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Background. Results regarding the associations between hypertension-related parameters and physical performance in older adults are conflicting. A possible explanation for these divergent results is that investigations may not have adjusted their analyses according to the use of angiotensin-converting enzyme inhibitors (ACEIs). Objectives. To examine the associations between hypertension-related parameters, ACEI use, and a set of physical performance tests in very old adults. Design. Cross-sectional study from the ilSIRENTE database. Setting. Mountain community of the Sirente geographic area (L’Aquila, Abruzzo, Italy). Participants. All persons born in the Sirente area (13 municipalities) before 1 January 1924 and living in that region at the time of study were identified and invited to participate. The final sample included 364 older adults (mean age: 85.8 ± standard deviation [SD] 4.8). Measurements. Physical performance was assessed using isometric handgrip strength (IHG), walking speed (WS) at normal and fast pace, 5-time sit-to-stand test (5STS), and muscle power measures. Blood pressure (BP) was measured after 20 to 40 min of rest, while participants sat in an upright position. Drugs were coded according to the Anatomical Therapeutic and Chemical codes. ACEIs were categorized in centrally (ACEI-c) and peripherally (ACEI-p) acting. Blood inflammatory markers, free insulin-like growth factor 1 (IGF-1), and IGF-binding protein 3 (IGFBP-3) were assayed. Results. Results indicated that 5STS test was significantly and negatively associated with diastolic BP values. However, significance was lost when results were adjusted for ACEI use. Participants on ACEIs were more likely to have greater specific muscle power and higher blood levels of IGFBP-3 than non-ACEI users. When participants were categorized according to ACEI subtypes, those on ACEI-p had higher blood IGF-1 levels compared with ACEI-c users. Conclusions. The main findings of the present study indicate that

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.

Objectives. To examine the relationships between protein intake from various food sources and cardiometabolic risk markers in Italian older adults. Design. Cross-sectional study. Setting: Unconventional settings across Italy (e.g., exhibitions, health promotion campaigns). Participants. People 65+ years who provided a written informed consent. Measurements. Blood pressure (BP), blood glucose, total blood cholesterol, and anthropometric indices were assessed. Daily protein intake was estimated for 12 food items listed in a food frequency questionnaire. Results. Three-thousand four-hundred twenty-four older adults (mean age: 72.7 ± 5.7 years; 55% women) were included in the study. Results of linear regression analysis indicated that protein intake from several food sources was negatively associated with BP, waist and hip circumferences, and waist-to-hip ratio in both sexes. Blood glucose levels were inversely associated with many protein sources in women. Positive associations were observed between some protein sources and total blood cholesterol in both men and women. Conclusion. Our findings suggest that dietary protein is differentially associated with cardiometabolic risk factors depending on sex and food sources.

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Purpose: Hip fracture is a public health problem worldwide. Traditional prognostic models do not include blood biomarkers, such as those obtained by proteomics. This study aimed to investigate the relationships between serum inflammatory biomarkers and frailty in older adults with hip fracture as well as adverse outcomes at one and three months after discharge. Methods: A total of 45 patients aged 75 or older who were admitted for hip fracture were recruited. At admission, a Comprehensive Geriatric Assessment (CGA) was conducted, which included a frailty assessment using the Clinical Frailty Scale (CFS). Blood samples were collected before surgery. Participants were followed up at one and three months after discharge. The levels of 45 cytokines were analyzed using a high-throughput proteomic approach. Binary logistic regression was used to determine independent associations with outcomes, such as functional recovery, polypharmacy, hospital readmission, and mortality. Results: The results showed that IL-7 (OR 0.66 95% CI 0.46-0.94, p = 0.022) and CXCL-12 (OR 0.97 95% CI 0.95-0.99, p = 0.011) were associated with better functional recovery at three months after discharge, while CXCL-8 (OR 1.07 95% CI 1.01-1.14, p = 0.019) was associated with an increased risk of readmission. Conclusions: These findings suggest that immunology biomarkers may represent useful predictors of clinical outcomes in hip fracture patients.

Background: COVID-19 has disproportionately affected older adults. Yet, healthcare trajectories experienced by older persons hospitalized for COVID-19 have not been investigated. This study aimed at estimating the probabilities of transitions between severity states in older adults admitted in COVID-19 acute wards and at identifying the factors associated with such dynamics. Methods: COVID-19 patients aged ≥60 years hospitalized between March and December 2020 were involved in the multicentre GeroCovid project–acute wards substudy. Sociodemographic and health data were obtained from medical records. Clinical states during hospitalization were categorized on a seven-category scale, ranging from hospital discharge to death. Based on the transitions between these states, first, we defined patients’ clinical course as positive (only improvements), negative (only worsening), or fluctuating (both improvements and worsening). Second, we focused on the single transitions between clinical states and estimated their probability (through multistage Markov modeling) and associated factors (with proportional intensity models). Results: Of the 1024 included patients (mean age 78.1 years, 51.1% women), 637 (62.2%) had a positive, 66 (6.4%) had a fluctuating, and 321 (31.3%) had a negative clinical course. Patients with a fluctuating clinical course were younger, had better mobility and cognitive levels, fewer diseases, but a higher prevalence of cardiovascular disease and obesity. Considering the single transitions, the probability that older COVID-19 patients experienced clinical changes was higher within a 10-day timeframe, especially for milder clinical states. Older age, male sex, lower mobility level, multimorbidity, and hospitalization during the COVID-19 first wave (compared with the second one) were associated with an increased probability of progressing towards worse clinical states or with a lower recovery. Conclusion: COVID-19 in older inpatients has a complex and dynam

The present study was conducted to test the association between protein intake and blood pressure, glucose levels, and blood cholesterol in a large sample of Italian older adults. Longevity Check-up 7+ (Lookup 7+) is an ongoing project that started in June 2015. The project is conducted in unconventional settings (e.g., exhibitions, malls, health promotion campaigns) across Italy with the aim of fostering adoption of healthy lifestyles in the general population. For the present study, participants were eligible if they were 65+ years and provided written informed consent. Systolic (SBP) and diastolic blood pressure (DBP), and blood glucose and cholesterol levels were assessed. Protein intake was estimated using a 12-item food frequency questionnaire. Three-thousand four-hundred and four older adults were included in the study. The results of the linear regression showed an inverse association between protein intake (as a continuous variable) and DBP, and a positive correlation with blood cholesterol levels. The findings of the present study indicate that a high intake of protein was negatively associated with DBP and positively associated with total blood cholesterol levels in a large cohort of Italian older adults, after adjustment for numerous covariates.

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

Introduction: Arginine metabolism is involved in the regulation of several biological processes. Many liquid chromatography tandem-mass spectrometry methods for the determination of arginine and its metabolites have been developed but they are time consuming and imply long pre-analytical procedures. The purpose of this study was to develop a rapid method for the simultaneous determination of arginine, citrulline, ornithine, symmetric and asymmetric dimethylarginine and monomethylarginine in human plasma. Materials and methods: The pre-analytical procedure consisted in a simple deproteinization. The chromatographic separation was performed using hydrophilic interaction liquid chromatography. Analytes detection was performed with a triple quadrupole equipped with electrospray ion source operating in positive ion mode. Mass spectrometry experiments were conducted in multiple reaction monitoring mode. Results and conclusions: Recovery ranged from 92.2 to 108.0%. The within-run imprecision and between-run imprecision ranged from 1.5 to 6.8 % and 3.8 to 11.9%, respectively. Carry over and matrix effect did not affect quantitative analysis. Extraction recovery was between 95 and 105 %. Stability after pre-analytical procedure was tested and all the metabolites were stable after 48 h at 4 °C. In conclusion, our novel method allow a rapid and easy determination of arginine and its metabolites both for research and clinical routine use.

Background-Analgesics could be used to manage painful symptoms during and after COVID-19. Materials and methods-Persistence of painful symptoms was assessed during and after COVID-19 in a sample of patients admitted to a post-acute COVID-19 outpatient service in Rome, Italy. Data on type and frequency of use of first-line analgesics were collected. Pain severity was evaluated with a numeric rating scale (NRS) from 0 to 10. Results-Mean age of 696 participants was 57.1 ± 20.3 years and 61.7% were women. During COVID-19, the most prevalent symptoms were fever, fatigue, arthralgia, myalgia and headache. Acetaminophen was used by 40% of the sample. Only 6.7% needed to continue analgesic therapy after COVID-19. Frequent causes of analgesics consumption were persistent arthralgia and myalgia. The most common analgesics used amongst those who continued taking analgesics in the post-acute phase of COVID-19 were the following: acetaminophen (31%), ibuprofen (31%) and other non-steroidal anti-inflammatory drug (NSAID) (29.5%); in older subjects the most common analgesic used was acetaminophen (54%). Most of the subjects in this group said there was an improvement in pain perception after taking analgesic therapy (84%). Conclusions-Use of analgesics in the post-acute COVID-19 is common in subjects with persistent arthralgia and myalgia, and common analgesics were acetaminophen and ibuprofen. Further research on the safety and efficacy of those medications in COVID-19 is warranted.

Background: The present study was conducted to explore the association between protein intake across the main meals and hypertension (HTN)-related parameters in community-dwelling Brazilian older adults. Methods: Brazilian community-dwelling older adults were recruited in a senior center. Dietary habits were assessed through 24 h recall. Protein intake was classified as high and low according to median and recommended dietary allowance values. Absolute and body weight (BW)–adjusted protein consumption levels were quantified and analyzed according to ingestion across the main meals. Systolic (SBP) and diastolic blood pressure (DBP) were measured using an oscilometric monitor. Participants were categorized as hypertensive according to physician diagnosis or the detection of high SBP and/or DBP values. Results: One hundred ninety-seven older adults were enrolled in the present study. Protein intake at lunch was independently and negatively associated with SBP. Furthermore, a lower prevalence of HTN (diagnosed by a physician) was observed in participants with higher intakes of protein. These results remained significant after adjustment for many covariates. However, significance was lost when kilocalories and micronutrients were included in the model. Conclusions: Findings of the present study indicate that protein intake at lunch was independently and negatively associated with systolic BP in community-dwelling older adults.

Background: Ageing is accompanied by a progressive loss of skeletal muscle mass and strength, potentially determining the insurgence of sarcopenia. Evidence suggests that motoneuron and neuromuscular junction (NMJ) degeneration contribute to sarcopenia pathogenesis. Seeking for strategies able to slow down sarcopenia insurgence and progression, we investigated whether a 2-year mixed-model training involving aerobic, strength and balance exercises would be effective for improving or preserving motoneuronal health and NMJ stability, together with muscle mass, strength and functionality in an old, sarcopenic population. Methods: Forty-five sarcopenic elderly (34 females; 11 males) with low dual-energy X-ray absorptiometry (DXA) lean mass and Short Physical Performance Battery (SPPB) score <9 were randomly assigned to either a control group [Healthy Aging Lifestyle Education (HALE), n = 21] or an intervention group [MultiComponent Intervention (MCI), n = 24]. MCI trained three times per week for 2 years with a mix of aerobic, strength and balance exercises matched with nutritional advice. Before and after the intervention, ultrasound scans of the vastus lateralis (VL), SPPB and a blood sample were obtained. VL architecture [pennation angle (PA) and fascicle length (Lf)] and cross-sectional area (CSA) were measured. As biomarkers of neuronal health and NMJ stability status, neurofilament light chain (NfL) and C-terminal agrin fragment (CAF) concentrations were measured in serum. Differences in ultrasound parameters, NfL and CAF concentration and physical performance between baseline and follow-up were tested with mixed ANOVA or Wilcoxon test. The relationship between changes in physical performance and NfL or CAF concentration was assessed through correlation analyses. Results: At follow-up, MCI showed preserved VL architecture (PA, Lf) despite a reduced CSA (−8.4%, P < 0.001), accompanied by maintained CAF concentration and ameli

Extracellular vesicles have been identified as pivotal mediators of intercellular communication with critical roles in physiological and pathological conditions. Via this route, several molecules (e.g., nucleic acids, proteins, metabolites) can be transferred to proximal and distant targets to convey specific information. Extracellular vesicle-associated cargo molecules have been proposed as markers of several disease conditions for their potential of tracking down the generating cell. Indeed, circulating extracellular vesicles may represent biomarkers of dysfunctional cellular quality control systems especially in conditions characterized by the accrual of intracellular misfolded proteins. Furthermore, the identification of extracellular vesicles as tools for the delivery of nucleic acids or other cargo molecules to diseased tissues makes these circulating shuttles possible targets for therapeutic development. The increasing interest in the study of extracellular vesicles as biomarkers resides mainly in the fact that the identification of peripheral levels of extracellular vesicle-associated proteins might reflect molecular events occurring in hardly accessible tissues, such as the brain, thereby serving as a 'brain liquid biopsy'. The exploitation of extracellular vesicles for diagnostic and therapeutic purposed might offer unprecedented opportunities to develop personalized approaches. Here, we discuss the bright and dark sides of extracellular vesicles in the setting of two main neurodegenerative diseases (i.e., Parkinson's and Alzheimer's diseases). A special focus will be placed on the possibility of using extracellular vesicles as biomarkers for the two conditions to enable disease tracking and treatment monitoring.

The most commonly used antiviral treatment against hepatitis C virus is a combination of direct-acting antivirals (DAAs) and ribavirin (RBV), which leads to a shortened duration of therapy and a sustained virologic response until 98%. Nonetheless, several dose-related side effects of RBV could limit its applications. This study aims to measure the urinary concentration of RBV and its main metabolites in order to evaluate the drug metabolism ability of HCV patients and to evaluate the adverse effects, such as anemia, with respect to RBV metabolite levels. RBV and its proactive and inactive metabolites were identified and quantified in the urine of 17 HCV males with severe liver fibrosis using proton nuclear magnetic resonance (1H-NMR) at the fourth week (TW4) and at the twelfth week of treatment (EOT). Four prodrug urinary metabolites, including RBV, were identified and three of them were quantified. At both the TW4 and EOT stages, six HCV patients were found to maintain high concentrations of RBV, while another six patients maintained a high level of RBV proactive metabolites, likely due to nucleosidase activity. Furthermore, a negative correlation between the reduction in hemoglobin (Hb) and proactive forms was observed, according to RBV-triphosphate accumulation causing the hemolysis. These findings represent a proof of concept regarding tailoring the drug dose in relation to the specific metabolic ability of the individual, as expected by the precision medicine approach.

Background: Fatigue with reduced tolerance to exercise is a common persistent long-lasting feature amongst COVID-19 survivors. The assessment of muscle function in this category of patients is often neglected.Aim.: To evaluate the potential impact of a daily supplementation based on amino acids, minerals, vi-tamins, and plant extracts (Apportal (R)) on muscle function, body composition, laboratory parameters and self-rated health in a small group of COVID-19 survivors affected by fatigue.Methods: Thirty participants were enrolled among patients affected by physical fatigue during or after acute COVID-19 and admitted to the post-COVID-19 outpatient service at Fondazione Policlinico Gemelli in Rome between 1st March 2021 and 30th April 2021. All participants were evaluated at first visit (t0) and at control visit (t1), after taking a daily sachet of Apportal (R) for 28 days. Muscle function was analyzed using hand grip strength test, exhaustion strength time and the number of repetitions at one -minute chair stand test. Body composition was assessed with bioelectrical impedance analysis (BIA). Laboratory parameters, including standard blood biochemistry and ferritin levels, were evaluated at the first visit and during the control visit. A quick evaluation of self-rated health, before COVID-19, at t0 and t1, was obtained through a visual analogue scale (VAS). Results: Participants aged 60 years and older were 13 (43%). Females represented the 70% of the study sample. Participants hospitalized for COVID-19 with low -flow oxygen supplementation represented the 43.3% of the study sample while 3.3% received noninvasive ventilation (NIV) or invasive ventilation. Hand grip strength improved from 26.3 Kg to 28.9 Kg (p < 0.05) at t1 as compared to t0. The mean time of strength exhaustion increased from 31.7 s (sec) at t0 to 47.5 s at t1 (p < 0.05). Participants performed a higher number of repetitions (28.3 vs. 22.0; p < 0.05) during the one-minute chair stand test at

Nonconventional clinical presentations of diseases are common in older adults. Even dramatic events, such as foreign body (FB) inhalation, can occur in a subtle and non-specific manner. Pill aspiration is a rare yet overlooked cause of airway injury. It accounts for approximately 7% of all FB aspirations. In contrast, oral dysphagia and polypharmacology, mainly administrated in solid oral dosage forms (SDOF), like tablets and pills, are common conditions in older adults. Herein, we present a case of SDOF aspiration in a 78-year-old man. FB inhalation developed with general clinical deterioration and neurological impairment (delirium) rather than overt respiratory symp-toms. Bronchoscopy provided remarkable images of this unexpected finding. Caregivers and healthcare workers must be aware of the risk of SDOF aspiration and adopt proper safety mea-sures. Early recognition and bronchoscopy for diagnostic and therapeutic purposes can be life-saving in such cases.

The diagnosis of cachexia is based on loss of body weight and low body mass index plus at least three out of five additional criteria: decrease in muscle strength, fatigue, anorexia, low lean body mass, and abnormal biochemistry. Cachexia affects 50-80% of cancer patients, accounting for up to 20% of all cancer-related deaths. Cachexia is associated with increased incidence of doselimiting chemotherapy toxicity and higher odds of treatment discontinuation. Energy wasting resulting from an imbalance between energy requirements and energy uptake is proposed to contribute to cachexia. Muscle protein breakdown, acceleration of myonuclear apoptosis, and impaired muscle regeneration contribute to nitrogen imbalance and muscle wasting in cachexia. Identifying personalised nutritional needs and developing tailored nutritional plans are pillars of cachexia treatment. Substances with muscle anabolic activities may represent a pharmacological option to contrast cachexia. Multimodal treatment protocols should involve a multidisciplinary team of health professionals as well as patients and their formal and informal caregivers.

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.

Long COVID, a condition characterized by symptom and/or sign persistence following an acute COVID-19 episode, is associated with reduced physical performance and endothelial dysfunction. Supplementation of l-arginine may improve endothelial and muscle function by stimulating nitric oxide synthesis. A single-blind randomized, placebo-controlled trial was conducted in adults aged between 20 and 60 years with persistent fatigue attending a post-acute COVID-19 outpatient clinic. Participants were randomized 1:1 to receive twice-daily orally either a combination of 1.66 g l-arginine plus 500 mg liposomal vitamin C or a placebo for 28 days. The primary outcome was the distance walked on the 6 min walk test. Secondary outcomes were handgrip strength, flow-mediated dilation, and fatigue persistence. Fifty participants were randomized to receive either l-arginine plus vitamin C or a placebo. Forty-six participants (median (interquartile range) age 51 (14), 30 [65%] women), 23 per group, received the intervention to which they were allocated and completed the study. At 28 days, l-arginine plus vitamin C increased the 6 min walk distance (+30 (40.5) m; placebo: +0 (75) m, p = 0.001) and induced a greater improvement in handgrip strength (+3.4 (7.5) kg) compared with the placebo (+1 (6.6) kg, p = 0.03). The flow-mediated dilation was greater in the active group than in the placebo (14.3% (7.3) vs. 9.4% (5.8), p = 0.03). At 28 days, fatigue was reported by two participants in the active group (8.7%) and 21 in the placebo group (80.1%; p < 0.0001). l-arginine plus vitamin C supplementation improved walking performance, muscle strength, endothelial function, and fatigue in adults with long COVID. This supplement may, therefore, be considered to restore physical performance and relieve persistent symptoms in this patient population.

The age-associated decrease in appetite and food intake is referred to as "anorexia of aging". Older adults with anorexia show changes in the quantity/quality of energy supplied to the organism which eventually may cause a mismatch between ingested calories and physiological energy demands. Therefore, a state of malnutrition and impaired metabolism may ensue which renders older people more vulnerable to stressors and more prone to incur negative health outcomes. These latter cover a wide range of conditions including sarcopenia, low engagement in physical activity, and more severe consequences such as disability, loss of independence, hospitalization, nursing home placement, and mortality. Malnutrition has been recognized by the European Society of Clinical Nutrition (ESPEN) among the chief risk factors for the development of frailty. Frailty refers to a state of increased vulnerability to stressors stemming from reduced physiologic reserve, and according to ESPEN, is also nutrition-based. Alike frailty, anorexia is highly prevalent among older adults, and its multifactorial nature includes metabolic changes that develop in older age and possibly underly the condition. Circulating factors, including hormones (eg, cholecystokinin, ghrelin, leptin, and inflammatory and microbial mediators of gut dysbiosis), have been proposed as biomarkers for this condition to support early identification and develop personalized nutritional interventions. Additional studies are needed to untangle the interrelationship between gut microbiota and appetite regulation in older adults operating through brain-gut crosstalk. Furthermore, the contribution of the genetic background to appetite regulation and specific nutritional needs warrants investigation. Here, we provide an overview on anorexia of aging in the context of age-related metabolic changes. A special focus is placed on candidate biomarkers that may be used to assist in the early identification of anorexia of aging and in the d

Sarcopenia is an age-related neuromuscular disease characterized by substantial muscle atrophy, dynapenia and/or loss of physical function. Sarcopenia progression increases the risk for numerous negative events, including falls, disability, hospitalization, nursing home placement, and death. As such, this condition is recognized as an important topic in gerontology and geriatrics. The best approach to counteract the development and progression of sarcopenia is actively debated. Resistance training (RT) has received special attention in this context, owing to the large number of studies showing its ability to produce significant improvements in sarcopenia-related parameters. Recommendations to guide RT prescription for older adults with different conditions, including people who have traits of sarcopenia, have been published. Some authors have argued that RT guidelines for older adults are similar to one another, which may indicate that the presence of sarcopenia does not require specific physical exercise programs. However, older people with sarcopenia might present with peculiar physical, biomechanical, physiological, and psychosocial characteristics that, in our view, are not taken into adequate consideration in existing exercise guidelines. Here, we present evidence to support the view that RT prescription for older adults with sarcopenia is complex, multifactorial, and still needs more evidence.

Objectives: The present study investigated the association between religious and spiritual (RS) practices with the prevalence, severity, and incidence of mental health problems in older adults. Methods: We conducted a systematic review and meta-analysis of cross-sectional and longitudinal studies that investigated older adults aged 60+ years and assessed RS using valid scales and questions from valid scales, and mental health according to validated multidimensional or specific instruments. Studies were retrieved from MEDLINE, LILACS, SCOPUS, CINAHL, and AgeLine databases until July 31, 2021. The risk of bias was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS). A pooled effect size was calculated based on the log odds ratio (OR) and Z-scores. This study is registered on PROSPERO. Results: One hundred and two studies that investigated 79.918 community-dwellers, hospitalized, and institutionalized older adults were included. Results indicated that high RS was negatively associated with anxiety and depressive symptoms, while a positive association was observed with life satisfaction, meaning in life, social relations, and psychological well-being. Specifically, people with high spirituality, intrinsic religiosity, and religious affiliation had a lower prevalence of depressive symptoms. In relation to longitudinal analysis, most studies supported that high RS levels were associated with a lower incidence of depressive symptoms and fear of death, as well as better mental health status. Conclusion: Findings of the present study suggest that RS are significantly associated with mental health in older adults. People with high RS levels had a lower prevalence of anxiety and depressive symptoms, as well as reported greater life satisfaction and psychological well-being, better social relations, and more definite meaning in life. Data provided by an increasing number of longitudinal studies have supported most of these findings.

Background: Fatigue with reduced tolerance to exercise is a common persistent long-lasting feature amongst COVID-19 survivors. The assessment of muscle function in this category of patients is often neglected. Aim.: To evaluate the potential impact of a daily supplementation based on amino acids, minerals, vi- tamins, and plant extracts (Apportal®) on muscle function, body composition, laboratory parameters and self-rated health in a small group of COVID-19 survivors affected by fatigue. Methods: Thirty participants were enrolled among patients affected by physical fatigue during or after acute COVID-19 and admitted to the post-COVID-19 outpatient service at Fondazione Policlinico Gemelli in Rome between 1st March 2021 and 30th April 2021. All participants were evaluated at first visit (t0) and at control visit (t1), after taking a daily sachet of Apportal® for 28 days. Muscle function was analyzed using hand grip strength test, exhaustion strength time and the number of repetitions at one- minute chair stand test. Body composition was assessed with bioelectrical impedance analysis (BIA). Laboratory parameters, including standard blood biochemistry and ferritin levels, were evaluated at the first visit and during the control visit. A quick evaluation of self-rated health, before COVID-19, at t0 and t1, was obtained through a visual analogue scale (VAS). Results: Participants aged 60 years and older were 13 (43%). Females represented the 70% of the study sample. Participants hospitalized for COVID-19 with low-flow oxygen supplementation represented the 43.3% of the study sample while 3.3% received noninvasive ventilation (NIV) or invasive ventilation. Hand grip strength improved from 26.3 Kg to 28.9 Kg (p < 0.05) at t1 as compared to t0. The mean time of strength exhaustion increased from 31.7 s (sec) at t0 to 47.5 s at t1 (p < 0.05). Participants performed a higher number of repetitions (28.3 vs. 22.0; p < 0.05) during the one-minute chair stand test at t1

Restrictive measures aimed at containing COVID-19 pandemic had a significant impact on lifestyle habits, quality of life, psychosocial well-being, and mobility in individuals older than 80 years who have not contracted SARS-CoV-2 infection. A comprehensive multidimensional assessment should be routinely implemented to determine and manage the potential negative consequences of public health measures on overall health status and quality of life of older adults.

Aim: To determine the prevalence and associated factors of vitamin D deficiency in COVID-19 survivors and the relationship between vitamin D status and physical performance. Methods: Vitamin D status was assessed in a sample of patients who had recovered from COVID-19 and were admitted to a post-acute outpatient service at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS (Rome, Italy). Participants were offered comprehensive medical assessment, including physical performance and muscle strength tests. Self-rated health was assessed. Vitamin D deficiency was defined as a serum concentration of 25-OH vitamin D < 20 ng/mL. Results: Mean age of 681 participants was 53.4 ± 15.2 years and 49% were women. Vitamin D deficiency was detected in 35.6% of the whole study population, and in 40.2% of those 65 and older. Vitamin D deficiency was associated with diabetes, higher body mass index, and COVID-19 severity, and showed a seasonal pattern with a peak in autumn/winter. Participants with vitamin D deficiency performed poorer on the six-minute walking test, with the lowest performance observed in those 65 and older. No significant associations with any other parameters were found. Conclusion: Our findings indicate that vitamin D deficiency is frequent in COVID-19 survivors, especially in older adults. Low vitamin D levels are associated with poor physical performance, in particular in old age.

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

Background: Severe clinical pictures and sequelae of COVID-19 disease are immune mediated and characterized by a ‘cytokine storm’. Skeletal muscle has emerged as a potent regulator of immune system function. The aim of the present study is to define the prevalence of sarcopenia among COVID-19 survivors and the negative impact of sarcopenia on the post-acute COVID-19 syndrome and its related risk factors. Methods: A total of 541 subjects recovered from COVID-19 disease were enrolled in the Gemelli Against COVID-19 Post-Acute Care between April 2020 and February 2021. They underwent a multidisciplinary clinical evaluation and muscle strength and physical performance assessment. Results: Mean age was 53.1 years (SD 15.2, range from 18 to 86 years), and 274 (51%) were women. The prevalence of sarcopenia was 19.5%, and it was higher in patients with a longer hospital stay and lower in patients who were more physically active and had higher levels of serum albumin. Patients with sarcopenia had a higher number of persistent symptoms than non-sarcopenic patients (3.8 ± 2.9 vs. 3.2 ± 2.8, respectively; P = 0.06), in particular fatigue, dyspnoea, and joint pain. Conclusions: Sarcopenia identified according to the EWGSOP2 criteria is high in patients recovered from COVID-19 acute illness, particularly in those who had experienced the worst clinical picture reporting the persistence of fatigue and dyspnoea. Our data suggest that sarcopenia, through the persistence of inflammation, could be the biological substrate of long COVID-19 syndrome. Physical activity, especially if associated with adequate nutrition, seems to be an important protective factor.

Background: The present systematic review and meta-analysis investigated the cross-sectional and longitudinal associations between protein intake and sarcopenia in older adults. Methods: Observational studies that investigated the association between protein intake and sarcopenia as the primary or secondary outcome in people aged 60 years and older were included. Studies published in languages other than English, Italian, Portuguese, and Spanish were excluded. Studies were retrieved from MEDLINE, SCOPUS, EMBASE, CINAHL, AgeLine, and Food Science Source databases through January 31, 2022. A pooled effect size was calculated based on standard mean differences. Results: Five cross-sectional studies, one longitudinal study, and one case-control study that investigated 3353 community-dwelling older adults with a mean age of approximately 73 years were included. The meta-analysis of four studies indicated that older adults with sarcopenia consumed significantly less protein than their peers with no sarcopenia. Conclusions: Results of the present study suggest that an inadequate protein intake might be associated with sarcopenia in older adults.

Objective: The purpose of the present study was to assess the effect of a specific oral nutritional supplement among patients recovered from COVID-19 but suffering symptoms of fatigue. Methods: This is an observational case–control study involving a sample of 66 COVID-19 survivors divided in two groups, 33 subjects in the intervention group who received the nutritional supplement and 33 subjects in the control group. The nutritional supplement received by subjects in the active group was based on amino acids; vitamin B6 and B1; and malic, succinic and citric acids. After an 8-week follow-up, the main outcomes considered were skeletal muscle index (measured by bioelectrical impedance analysis), physical performance measures (handgrip strength, one-minute chair–stand test, six-minute walking test), and quality of life (using EuroQol visual analogue scale). Results: All the considered areas increased significantly in the subjects receiving the active treatment with oral nutritional supplement in comparison with the baseline values. After adjusting for age, gender, and baseline values, skeletal muscle index, handgrip strength test, the one-minute chair–stand test, and six-minute walking test values were higher among participants in the treatment group compared with subjects in control group. The oral nutritional supplement significantly improved the handgrip strength; similarly, participants in the active group showed a higher improvement in skeletal muscle index, the one-minute chair–stand test, the six-minute walking test, and in quality of life. Conclusion: The nutritional supplement containing nine essential amino acids plus cysteine; vitamin B6 and B1; and malic, succinic and citric acids had a positive effect on nutritional status, functional recovery, and quality of life in COVID-19 survivors still suffering from fatigue. Additional controlled clinical trials are required to corroborate these results.

Objective To determine whether a multicomponent intervention based on physical activity with technological support and nutritional counselling prevents mobility disability in older adults with physical frailty and sarcopenia. Design Evaluator blinded, randomised controlled trial. Setting 16 clinical sites across 11 European countries, January 2016 to 31 October 2019. Participants 1519 community dwelling men and women aged 70 years or older with physical frailty and sarcopenia, operationalised as the co-occurrence of low functional status, defined as a short physical performance battery (SPPB) score of 3 to 9, low appendicular lean mass, and ability to independently walk 400 m. 760 participants were randomised to a multicomponent intervention and 759 received education on healthy ageing (controls). