictive values of relative fat mass and body mass index on cardiovascular health in community-dwelling older adults: Results from the Longevity Check-up (Lookup) 7.

OBJECTIVES: To assess the predictive value of relative fat mass compared to body mass index for hypertension, diabetes, hyperlipidemia, and heightened cardiovascular risk in a cohort of community-dwelling older adults from the Longevity Check-up 7+ cohort. STUDY DESIGN: Retrospective cross-sectional study. MAIN OUTCOME MEASURES: Hyperlipidemia was defined as total cholesterol ≥200 mg/dL or ongoing lipid-lowering treatment. Diabetes was defined either as self-reported diagnosis or fasting blood glucose >126 mg/dL or a random blood glucose >200 mg/dL. Hypertension was defined as blood pressure ≥ 140/90 mmHg or requiring daily antihypertensive medications. Heightened cardiovascular risk was operationalized as having at least two of these conditions. RESULTS: Analyses were conducted in 1990 participants (mean age 73.2 ± 6.0 years; 54.1 % women). Higher proportions of men than women had hypertension and diabetes, while hyperlipidemia was more prevalent in women. Receiver operating curve analysis indicated relative fat mass was a better predictor of hypertension in women and diabetes in both sexes. Body mass index performed better in predicting hyperlipidemia in women. Relative fat mass thresholds of ≥27 % for men and ≥40 % for women were identified as optimal indicators of heightened cardiovascular risk and so were used to defined high adiposity. Moderate correlations were found between high adiposity or body mass index ≥25 kg/m2 and the presence of hypertension, hyperlipidemia and heightened cardiovascular risk, while a strong correlation was found with diabetes. Logistic regression analysis highlighted significant associations between high adiposity and increased odds of hypertension, diabetes, and heightened cardiovascular risk. CONCLUSIONS: Proposed cut-offs for relative fat mass were more reliable indices than the usual cut-offs for body mass index for identifying individuals at heightened cardiovascular risk. Our findings support the role of anthropometric measures in evaluating body composition and the associated metabolic and cardiovascular conditions in older adults.