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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. [ABSTRACT FROM AUTHOR]

Regular engagement in physical activity (PA) or physical exercise (PE) is effective at improving physical performance and body composition in older adults. Less is known about the benefits that may be obtained through combining PA with PE and whether the effects of activity habits differ between men and women. This study cross-sectionally investigated the association of PA and/or PE with physical performance and anthropometric measures in a large and relatively unselected sample of older adults enrolled in the Longevity Check-up (Lookup) 7+ project. Participants were individuals 65 years and older living in the community who were recruited in unconventional settings across Italy. Adherence to PA or PE was operationalized as involvement in light walking or various types of exercise, respectively, at least twice weekly for a minimum of 30 min per session throughout the last 12 months. Physical performance measures included handgrip strength and five-time sit-to-stand (5STS) tests. Lower-limb muscle power and appendicular skeletal muscle mass (ASM) were estimated through validated equations. We analyzed data of 4119 participants, of whom 2222 (53.4%) were women. The mean age was 72.8 ± 5.8 years in men and 72.1 ± 5.4 years in women. Regular engagement in PA + PE was reported by 139 (7.3%) men and 100 (4.5%) women. Results indicated that regular walking activity and/or PE were significantly associated with better physical performance and greater ASM with sex-specific patterns. Associations were also influenced by the type of activity, physical performance assessment tool, and anthropometric parameters. Men engaged in PA + PE performed better on the 5STS test and had greater handgrip strength, ASM, and relative and specific muscle power than those practicing either PA or PE. In women, the combination of PA and PE was associated with greater handgrip strength. The findings of this study indicate that older adults regularly practicing PA + PE had better physical performance than those who only engaged in either modality. In men, the combination of PA and PE was also associated with greater ASM. [ABSTRACT FROM AUTHOR]

The present study was conducted to test the association between adherence to specific exercise modalities and sarcopenia severity in Italian older adults. Data were collected as part of the ongoing Longevity Check-Up 7+ (Lookup 7+) project. Lookup 7+ began in June 2015 and has since been conducted in unconventional settings (e.g., exhibitions, malls, social events) throughout Italy. In the present study, we used data on adults 65 years and older. Sarcopenia was identified according to the simultaneous presence of dynapenia and low appendicular muscle mass. Muscle strength was measured by isometric handgrip and sit-to-stand (STS) testing. Sarcopenia was categorized as severe if participants reported difficulty or inability to walk 400 m. Engagement in running and/or swimming (RS) or strength training with or without stretching (SS) was used to define exercise modalities. Analyses were conducted in 3289 participants (mean age: 72.7 ± 5.7 years; 1814 women). The results of the binary regression showed negative associations between RS and the presence of STS-based sarcopenia in women, and between RS and STS-based severe sarcopenia in men. Collectively, these findings indicate that RS is negatively associated with the presence of sarcopenia in large sample of relatively unselected Italian older adults. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Relative fat mass (RFM) predicted hypertension in women and diabetes in both sexes. • Relative fat masses of ≥27% for men and ≥40% for women were optimal cutoffs for classifying high adiposity. • High adiposity correlated with hypertension, diabetes, and having two or more risk factors for cardiovascular disease. • RFM is a reliable measure for identifying older individuals at heightened cardiovascular risk. 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. Retrospective cross-sectional study. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Introduction: The present study investigated the association between protein intake and cognitive function in older adults. Methods: We performed a literature search with no restriction on publication year in MEDLINE, SCOPUS, CINAHL, AgeLine from inception up to October 2020. Observational studies that investigated as a primary or secondary outcome the association of protein intake and cognitive function in older adults aged ⩾60 years were included. Results: Nine cross-sectional studies that investigated a total of 4929 older adults were included in the qualitative analysis. Overall cognitive function was examined in 6 studies. Four investigations reported null associations and 2 studies found that older adults with a high protein intake had higher global cognitive function than their counterparts. Results from the meta-analysis suggested that there were no significant associations between protein consumption and global cognitive function in older adults, regardless of gender. Three studies investigated other cognitive domains. Memory and protein intake were significantly and positively correlated in all studies. In addition, visuospatial, verbal fluency, processing speed, and sustained attention were positively associated with protein consumption in 1 study each. Conclusion: No significant associations between protein intake and global cognitive function were observed in neither qualitative nor quantitative analyses. The association between protein consumption with multiple other cognitive domains were also tested. As a whole, 3 studies reported a positive and significant association between high protein intake and memory, while 1 study observed a significant and positive association with visuospatial, verbal fluency, processing speed, and sustained attention. [ABSTRACT FROM AUTHOR]

