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Background Low muscle strength is a powerful predictor of negative health‐related events and a key component of sarcopenia. The lack of normative values for muscle strength across ages hampers the practical appraisal of this parameter. The aim of the present study was to produce normative values for upper and lower extremity muscle strength across a wide spectrum of ages, in a large sample of community‐dwellers recruited in the Longevity check‐up (Lookup) 7+ project. Methods Lookup 7+ is an ongoing project that started in June 2015 and conducted in unconventional settings (i.e. exhibitions, malls, and health promotion campaigns) across Italy with the aim of fostering the adoption of healthy lifestyles in the general population. Candidate participants are eligible for enrolment if they are 18+ years and provide written informed consent. Upper and lower extremity muscle strength is assessed by handgrip strength and five‐repetition chair‐stand [5 × sit‐to‐stand (STS)] tests, respectively. Cross‐sectional centile and normative values for handgrip strength and 5 × STS tests from age 18 to 80+ years were generated for the two genders. Smoothed normative curves for the two tests were constructed for men and women using the lambda‐mu‐sigma method. Results From 1 June 2015 to 30 May 2019, 11 448 participants were enrolled. The mean age of participants was 55.6 years (standard deviation: 11.5 years; range: 18–98 years), and 6382 (56%) were women. Normative values for handgrip strength and the 5 × STS test, both absolute and normalized by body mass index, were obtained for men and women, stratified by age groups. Values of upper and lower extremity muscle strength across ages identified three periods in life: an increase to peak in young age and early adulthood (18–24 years), preservation through midlife (25–44 years), and a decline from midlife onwards (45+ years). Conclusions Our study established age‐specific and gender‐specific percentile reference values for handgrip strength and the 5 × STS test. The normative curves generated can be used to interpret the assessment of muscle strength in everyday practice for the early detection of individuals with or at risk of sarcopenia.

Background. Urolithiasis is the process of stone formation in the urinary tract. Its etiology is only partly known, and efficient therapeutic approaches are currently lacking. Metabolomics is increasingly used in biomarkers discovery for its ability to identify mediators of relevant (patho)physiological processes. Amino acids may be involved in kidney stone formation. The aim of the present study was to investigate the presence of an amino acid signature in stone former urine through a targeted metabolomic approach. Methods. A panel of 35 amino acids and derivatives was assessed in urines from 15 stone former patients and 12 healthy subjects by UPLC-MS. Partial Least Squares Discriminant Analysis (PLS-DA) was used to define amino acid profiles of cases and controls. Results and Discussion. Our approach led to the definition of a specific amino acid fingerprint in people with kidney stones. A urinary amino acid profile of stone formers was characterized by lower levels of α-aminobutyric acid, asparagine, ethanolamine, isoleucine, methionine, phenylalanine, serine, tryptophan, and valine. Metabolomic analysis may lend insights into the pathophysiology of urolithiasis and allow tracking this prevalent condition over time.

Dopaminergic nigrostriatal denervation and widespread intracellular α-synuclein accumulation are neuropathologic hallmarks of Parkinson’s disease (PD). A constellation of peripheral processes, including metabolic and inflammatory changes, are thought to contribute to neurodegeneration. In the present study, we sought to obtain insight into the multifaceted pathophysiology of PD through the application of a multi-marker discovery approach. Fifty older adults aged 70+, 20 with PD and 30 age-matched controls were enrolled as part of the EXosomes in PArkiNson Disease (EXPAND) study. A panel of 68 circulating mediators of inflammation, neurogenesis and neural plasticity, and amino acid metabolism was assayed. Biomarker selection was accomplished through sequential and orthogonalized covariance selection (SO-CovSel), a multi-platform regression method developed to handle highly correlated variables organized in multi-block datasets. The SO-CovSel model with the best prediction ability using the smallest number of variables was built with seven biomolecules. The model allowed correct classification of 94.2 ± 3.1% participants with PD and 100% controls. The biomarker profile of older adults with PD was defined by higher circulating levels of interleukin (IL) 8, macrophage inflammatory protein (MIP)-1β, phosphoethanolamine, and proline, and by lower concentrations of citrulline, IL9, and MIP-1α. Our innovative approach allowed identifying and evaluating the classification performance of a set of potential biomarkers for PD in older adults. Future studies are warranted to establish whether these biomolecules could serve as biomarkers for PD as well as unveil new targets for interventions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11357-020-00192-2) contains supplementary material, which is available to authorized users.

Thirst has been defined as "the sensation that leads animal's and human's actions toward the goal of finding and drinking water" or as "any drive that can motivate water intake, regardless of cause". Thirst, together with xerostomia, is the main cause of poor adherence to fluid restriction and of excessive intake of fluids in patients on chronic hemodialysis, and consequently of high interdialytic weight gain. Interdialytic weight gain (IDWG) should be lower than 4.0-4.5% of dry weight. Unfortunately, many patients have an IDWG greater than this value and some have IDWG of 10-20%. High IDWG is associated with a higher risk of all-cause and cardiovascular death and increased morbidity, such as ventricular hypertrophy and major adverse cardiac and cerebrovascular events. In addition, high IDWG leads to supplementary weekly dialysis sessions with consequent deterioration of quality of life and increased costs. Thus, the knowledge of thirst in patients on chronic hemodialysis is essential to prompt its adequate management to limit IDWG in the routine clinical practice. The present review aims to describe the physiology of thirst in patients on chronic hemodialysis, as well as the prevalence, its measures, the associated variables, the consequences, and the strategies for its reduction.

The evaluation of the physical domain represents a critical part of the assessment of the older person, both in the clinical as well as the research setting. To measure physical function, clinicians and researchers have traditionally relied on instruments focusing on the capacity of the individual to accomplish specific functional tasks (e.g., the Activities of Daily Living [ADL] or the Instrumental ADL scales). However, a growing number of physical performance and muscle strength tests has been developed in parallel over the past three decades. These measures are specifically designed to: 1) provide objective results (not surprisingly, they are frequently timed tests) taken in standardized conditions, whereas the traditional physical function scales are generally self- or proxy-reported measures; 2) be more sensitive to changes; 3) capture the real biology of the function through the assessment of standardized tasks mirroring specific functional subdomains; and 4) mirror the quality of specific mechanisms underlying more complex and multidomain functions. Among the most commonly used instruments, the usual gait speed test, the Short Physical Performance Battery, the handgrip strength, the Timed Up-and-Go test, the 6-minute walk test, and the 400-meter walk test are widely adopted by clinicians and researchers. The clinical and research importance of all these instruments has been demonstrated by their predictive capacity for negative health-related outcomes (i.e., hospitalization, falls, institutionalization, disability, mortality). Moreover, they have shown to be associated with subclinical and clinical conditions that are also not directly related to the physical domain (e.g., inflammation, oxidative stress, overall mortality). For this reason, they have been repeatedly indicated as markers of wellbeing linked to the burden of multiple chronic conditions rather than mere parameters of mobility or strength. In this work protocols of the main tests for the objective assessment of physical function in older adults are presented.

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

BACKGROUND Physical frailty and sarcopenia show extensive clinical similarities. Whether biomarkers exist that are shared by the two conditions is presently unclear. METHODS We conducted a systematic review and meta-analysis of cross-sectional and longitudinal studies that investigated the association of frailty and/or sarcopenia with biomarkers as a primary or secondary outcome in adults aged 60 years and older. Only studies published in English that defined frailty using a validated scale and/or questionnaire and diagnosed sarcopenia according to the presence of muscle atrophy plus dynapenia or low physical function were included. Studies were identified from a systematic search of MEDLINE and SCOPUS databases from inception through August 2020. The quality of reporting of each study was assessed by using the Quality Assessment Tool for Observational Cohort, Cross-Sectional and Case-Control studies of the National Institute of Health. A meta-analysis was conducted when at least three studies investigated the same biomarker in both frailty and sarcopenia. Pooled effect size was calculated based on standard mean differences and random-effect models. Sensitivity analysis was performed based on age and the setting where the study was conducted. RESULTS Eighty studies (58 on frailty and 22 on sarcopenia) met the inclusion criteria and were included in the qualitative analysis. Studies on frailty included 33,160 community-dwellers, hospitalized, or institutionalized older adults (60-88 years) from 21 countries. Studies on sarcopenia involved 4904 community-living and institutionalized older adults (68-87.6 years) from 9 countries. Several metabolic, inflammatory, and hematologic markers were found to be shared between the two conditions. Albumin and hemoglobin were negatively associated with both frailty and sarcopenia. Interleukin 6 was associated with frailty and sarcopenia only in people aged

From the beginning of 2020, the world has been fighting the SARS-Cov-2 outbreak. The life of each one of us has profoundly changed. Unavoidably, our clinical routine has drastically modified in its priorities and methodologies (1). The COVID-19 pandemic has also raised significant issues in the field of research. The investigators’ responsibility has increased with the need to thoughtfully weigh the risk-benefit ratio for each protocol in an emergency and evolving scenario (2).

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.

Background and purpose Cutoff points for physical function tests are commonly used in clinical practice for the evaluation, monitoring, and treatment of older adults. Previous studies have shown that, while age-related patterns of muscle strength change are similar between ethnic groups, strength values differ significantly independent of age. Whether the same applies to other physical function tests is presently unclear. This study investigated age- and gender-related changes of performance on a battery of physical function tests in Brazilian community dwellers. Methods The study followed a cross-sectional design. Participants were community-dwelling adults. Candidates were considered eligible if they were 18 years or older, lived independently, and possessed sufficient physical and cognitive abilities to perform all of the measurements required by the protocol. Physical function tests included isometric handgrip (IHG), 5 times sit-to-stand (5×STS) test, Timed Up and Go, 1-leg stance, and walking speed (WS) at usual and fast pace. Results Two-thousand eight-hundred and four people were enrolled. Mean age was 68.0 (7.0) years (range 50-102 years), and 2262 (80.7%) were women. Men displayed better IHG and balance, while women showed higher performance on the 5×STS and WS tests. A gender-specific pattern of decline in physical performance was observed. Specifically, women showed a linear age-dependent decline in all tests. In men, only in the IHG, 1-leg stance, and WS test at a fast pace was there a linear decline with age. In both genders, the lowest mean values of physical function tests were higher than the proposed cutoffs for sarcopenia. Discussion and conclusions Our findings indicate that the performance on different physical function tests decreases with advancing age in Brazilian adults, following a gender-specific pattern. In none of the tests did the lowest mean values reach the cutoffs for sarcopenia. This suggests that region-specific cutoffs might be necessary to identify older people at risk of adverse events.

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

During aging and menopausal transition in women, a progressive muscle degeneration (i.e. decrease in quality and muscle function) occurs. This muscle dysfunction, caused by decreased proliferation of muscle satellite cells, increased levels of inflammatory markers, and altered levels of sex hormones, exposes women to a raised incidence of sarcopenia. In this regard, hormonal balance and, in particular, estradiol, seems to be essential in skeletal muscle function. The role of the estradiol on satellite cells and the release of inflammatory cytokines in menopausal women are reviewed. In particular, estradiol has a beneficial effect on the skeletal muscle by stimulating satellite cell proliferation. Skeletal muscle can respond to estrogenic hormonal control due to the presence of specific receptors for estradiol at the level of muscle fibers. Additionally, estradiol can limit inflammatory stress damage on skeletal muscle. In this review, we primarily focused on the role of estradiol in sarcopenia and on the possibility of using Estradiol Replacement Therapy, which combined with nutritional and physical activity programs, can counteract this condition representing a valid tool to treat sarcopenia in women.

Traditional healthcare paradigms rely on the disease-centered approach aiming at reducing human nature by discovering specific drivers and biomarkers that cause the advent and progression of diseases. This reductive approach is not always suitable to understand and manage complex conditions, such as multimorbidity and cancer. Multimorbidity requires considering heterogeneous data to tailor preventing and targeting interventions. Personalized Medicine represents an innovative approach to address the care needs of multimorbid patients considering relevant patient characteristics, such as lifestyle and individual preferences, in opposition to the more traditional “one-size-fits-all” strategy focused on interventions designed at the population level. Integration of omic (e.g., genomics) and non-strictly medical (e.g., lifestyle, the exposome) data is necessary to understand patients’ complexity. Artificial Intelligence can help integrate and manage heterogeneous data through advanced machine learning and bioinformatics algorithms to define the best treatment for each patient with multimorbidity and cancer. The experience of an Italian research hospital, leader in the field of oncology, may help to understand the multifaceted issue of managing multimorbidity and cancer in the framework of Personalized Medicine.

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

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

Objectives Symptom persistence weeks after laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance is a relatively common long-term complication of Coronavirus disease 2019 (COVID-19). Little is known about this phenomenon in older adults. The present study aimed at determining the prevalence of persistent symptoms among older COVID-19 survivors and identifying symptom patterns. Design Cross-sectional study. Setting and Participants We analyzed data collected in people 65 years and older (n = 165) who were hospitalized for COVID-19 and then admitted to the Day Hospital Post-COVID 19 of the Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS (Rome, Italy) between April and December 2020. All patients tested negative for SARS-CoV-2 and met the World Health Organization criteria for quarantine discontinuation. Measures Patients were offered multidisciplinary individualized assessments. The persistence of symptoms was evaluated on admission using a standardized questionnaire. Results The mean age was 73.1 ± 6.2 years (median 72, interquartile range 27), and 63 (38.4%) were women. The average time elapsed from hospital discharge was 76.8 ± 20.3 days (range 25−109 days). On admission, 137 (83%) patients reported at least 1 persistent symptom. Of these, more than one-third reported 1 or 2 symptoms and 46.3% had 3 or more symptoms. The rate of symptom persistence was not significantly different when patients were stratified according to median age. Compared with those with no persistent symptoms, patients with symptom persistence reported a greater number of symptoms during acute COVID-19 (5.3 ± 3.0 vs 3.3 ± 2.0; P < .001). The most common persistent symptoms were fatigue (53.1%), dyspnea (51.5%), joint pain (22.2%), and cough (16.7%). The likelihood of symptom persistence was higher in those who had experienced fatigue during acute COVID-19. Conclusions and Implications Persistent symptoms are frequently experienced by older adults who have been hospitalized for COVID-19. Follow-up programs should be implemented to monitor and care for long-term COVID-19–related health issues.

Background Systemic vascular involvement in COVID-19 has been identified in several patients: not only endothelial derangement and increased permeability are reported to be early hallmarks of organ damage in patients with COVID-19 but are also the most important cause of worsening of clinical conditions in severe cases of SARS-CoV-2 infection. There are several reasons to hypothesize that the eye, and the retina in particular, could be a target of organ damage in SARS-CoV-2 infection. Methods This cohort observational study analyzes OCT angiography and structural OCT of 70 post-COVID-19 patients evaluated at 1-month hospital discharge and 22 healthy control subjects. Primary outcomes were macular vessel density (VD) and vessel perfusion (VP); structural OCT features were evaluated as secondary outcomes. In addition, patients and healthy volunteers were evaluated for best corrected visual acuity, slit lamp photograph, and fundus photo image. Results VD and VP in 3 × 3 and 6 × 6 mm scans for SCP and DCP showed no significant differences between the groups. Similarly, CMT and GCL did not reveal significant differences between post-COVID-19 and healthy patients. Nine patients (12.9%) featured retinal cotton wool spots and 10 patients had vitreous fibrillary degeneration. The prevalence of epiretinal membrane and macular hole was similar in the two groups. One case of extra papillary focal retinal hemorrhage was reported in the post-COVID-19 group. Conclusions Macula and perimacular vessel density and perfusion resulted unaltered in mild post-COVID-19 patients at 1-month hospital discharge, suggesting no or minimal retinal vascular involvement by SARS-CoV-2.

BACKGROUND Lack of energy is a symptom frequently complained by older people, leading to the inability to continue functioning at the expected level of activity. This study aimed to investigate whether nutritional status was associated with lack of energy in nursing home (NH) residents. METHODS This was a cross-sectional study. A total of 570 NH residents (72.1% women) in 13 French NHs from the Incidence of pNeumonia and related ConseqUences in nursing home Residents study cohort were included in the study. Lack of energy was measured by the question "Did you feel full of energy during the past week?" from the geriatric depression scale. Nutritional status was evaluated according to Mini Nutritional Assessment Short-Form (MNA-SF). Unadjusted and adjusted logistic regression models were performed to test the association of nutritional status with lack of energy. RESULTS The mean age of participants was 86.5 (SD 7.5) years. A total of 246 NH residents (43.2%) reported a lack of energy. Overall, 71 (12.5%) residents were malnourished and 323 (56.7%) residents were at risk of malnutrition. Malnutrition was significantly associated with lack of energy (OR = 3.42, 95% CI = 1.92-6.08, P

Introduction: Intellectual disability, accelerated aging, and early-onset Alzheimer-like neurodegeneration are key brain pathological features of Down syndrome (DS). Although growing research aims at the identification of molecular pathways underlying the aging trajectory of DS population, data on infants and adolescents with DS are missing. Methods: Neuronal-derived extracellular vesicles (nEVs) were isolated form healthy donors (HDs, n = 17) and DS children (n = 18) from 2 to 17 years of age and nEV content was interrogated for markers of insulin/mTOR pathways. Results: nEVs isolated from DS children were characterized by a significant increase in pIRS1Ser636, a marker of insulin resistance, and the hyperactivation of the Akt/mTOR/p70S6K axis downstream from IRS1, likely driven by the higher inhibition of Phosphatase and tensin homolog (PTEN). High levels of pGSK3βSer9 were also found. Conclusions: The alteration of the insulin-signaling/mTOR pathways represents an early event in DS brain and likely contributes to the cerebral dysfunction and intellectual disability observed in this unique population., Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 18 (8), ISSN:1552-5279, ISSN:1552-5260

Pancreatic cancer (PC) is among the most devastating digestive tract cancers worldwide. This cancer is characterized by poor diagnostic detection, lack of therapy, and difficulty in predicting tumorigenesis progression. Although mutations of key oncogenes and oncosuppressor involved in tumor growth and in immunosurveillance escape are known, the underlying mechanisms that orchestrate PC initiation and progression are poorly understood or still under debate. In recent years, the attention of many researchers has been concentrated on the role of extracellular vesicles and of a particular subset of extracellular vesicles, known as exosomes. Literature data report that these nanovesicles are able to deliver their cargos to recipient cells playing key roles in the pathogenesis and progression of many pancreatic precancerous conditions. In this review, we have summarized and discussed principal cargos of extracellular vesicles characterized in PC, such as miRNAs, lncRNAs, and several proteins, to offer a systematic overview of their function in PC progression. The study of extracellular vesicles is allowing to understand that investigation of their secretion and analysis of their content might represent a new and potential diagnostic and prognostic tools for PC.

Parkinson’s Disease (PD) is a highly prevalent neurodegenerative disease among older adults. PD neuropathology is marked by the progressive loss of the dopaminergic neurons of the substantia nigra pars compacta and the widespread accumulation of misfolded intracellular α-synuclein (α-syn). Genetic mutations and post-translational modifications, such as α-syn phosphorylation, have been identified among the multiple factors supporting α-syn accrual during PD. A decline in the clearance capacity of the ubiquitin-proteasome and the autophagy-lysosomal systems, together with mitochondrial dysfunction, have been indicated as major pathophysiological mechanisms of PD neurodegeneration. The accrual of misfolded α-syn aggregates into soluble oligomers, and the generation of insoluble fibrils composing the core of intraneuronal Lewy bodies and Lewy neurites observed during PD neurodegeneration, are ignited by the overproduction of reactive oxygen species (ROS). The ROS activate the α-syn aggregation cascade and, together with the Lewy bodies, promote neurodegeneration. However, the molecular pathways underlying the dynamic evolution of PD remain undeciphered. These gaps in knowledge, together with the clinical heterogeneity of PD, have hampered the identification of the biomarkers that may be used to assist in diagnosis, treatment monitoring, and prognostication. Herein, we illustrate the main pathways involved in PD pathogenesis and discuss their possible exploitation for biomarker discovery.

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.

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.

COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, showed higher severity and lethality in male older adults . There are currently no specific treatments. Studies are evaluating the efficacy of monoclonal antibodies against interleukin-6 receptor. Here we present the case of a 98-years old man admitted to our COVID-Hospital with acute respiratory failure. Comprehensive geriatric assessment showed no signs of frailty. First-line therapy with hydroxychloroquine and anticoagulants was not effective. Patient was administered intravenous monoclonal antibodies, and he showed remarkable clinical improvement. This case suggests that age alone should not preclude access to new therapeutic approaches. Comprehensive, multisciplinary, multidomain approaches are needed to develop patient-tailored treatments against COVID-19.

Mitochondrial dysfunction and iron (Fe) dyshomeostasis are invoked among the mechanisms contributing to muscle aging, possibly via a detrimental mitochondrial&ndash, iron feed-forward loop. We quantified the labile Fe pool, Fe isotopes, and the expression of mitochondrial Fe handling proteins in muscle biopsies obtained from young and older adults. The expression of key proteins of mitochondrial quality control (MQC) and the abundance of the mitochondrial DNA common deletion (mtDNA4977) were also assessed. An inverse association was found between total Fe and the heavier Fe isotope (56Fe), indicating an increase in labile Fe abundance in cells with greater Fe content. The highest levels of labile Fe were detected in old participants with a Short Physical Performance Battery (SPPB) score &le, 7 (low-functioning, LF). Protein levels of mitoferrin and frataxin were, respectively, higher and lower in the LF group relative to young participants and older adults with SPPB scores &ge, 11 (high-functioning, HF). The mtDNA4977 relative abundance was greater in old than in young participants, regardless of SPPB category. Higher protein levels of Pink1 were detected in LF participants compared with young and HF groups. Finally, the ratio between lipidated and non-lipidated microtubule-associated protein 1A/1B-light chain 3 (i.e., LC3B II/I), as well as p62 protein expression was lower in old participants regardless of SPPB scores. Our findings indicate that cellular and mitochondrial Fe homeostasis is perturbed in the aged muscle (especially in LF older adults), as reflected by altered levels of mitoferrin and frataxin, which, together with MQC derangements, might contribute to loss of mtDNA stability.

The global toll of type 1 diabetes (T1D) has steadily increased over the last decades. It is now widely acknowledged that T1D pathophysiology is more complex than expected. Indeed, a multifaceted interplay between genetic, metabolic, inflammatory and environmental factors exists that leads to heterogeneous clinical manifestations across individuals. Children with non-secretor phenotype and those affected by T1D share low abundance of bifidobacteria, low content of short-chain fatty acids, intestinal phosphatase alkaline and a high incidence of inflammatory bowel diseases. In this context, host-gut microbiota dyad may represent a relevant contributor to T1D development and progression due to its crucial role in shaping host immunity and susceptibility to autoimmune conditions. The FUT2 gene is responsible for the composition and functional properties of glycans in mucosal tissues and bodily secretions, including human milk. FUT2 polymorphisms may profoundly influence gut microbiota composition and host susceptibility to viral infections and chronic inflammatory disease. In this minireview, the possible interplay between mothers' phenotype, host FUT2 genetic background and gut microbiota composition will be discussed in perspective of the T1D onset. The study of FUT2-gut microbiota interaction may add a new piece on the puzzling T1D etiology and unveil novel targets of intervention to contrast T1D development and progression. Dietary interventions, including the intake of α-(1, 2)-fucosyl oligosaccharides in formula milk and the use of specific prebiotics and probiotics, could be hypothesized.

Aim The present study investigated whether hypertension, blood pressure, and antihypertensive therapy were associated with frailty status in community-dwelling older adults. In addition, we tested whether such associations were consistent across different frailty instruments. Material and methods Two-hundred older adults were enrolled in the study. Participant frailty status was determined according to a modified physical frailty phenotype (mFP), the FRAIL scale, and the Study of Osteoporotic Fracture (SOF) index. Blood pressure was assessed three times, in three different days, and mean values were used in the final analysis. Information pertaining to disease conditions and antihypertensive therapy were collected by two researchers through self-report and careful review of medical charts. Results No significant differences in hemodynamic parameters, hypertension diagnosis, and antihypertensive therapy were observed across frailty statuses, regardless of the frailty assessment tool used. Conclusion Findings of the present study indicate that hypertension, blood pressure levels and antihypertensive medication were not cross-sectionally associated with frailty status in cognitively preserved community-dwelling older adults with low prevalence of comorbidities, regardless of the tool used for frailty identification.

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.

Sterile inflammation develops as part of an innate immunity response to molecules released upon tissue injury and collectively indicated as damage-associated molecular patterns (DAMPs). While coordinating the clearance of potential harmful stimuli, promotion of tissue repair, and restoration of tissue homeostasis, a hyper-activation of such an inflammatory response may be detrimental. The complex regulatory pathways modulating DAMPs generation and trafficking are actively investigated for their potential to provide relevant insights into physiological and pathological conditions. Abnormal circulating extracellular vesicles (EVs) stemming from altered endosomal-lysosomal system have also been reported in several age-related conditions, including cancer and neurodegeneration, and indicated as a promising route for therapeutic purposes. Along this pathway, mitochondria may dispose altered components to preserve organelle homeostasis. However, whether a common thread exists between DAMPs and EVs generation is yet to be clarified. A deeper understanding of the highly complex, dynamic, and variable intracellular and extracellular trafficking of DAMPs and EVs, including those of mitochondrial origin, is needed to unveil relevant pathogenic pathways and novel targets for drug development. Herein, we describe the mechanisms of generation of EVs and mitochondrial-derived vesicles along the endocytic pathway and discuss the involvement of the endosomal-lysosomal in cancer and neurodegeneration (i.e., Alzheimer's and Parkinson's disease).

Objectives: The present study aimed at investigating the prevalence of prefrailty and frailty in South American older adults according to the setting and region. Design: A literature search combining the terms “frailty”, “South America” or a specific country name was performed on PubMed, EMBASE, Lilacs, and Scielo to retrieve articles published in English, Portuguese or Spanish on or before August 2019. Participants: Older adults aged 60+ years from any setting classified as frail according to a validated scale were included in the study. Measurements: Frailty assessment by a validated scale. Results: One-hundred eighteen reports (98 performed from Brazil, seven from Chile, five from Peru, four from Colombia, two from Ecuador, one from Argentina, and one from Venezuela) were included in the study. The mean prevalence of prefrailty in South America was 46.8% (50.7% in older in-patients, 47.6% in the community, and 29.8% in nursing-home residents). The mean prevalence of frailty in South America was 21.7% (55.8% in nursing-home residents, 39.1% in hospitalized older adults, and 23.0% in the community). Conclusions: Prefrailty and frailty are highly prevalent in South American older adults, with rates higher than those reported in Europe and Asia. In the community, almost one-in-two is prefrail and one-in-five is frail, while hospitalized persons and nursing-home residents are more frequently affected. These findings indicate the need for immediate attention to avoid frailty progression toward negative health outcomes. Our findings also highlight the need for specific guidelines for the management of frailty in South America.

Frailty is a geriatric syndrome that refers to a state of reduced resiliency to stressful events that occurs in response to physiological and/or psychosocial detriments. Frailty is a predictor of poor prognosis, given that frail older adults are at higher risk of many adverse health-related events. Hence, the identification of potential strategies to prevent the development and progression of frailty is of extreme importance for avoiding its negative outcomes. An adequate protein consumption is advocated as a possible intervention for the management of frailty in older adults due to its effects on muscle mass and physical function. However, empirical evidence is still needed to support this proposition. On the other hand, substantial evidence from observational studies has provided important information on the association between frailty and dietary protein-related parameters. Here, we provide a narrative review of the current literature regarding the association between protein intake (amount (how much?), quality (what type?), and distribution across meals (when?)) and frailty-related parameters. The ultimate aim of this work is to offer practical, evidence-based indications to healthcare professionals responsible for the care of frail older adults.

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

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

Oxidative stress develops as a response to injury and reflects a breach in the cell’s antioxidant capacity. Therefore, the fine-tuning of reactive oxygen species (ROS) generation is crucial for preserving cell’s homeostasis. Mitochondria are a major source and an immediate target of ROS. Under different stimuli, including oxidative stress and impaired quality control, mitochondrial constituents (e.g., mitochondrial DNA, mtDNA) are displaced toward intra- or extracellular compartments. However, the mechanisms responsible for mtDNA unloading remain largely unclear. While shuttling freely within the cell, mtDNA can be delivered into the extracellular compartment via either extrusion of entire nucleoids or the generation and release of extracellular vesicles. Once discarded, mtDNA may act as a damage-associated molecular pattern (DAMP) and trigger an innate immune inflammatory response by binding to danger-signal receptors. Neuroinflammation is associated with a large array of neurological disorders for which mitochondrial DAMPs could represent a common thread supporting disease progression. The exploration of non-canonical pathways involved in mitochondrial quality control and neurodegeneration may unveil novel targets for the development of therapeutic agents. Here, we discuss these processes in the setting of two common neurodegenerative diseases (Alzheimer’s and Parkinson’s disease) and Down syndrome, the most frequent progeroid syndrome.

The present study investigated and compared the patterns of dietary protein intake and physical function in Brazilian and Italian older women. Seventy-five Brazilian older women were recruited in a community senior center. Fifty-three age-matched Italian older women were selected from participants of the Longevity check-up (Lookup) 7+ study. In both samples, physical performance was evaluated by isometric handgrip strength (IHG) and five-time sit-to-stand (5 &times, STS) tests, while diet was assessed through 24-h recall. Results indicated that Brazilian women had a higher intake of plant-based protein (52.7% vs. 30.5% kcal), while Italian women consumed greater amounts of animal-derived protein (29.7% vs. 41.5% kcal). In Brazilian women, the binary logistic regression analysis indicated that body weight-adjusted protein consumption was associated with IHG adjusted by body mass index and with 5 &times, STS performance. In the Italian sample, the intake of isoleucine, leucine, and valine was significantly associated with 5 &times, STS performance. Our findings indicate that Brazilian and Italian community-dwelling older women show different patterns of protein intake, with higher consumption of plant-based protein in the Brazilian sample and higher ingestion of animal-derived protein in the Italian subgroup. These dietary patterns may differentially impact the relationship between physical function and protein intake observed in Brazilian and Italian older women.

Background: The aetiology of postdialysis fatigue (PDF), an intermittent but debilitating fatigue occurring after haemodialysis (HD) treatment, is still unclear. In other inflammatory diseases, increasing evidence points toward the involvement of the immune system in the onset of fatigue symptoms. Altered serum levels of inflammatory cytokines have also been shown in HD patients. Therefore, we investigated whether pre- and postdialysis serum levels of pro- and anti-inflammatory cytokines (i.e. IL-1β, IL-6, TNF-α and IL-10) or their intradialytic changes (if any) were related to PDF or the time HD patients reported needing to recover from HD treatment (TIRD). Methods: Serum levels of IL-1β, IL-6, TNF-α and IL-10 were measured immediately before and after HD in 45 patients using commercially available kits on an ELLA™ automated immunoassay system. The presence and severity of PDF as well as TIRD duration were assessed by self-report measures. Key results: Seventy-four percent of patients reported PDF, with a median PDF severity index of 3.30 [IQR: 3.00–4.30] on a scale from 1 to 5. Median TIRD was 120 min [IQR: 60–480]. PDF severity correlated strongly with TIRD, rs = 0.85, p < 0.001. Only predialysis levels of IL-10 significantly and positively correlated with PDF severity (rs = 0.43, p = 0.003). Conclusion: Findings of the present study do not support the involvement of the immune system in the onset of PDF or the time patients needed to recover from HD treatment. A positive, but counterintuitive relationship was found between predialysis levels of anti-inflammatory IL-10 and PDF severity, which warrants further research.

The present study compared the effects of traditional resistance training (TRT) and combined power training (PT) and TRT (PTRT) on cognitive parameters and serum brain-derived neurotrophic factor (BDNF) levels in non-demented, well-functioning, community-dwelling older women. Forty-five older women were randomized into one of three experimental groups: TRT, PTRT, and control group (CG). Cognitive tests explored global cognitive function, short-term memory, and dual-task performance. Serum BDNF levels were assessed at baseline and after the intervention. Exercise sessions were performed twice a week over 22 weeks. In TRT, exercise sessions were based on three sets of 8&ndash, 10 repetitions at &ldquo, difficult&rdquo, intensity. In PTRT, the first session was based on PT (three sets of 8&minus, moderate&rdquo, intensity), while the second session was similar to the TRT. Our analyses indicated that overall cognitive function, short-term memory, and dual-task performance were similarly improved after TRT and PTRT. Serum BDNF concentrations were not altered by any training protocol. In conclusion, the two RT programs tested in the present trial improved global cognitive function, short-term memory and dual task performance in non-demented, well-functioning, community-dwelling older women. In addition, our findings suggest that mechanisms other than BDNF may be associated with such improvements.

Cardiovascular health (CVH) and physical performance (PP) are key factors of successful ageing. This study investigated whether self-reported CVH behaviours and self-rated health (SRH) are related to ideal CVH and PP. Cross-sectional survey. Public places in Italy (e.g. exhibitions, malls, health promotion campaigns), outside of conventional healthcare settings. 1415 community-living persons aged 65+ years (mean age 72.2 ± 5.4; 58.4% female). Three ideal CVH behaviors [regular physical activity (PA), healthy diet, no smoking] and SRH (1 excellent — 4 poor) were assessed through a brief questionnaire. Four ideal CVH factors [iBMI ≤ 25 kg/m2, untreated random total blood cholesterol ≤200 mg/dl, absence of diabetes (untreated random blood glucose ≤200 mg/dl), untreated blood pressure (iBP)

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