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. • Sarcopenia is a prototypical geriatric condition recapitulating all aging hallmarks. • Molecular analyses on muscle biopsies do not capture dynamic muscle changes. • Cost-effective and accessible biomarkers of sarcopenia are highly sought after. • Inflammatory and metabolic mediators are candidate biomarkers of sarcopenia. • Multimarker analysis may assist in capturing the complexity of sarcopenia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: The present study investigated the association between protein intake and cognitive function in older adults. Methods: We performed a literature search with no restriction on publication year in MEDLINE, SCOPUS, CINAHL, AgeLine from inception up to October 2020. Observational studies that investigated as a primary or secondary outcome the association of protein intake and cognitive function in older adults aged ⩾60 years were included. Results: Nine cross-sectional studies that investigated a total of 4929 older adults were included in the qualitative analysis. Overall cognitive function was examined in 6 studies. Four investigations reported null associations and 2 studies found that older adults with a high protein intake had higher global cognitive function than their counterparts. Results from the meta-analysis suggested that there were no significant associations between protein consumption and global cognitive function in older adults, regardless of gender. Three studies investigated other cognitive domains. Memory and protein intake were significantly and positively correlated in all studies. In addition, visuospatial, verbal fluency, processing speed, and sustained attention were positively associated with protein consumption in 1 study each. Conclusion: No significant associations between protein intake and global cognitive function were observed in neither qualitative nor quantitative analyses. The association between protein consumption with multiple other cognitive domains were also tested. As a whole, 3 studies reported a positive and significant association between high protein intake and memory, while 1 study observed a significant and positive association with visuospatial, verbal fluency, processing speed, and sustained attention. [ABSTRACT FROM AUTHOR]

• Dynapenia is part of the diagnostic criteria for sarcopenia. • Isometric handgrip and sit-to-stand tests are recommended as similar proxies of muscle strength. • The association of these measurement tools with whole-body muscle strength and physical function differs significantly. • Studies are needed to refine current recommendations for sarcopenia diagnosis. Sarcopenia is a neuromuscular disease characterized by the simultaneous existence of reduced muscle strength and muscle atrophy. The current recommendations for the diagnosis of sarcopenia suggest dynapenia be operationalized using either isometric handgrip strength (IHG) or sit-to-stand (STS) tests. However, specific associations between each of these assessment tools and sarcopenia-related parameters have been observed. In addition, important neuromuscular and biomechanical aspects differ between IHG and STS. This scenario has important clinical implications and calls for detailed studies to refine the current recommendations for sarcopenia identification. The present communication presents evidence to foster a constructive debate on the matter. [ABSTRACT FROM AUTHOR]

Abstract Sarcopenia, the progressive and generalised loss of muscle mass and strength/function, is a major health issue in older adults given its high prevalence and burdensome clinical implications. Over the years, this condition has been endorsed as a marker for discriminating biological from chronological age. However, the absence of a unified operational definition has hampered its full appreciation by healthcare providers, researchers and policy-makers. In addition to this unsolved debate, the complexity of musculoskeletal ageing represents a major challenge to the identification of clinically meaningful biomarkers. Here, we illustrate the advantages of biomarker discovery procedures in muscle ageing based on multivariate methodologies as an alternative approach to traditional single-marker strategies. The rationale, design and methods of the "BIOmarkers associated with Sarcopenia and PHysical frailty in EldeRly pErsons" (BIOSPHERE) study are described as an application of a multi-marker strategy for the development of biomarkers for the newly operationalised Physical Frailty & Sarcopenia condition. Highlights • Physical Frailty & Sarcopenia (PF&S) is a prevalent condition in older adults. • No reliable biomarkers are presently available to diagnose or track PF&S. • A multi-marker approach may be suitable to capture the complexity of PF&S. • BIOSPHERE will test the association of multiple biomarkers with PF&S. • The multi-marker panel may be used to frame PF&S in clinics and research. [ABSTRACT FROM AUTHOR]

Background Primordial prevention is essential for promoting cardiovascular health and longevity through the so-called seven cardiovascular health metrics (CHMs) (i.e. smoking, body mass index, diet, physical activity, blood pressure, blood glucose and total cholesterol). Measures of muscle mass and function are recognized as powerful predictors of health-related events and survival. Therefore, the present study was undertaken to assess the prevalence and distribution of the seven CHMs and measures of muscle mass and function in an unselected cohort of community-dwellers. Methods The Longevity check-up 7+ (Lookup 7+) project is an ongoing cross-sectional survey conducted in unconventional settings (e.g. exhibitions, malls and health promotion campaigns) across Italy. CHMs are assessed through a brief questionnaire and by measurement of standing height, body weight, blood glucose, blood cholesterol and blood pressure. Muscle mass is estimated from calf circumference, whereas muscle strength and function are measured via handgrip strength and chair-stand testing, respectively. Results Analyses were conducted in 6323 community-living adults (mean age: 54 ± 15 years, 57% women) recruited between 1 June 2015 and 30 June 2017. Participants presented on average 4.3 ± 1.3 ideal CHMs, which decreased with age. Only 19.5% of participants met >5 ideal metrics, while 8.3% met <3. All seven ideal metrics were met by 4.7% of enrollees. Muscle mass, strength and function declined progressively with age, starting at 45–50 years. Conclusion Our population showed suboptimal CHMs scores, with very low prevalence of all ideal metrics. The number of ideal metrics decreased progressively with age and so did muscle mass and function. [ABSTRACT FROM AUTHOR]

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

The maintenance of muscle function into late life protects against various negative health outcomes. The present study was undertaken to evaluate the impact of habitual physical activity and exercise types on physical performance across ages in community-living adults. The Longevity check-up 7+ (Lookup 7+) project is an ongoing cross-sectional survey conducted in unconventional settings (e.g., exhibitions, malls, and health promotion campaigns across Italy) that began on June 1st 2015. The project was designed to raise awareness in the general population on major lifestyle behaviors and risk factors for chronic diseases. Candidate participants are eligible for enrolment if they are at least 18 years of age and provide written informed consent. Physical performance is evaluated through the 5-repetition chair stand test. Analyses were conducted in 6,242 community-living adults enrolled between June 1st 2015 and June 30th 2017, after excluding 81 participants for missing values of the variables of interest. The mean age of the 6,242 participants was 54.4 years (standard deviation 15.2, range 18–98 years), and 3552 (57%) were women. The time to complete the chair stand test was similar from 18 to 40–44 years, and declined progressively across subsequent age groups. Overall, the performance on the chair stand test was better in physically active participants, who completed the test with a mean of 0.5 s less than sedentary enrollees (p < .001). After adjusting for potential confounders, a different distribution of physical performance across exercise intensities was observed, with better performance being recorded in participants engaged in more vigorous activities. Our findings suggest that regular physical activity modifies the age-related pattern of decline in physical performance, with greater benefits observed for more intensive activities. Efforts are needed from health authorities and healthcare providers to promote the large-scale adoption of an active lifestyle throughout the life course. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

The present study explored cross-sectional and longitudinal associations between protein intake and physical function in older adults. We conducted a systematic review and meta-analysis of cross-sectional and longitudinal studies that investigated the association between protein intake and measures of physical function in older adults. Cross-sectional, case-control, and longitudinal cohort studies that investigated the association between protein intake and physical function as a primary or secondary outcome in people aged 60 + years were included. Studies published in languages other than English, Italian, Portuguese, or 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 (SMD), MD, log odds ratio (OR) and Z-score.. Twenty-two cross-sectional studies examined a total of 11,332 community-dwellers, hospitalized older adults, and elite senior athletes with a mean age of approximately 75 years. The pooled analysis indicated that a protein intake higher than the recommended dietary allowance (RDA) was significantly associated with higher Short Physical Performance Battery (SPPB) scores (SMD: 0.63, 95% CI: 0.27, 0.99, P-value: 0.0006), faster walking speed, greater lower-limb (SMD: 0.22, 95% CI: 0.04, 0.40, P-value: 0.02) and isometric handgrip strength (Z-score: 0.087, 95% CI: 0.046–0.128, P-value: 0.0001), and better balance (SMD: 0.33, 95% CI: 0.05, 0.62, P-value: 0.02). Nine longitudinal studies investigated 12,424 community-dwelling and native older adults with a mean age of approximately 85 years. A protein intake higher than the current RDA was not associated with lower decline in either isometric handgrip strength (logOR: 0.99, 95% CI: 0.97–1.02, P-value= 0.67) or walking speed (logOR: 0.92, 95% CI: 0.77–1.10, P-value= 0.35). A protein intake higher than the RDA is cross-sectionally associated with better physical performance and greater muscle strength in older adults. However, a high consumption of proteins does not seem to prevent physical function decline over time. • A protein intake higher than the current RDA is significantly associated with numerous several physical performance tests. • A protein intake higher than the current RDA is not longitudinally associated with upper-limb muscle strength and mobility. • No clear associations were found between protein distribution or sources and physical function. [ABSTRACT FROM AUTHOR]

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. Prospective cohort study. Population-based study. 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. All-cause mortality over 10 years according to the low ASM estimated by calf circumference. 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). 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. [ABSTRACT FROM AUTHOR]

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

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

Abstract: Aging is accompanied by a progressive increase in the incidence and prevalence of cardiovascular disease (CVD). Prolonged exposure to cardiovascular risk factors, together with intrinsic age-dependent declines in cardiac functionality, increases the vulnerability of the heart to both endogenous and exogenous stressors, ultimately enhancing the susceptibility to developing CVD in late life. Both increased levels of oxidative damage and the accumulation of dysfunctional mitochondria have been observed in a wide range of cardiac diseases, which may therefore represent a common ground upon which many aspects of CVD develop. In this review, we summarize the current knowledge on the mechanisms whereby oxidative stress arising from mitochondrial dysfunction is involved in the process of cardiac aging and in the pathogenesis of CVD highly prevalent in late life (e.g., heart failure and ischemic heart disease). Special emphasis is placed on recent evidence about the role played by alterations in cellular quality control systems, in particular autophagy/mitophagy and mitochondrial dynamics (fusion and fission), and their interconnections in the context of age-related CVD. Cardioprotective interventions acting through the modulation of mitochondrial autophagy (calorie restriction, calorie restriction mimetics, and the gasotransmitter hydrogen sulfide) are also presented. This article is part of a Special Issue entitled “Protein Quality Control, the Ubiquitin Proteasome System, and Autophagy”. [Copyright &y& Elsevier]

Abstract: Background: Aging is characterized by derangements in multiple metabolic pathways that progressively constrict the homeostatic reserve (homeostenosis). The signature of metabolic alterations that accompany aging can be retrieved through the metabolomic profiling of biological fluids. Objective: To characterize the age-related changes in urinary and fecal metabolic profiles of BALB/c mice through a 1H nuclear magnetic resonance (NMR)-based metabolomic approach. Methods: Young (n=19) and old (n=13) male BALB/c mice were fed ad libitum standard laboratory chow. Twenty four-hour feces and urine were collected using metabolic cages and analyzed by high-resolution 1H NMR spectroscopy combined with multivariate statistical analyses. Results: An age-related metabolic phenotype was detected both in urine and feces. The metabolic signature of aging consisted of changes in levels of metabolites associated with amino acid metabolism, tricarboxylic acid cycle, tryptophan–nicotinamide adenine dinucleotide pathway, and host–microbiota metabolic axis. Conclusions: Our 1H NMR-based metabolomic approach was able to characterize the effect of age on urinary and fecal metabotypes. The implementation of this analytical strategy may increase our understanding of the metabolic alterations involved in the aging process and assist in the design of anti-aging interventions. [Copyright &y& Elsevier]

Abstract: Sarcopenia, the age-related loss of muscle mass and function, imposes a dramatic burden on individuals and society. The development of preventive and therapeutic strategies against sarcopenia is therefore perceived as an urgent need by health professionals and has instigated intensive research on the pathophysiology of this syndrome. The pathogenesis of sarcopenia is multifaceted and encompasses lifestyle habits, systemic factors (e.g., chronic inflammation and hormonal alterations), local environment perturbations (e.g., vascular dysfunction), and intramuscular specific processes. In this scenario, derangements in skeletal myocyte mitochondrial function are recognized as major factors contributing to the age-dependent muscle degeneration. In this review, we summarize prominent findings and controversial issues on the contribution of specific mitochondrial processes – including oxidative stress, quality control mechanisms and apoptotic signaling – on the development of sarcopenia. Extramuscular alterations accompanying the aging process with a potential impact on myocyte mitochondrial function are also discussed. We conclude with presenting methodological and safety considerations for the design of clinical trials targeting mitochondrial dysfunction to treat sarcopenia. Special emphasis is placed on the importance of monitoring the effects of an intervention on muscle mitochondrial function and identifying the optimal target population for the trial. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting. [Copyright &y& Elsevier]

Recently, we showed that administration of the angiotensin-converting enzyme inhibitor enalapril to aged rats attenuated muscle strength decline and mitigated apoptosis in the gastrocnemius muscle. The aim of the present study was to investigate possible mechanisms underlying the muscle-protective effects of enalapril. We also sought to discern the effects of enalapril mediated by nitric oxide (NO) from those independent of this signaling molecule. Eighty-seven male Fischer 344 × Brown Norway rats were randomly assigned to receive enalapril ( n = 23), the NO synthase (NOS) inhibitor N-nitro- l-arginine methyl ester ( l-NAME; n = 22), enalapril + l-NAME ( n = 19), or placebo ( n = 23) from 24 to 27 months of age. Experiments were performed on the tibialis anterior muscle. Total NOS activity and the expression of neuronal, endothelial, and inducible NOS isoforms (nNOS, eNOS, and iNOS) were determined to investigate the effects of enalapril on NO signaling. Transcript levels of tumor necrosis factor-alpha (TNF-α) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) were assessed to explore actions of enalapril on inflammation and mitochondrial biogenesis, respectively. Protein expression of energy-sensing and insulin signaling mediators, including protein kinase B (Akt-1), phosphorylated Akt-1 (pAkt-1), mammalian target of rapamycin (mTOR), AMP-activated protein kinase subunit alpha (AMPKα), phosphorylated AMPKα (pAMPKα), and the glucose transporter GLUT-4, was also determined. Finally, the generation of hydrogen peroxide (HO) was quantified in subsarcolemmal (SSM) and intermyofibrillar (IFM) mitochondria. Enalapril increased total NOS activity, which was prevented by l-NAME co-administration. eNOS protein content was enhanced by enalapril, but not by enalapril + l-NAME. Gene expression of iNOS was down-regulated by enalapril either alone or in combination with l-NAME. In contrast, protein levels of nNOS were unaltered by treatments. The mRNA abundance of TNF-α was reduced by enalapril relative to placebo, with no differences among any other group. PCG-1α gene expression was unaffected by enalapril and lowered by enalapril + l-NAME. No differences in protein expression of Akt-1, pAkt-1, AMPKα, pAMPKα, or GLUT-4 were detected among groups. However, mTOR protein levels were increased by enalapril compared with placebo. Finally, all treatment groups displayed reduced SSM, but not IFM HO production relative to placebo. Our data indicate that enalapril induces a number of metabolic adaptations in aged skeletal muscle. These effects result from the concerted modulation of NO and angiotensin II signaling, rather than from a dichotomous action of enalapril on the two pathways. Muscle protection by enalapril administered late in life appears to be primarily mediated by mitigation of oxidative stress and pro-inflammatory signaling. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is highly prevalent among older adults and poses a huge burden on morbidity, disability, and mortality. The age-related increased vulnerability of the cardiovascular system towards stressors is a pathophysiological trait of cardiovascular disease. This has been associated with a progressive deterioration of blood vessels and decline in heart function during aging. Cardiomyocytes rely mostly on oxidative metabolism for deploying their activities and mitochondrial metabolism is crucial to this purpose. Dysmorphic, inefficient, and oxidant-producing mitochondria have been identified in aged cardiomyocytes in association with cardiac structural and functional alterations. These aberrant organelles are thought to arise from inefficient mitochondrial quality control, which has therefore been place in the spotlight as a relevant mechanism of cardiac aging. As a result of alterations in mitochondrial quality control and redox dyshomeostasis, mitochondrial damage accumulates and contributes to cardiac frailty. Herein, we discuss the contribution of defective mitochondrial quality control pathways to cardiac frailty. Emerging findings pointing towards the exploitation of these pathways as therapeutic targets against cardiac aging and cardiovascular disease will also be illustrated. • Cardiovascular disease is highly prevalent in older adults. • Cardiomyocytes rely mostly on oxidative metabolism for their function. • Oxidant-producing mitochondria have been identified in aged cardiomyocytes. • Altered mitochondrial quality control and oxidative stress may contribute to cardiac frailty. • Mitophagy and mitochondrial-derived vesicles may be targeted against cardiac aging. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

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

The article discusses a study by M. Chondronikola et al on the effect of prolonged cold-induced BAT activation on whole-body glucose homeostasis and insulin sensitivity involving 7 middle aged, overweight men. Topicis discussed include the study's use of an individualized and prolonged CE protocol that characterized changes induced by maximal nonshivering brown adipose tissue (BAT) thermogenesis and findings that BAT can be exploited for improving systemic glucose homeostasis.

Mitochondria serve as a hub for a multitude of vital cellular processes. To ensure an efficient deployment of mitochondrial tasks, organelle homeostasis needs to be preserved. Mitochondrial quality control (MQC) mechanisms (i.e., mitochondrial dynamics, biogenesis, proteostasis, and autophagy) are in place to safeguard organelle integrity and functionality. Defective MQC has been reported in several conditions characterized by chronic low-grade inflammation. In this context, the displacement of mitochondrial components, including mitochondrial DNA (mtDNA), into the extracellular compartment is a possible factor eliciting an innate immune response. The presence of bacterial-like CpG islands in mtDNA makes this molecule recognized as a damaged-associated molecular pattern by the innate immune system. Following cell death-triggering stressors, mtDNA can be released from the cell and ignite inflammation via several pathways. Crosstalk between autophagy and apoptosis has emerged as a pivotal factor for the regulation of mtDNA release, cell's fate, and inflammation. The repression of mtDNA-mediated interferon production, a powerful driver of immunological cell death, is also regulated by autophagy–apoptosis crosstalk. Interferon production during mtDNA-mediated inflammation may be exploited for the elimination of dying cells and their conversion into elements driving anti-tumor immunity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The present study investigated the impact of resistance training (RT) on cognitive function in older adults with different cognitive status by conducting a systematic review and meta-analysis of intervention studies. We performed a literature search with no restriction on publication year in MEDLINE, Embase, CINAHL, SPORTDiscus, and AgeLine from inception up to August 2020. Experimental studies investigating the impact of RT on the cognitive function of cognitively healthy (CH) and cognitively impaired (CI) older adults (≥60 years) were included for analysis. Eighteen studies were included in the final analysis, of which ten studies investigated CH community-dwelling older adult, seven studies investigated CI older adults, and one study investigated both. RT significantly improved overall cognitive function in both CH (SMD = 0.54; 95% CI = 0.00 to 1.08, P = 0.047) and CI (SMD = 0.60; 95% CI = 0.21 to 1.16, P = 0.005) older adults. However, short-term memory was only improved in CH older adults (MD = −0.20; 95% CI = −0.25 to −0.15, P < 0.00001). In conclusion, RT improved overall cognitive function in CH and CI older adults, whereas short-term memory, assessed by the digit span of the WAIS III, was only significantly improved in CH older adults. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction and failing mitochondrial quality control (MQC) are major determinants of aging. Far from being standalone organelles, mitochondria are intricately related with cellular other compartments, including lysosomes. The intimate relationship between mitochondria and lysosomes is reflected by the fact that lysosomal degradation of dysfunctional mitochondria is the final step of mitophagy. Inter-organelle membrane contact sites also allow bidirectional communication between mitochondria and lysosomes as part of nondegradative pathways. This interaction establishes a functional unit that regulates metabolic signaling, mitochondrial dynamics, and, hence, MQC. Contacts of mitochondria with the endoplasmic reticulum (ER) have also been described. ER-mitochondrial interactions are relevant to Ca2+ homeostasis, transfer of phospholipid precursors to mitochondria, and integration of apoptotic signaling. Many proteins involved in mitochondrial contact sites with other organelles also participate to degradative MQC pathways. Hence, a comprehensive assessment of mitochondrial dysfunction during aging requires a thorough evaluation of degradative and nondegradative inter-organelle pathways. Here, we present a geroscience overview on (1) degradative MQC pathways, (2) nondegradative processes involving inter-organelle tethering, (3) age-related changes in inter-organelle degradative and nondegradative pathways, and (4) relevance of MQC failure to inflammaging and age-related conditions, with a focus on Parkinson's disease as a prototypical geroscience condition. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a leading cause of disability globally. Frailty is a high-impact geriatric condition that increases the risk of negative health outcomes and imposes remarkable health and social burden. Both frailty and T2DM show multifaceted pathophysiology, phenotypic heterogeneity, and fluctuating manifestations that challenge their management, especially when the two conditions co-occur. Muscle wasting and its correlates (e.g., metabolic perturbations and functional decline) that underlie frailty may exacerbates clinical manifestations of T2DM in older people, resulting in worse prognosis. The intrinsic complexity of frailty and T2DM has hampered the identification of clinically meaningful biomarkers to track the clinical progression of the two conditions over time and to monitor the efficacy of pharmacological and lifestyle interventions. Here, we propose an innovative approach for biomarker identification that couples multi-platform analytical determinations with chemometric modeling strategies. This novel multi-marker discovery process is described in the context of the "Metabolic biomarkers of frailty in older people with type 2 diabetes mellitus" (MetaboFrail) study that aimed at identifying metabolic biomarkers of frailty in functionally limited older persons with T2DM. • Frailty and type 2 diabetes (T2DM) are prevalent high-impact condition in older adults. • Muscle wasting and functional decline that underlie frailty may exacerbate clinical manifestations in older people with T2DM. • The complexity of frailty in T2DM should be approached through a multi-marker strategy. • MetaboFrail proposes a novel biomarker discovery process for frailty in T2DM. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in old age. Neurotoxicity of dopaminergic neurons triggered by aggregation of misfolded α-synuclein is a major pathogenic trait of PD. However, growing evidence indicates that peripheral processes, including metabolic changes, may precede and contribute to neurodegeneration. The present study was undertaken to identify a metabolic signature of PD through the quantification of serum amino acids and derivatives. Twenty older adults with PD (11 men and 9 women; mean age 73.1 ± 10.2 years) and 30 age-matched controls (14 men and 16 women; mean age 74.6 ± 4.3 years) were enrolled. A panel of 37 serum amino acids and derivatives was assessed by ultra-performance liquid chromatography/mass spectrometry. Partial least squares − discriminant analysis (PLS-DA) followed by double cross-validation was used to characterize the relationship between amino acid profiles and PD. The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classifications was 99.3 ± 2.5% for participants with PD and 94.7 ± 3.0% for non-PD controls. Higher levels of β-amino butyric acid, cystine, ornithine, phosphoethanolamine, and proline defined the circulating amino acid profile of older people with PD. Controls were characterized by higher concentrations of 3-methyl-histidine, citrulline, and serine. Our findings indicate the existence of a distinct metabotype in older persons with PD. Future studies will have to establish whether changes in amino acid metabolism are involved in the pathogenesis of PD. This knowledge may be harnessed to identify novel disease biomarkers as well as new targets for interventions. • The complex pathophysiology of Parkinsons' disease (PD) hampers a comprehensive appraisal of the condition. • Metabolomics have emerged as a strategy for capturing the complexity of PD. • A specific pattern of circulating amino acids characterizes older adults with PD. • Metabotype analysis may assist early identification of PD in older people. [ABSTRACT FROM AUTHOR]

Aim. The present study investigated the acute effects of low- and high-speed resistance exercise on the cognitive function of frail older women living in nursing home. Materials and Methods. Ten institutionalized frail older women were recruited. Rey Auditory Verbal Learning Test and Stroop test were performed before, immediately after, 1 h after, and 24 h after the end of the experimental session. Participants randomly performed low- and high-speed resistance exercise and a control session. Exercise sessions were composed of 4 resistance exercises with 4–8 sets of 4–10 repetitions at moderate intensity. Results. Results indicated that the performance of Rey Auditory Verbal Learning Test was similarly increased immediately after both low- and high-speed resistance exercises. However, only improvements elicited by low-speed resistance exercise remained significant 1 h after the end of the exercise session. No acute effects of resistance exercise were observed on Stroop performance. Conclusion. Our findings indicated that both low- and high-speed resistance exercises acutely increased episodic memory in frail older women, whereas no changes on Stroop were observed. [ABSTRACT FROM AUTHOR]

Cardiovascular health metrics (CHMs) may predict disability independent of vascular events. Though, the link between CHMs and physical performance is unclear. This relationship was explored using data from the Longevity check-up (Lookup) 7+ project. Lookup 7+ is an ongoing cross-sectional survey conducted in unconventional settings across Italy. People who are at least 18-year-old and provide written informed consent are eligible. CHMs [i.e., smoking status, healthy diet, body mass index (BMI), blood pressure, blood cholesterol, and diabetes status] are assessed through closed questions and objective measurements. Physical performance is measured via the 5-repetition chair-stand test. Analyses included 7446 participants (55.5 ± 14.9 years; 56% women). Physical performance positively correlated with CHMs scores, such that participants who scored higher (6-7 points) completed the chair-stand test about 2 s faster than those scoring lower (1-2 points). In fully adjusted analysis, better physical performance was more frequently observed in younger, non-smoking, physically active men, with ideal BMI, and no diabetes. Our findings indicate a gradient of better physical function with increasing CHMs scores. Future investigations should establish the longitudinal effect of unhealthy behaviours and cardiovascular risk factors on physical performance and verify whether implementation of large-scale primordial cardiovascular prevention may positively impact physical fitness. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) is as a double-stranded molecule existing in hundreds to thousands copies in cells depending on cell metabolism and exposure to endogenous and/or environmental stressors. The coordination of mtDNA replication and transcription regulates the pace of mitochondrial biogenesis to guarantee the minimum number of organelles per cell. mtDNA inheritance follows a maternal lineage, although bi-parental inheritance has been reported in some species and in the case of mitochondrial diseases in humans. mtDNA mutations (e.g., point mutations, deletions, copy number variations) have been identified in the setting of several human diseases. For instance, sporadic and inherited rare disorders involving the nervous system as well higher risk of developing cancer and neurodegenerative conditions, including Parkinson's and Alzheimer's disease, have been associated with polymorphic mtDNA variants. An accrual of mtDNA mutations has also been identified in several tissues and organs, including heart and muscle, of old experimental animals and humans, which may contribute to the development of aging phenotypes. The role played by mtDNA homeostasis and mtDNA quality control pathways in human health is actively investigated for the possibility of developing targeted therapeutics for a wide range of conditions. • Mitochondrial DNA (mtDNA) is a multi-copy genome varying with cell metabolism and stressors. • Heteroplasmic and homoplasmic mtDNA mutations contribute to several disease conditions. • Sporadic and inherited rare disorders of the nervous system hold mtDNA mutations. • Accrual of mtDNA mutations has been reported in several tissues during aging. • mtDNA mutations are implicated in tumorigenesis. [ABSTRACT FROM AUTHOR]

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. • Functional health is pivotal for independent life in old age. • Mitochondrial enzyme deficiency and myofiber loss characterize muscle aging. • Satellite cell decline and inflammation are extrinsic contributors to muscle aging. • The altered autophagy-lysosomal pathway is associated with functional decline. • Muscle structure and mitochondrial quality measures may help frame muscle health. [ABSTRACT FROM AUTHOR]

The present study was conducted to provide normative values for lower-limb muscle power estimated through equations based on the 5 times sit-to-stand (5STS) test in Brazilian older women. In addition, we investigated the association between muscle power parameters and age. The study followed a cross-sectional design. Participants were community-dwelling women. Candidates were considered eligible if they were 18 years or older, lived independently, and possessed sufficient physical and cognitive abilities to perform all measurements required by the protocol. The 5STS test was performed as fast as possible using a standard protocol. Absolute, relative, and allometric muscle power measures were estimated using 5STS-based equations. Two thousand four-hundred seventy-one women participated in the present study. Results indicated that muscle power-related parameters decreased linearly with age. Women 60–69 years showed a marginal reduction in absolute (− 5.2%), relative (− 7.9%), and allometric (− 4.0%) muscle power. A larger reduction was observed in those 70–79 years and reached ¼ of loss in participants ≥ 80, in comparison to middle-aged participants. Pearson's correlation and linear regression analyses indicated that power-related parameters were negatively associated with age. In conclusion, data of the present study provide normative values for lower-limb muscle power parameters according to 5STS-based equations. We observed that muscle power-related parameters declined with age, such that participants 60–69, 70–79, and ≥ 80 years displayed lower absolute and relative muscle power compared middle-aged women. A later decline was observed in allometric muscle power. Relative muscle power declined to a greater extent than other parameters, suggesting a possible window of opportunity for interventions. [ABSTRACT FROM AUTHOR]

Objectives Declining muscle mass and function are hallmarks of the aging process. The preservation of muscle trophism may protect against various negative health outcomes. Age- and sex-specific curves of muscle mass, strength, and function, using data from a large sample of community-dwelling people, are necessary. Material and methods Two surveys (Longevity Check-up and Very Important Protein [VIP]), conducted during EXPO 2015 in Milan, consisted of a population assessment aimed at evaluating the prevalence of specific health metrics in subjects outside of a research setting (n = 3206), with a special focus on muscle mass, strength, and function. Muscle mass was estimated by using mid-arm muscle circumference (MAMC) and calf circumference of the dominant side. Muscle strength and function were assessed through handgrip strength testing and repeated chair stand test, respectively. Results The mean age of 3206 participants in the Longevity Check-up and VIP surveys was 51.9 years (SD 15.6, range 18–98 years), and 1694 (52.8%) were women. Cross-sectional inspection suggests that both calf circumference and MAMC decline nonlinearly with age and the rate of decline varies by gender. These measures are stable until 50 years and then begin to decrease slightly with age, with the effect being more evident in men than in women. The main effect of the age category was observed in muscle strength and physical performance parameters. Muscle strength declined significantly after 45 years of age, both in men and women ( P < .001). The muscle quality of the upper extremities, defined as handgrip strength divided by MAMC, declined significantly with aging, as well ( P < .001). The time to complete the chair stand test was similar from 18 years to 40 to 44 years, and then a linear decline in performing the test across age groups was observed, with an increased time of more than 3 seconds, both in men and women ( P < .001). Conclusions Muscle mass and strength curves may be used to extract reference values for subsequent use in research as well as in the clinical setting. In particular, the analyses of trajectories of muscle parameters may help identify cutoffs for the estimation of risk of adverse events. [ABSTRACT FROM AUTHOR]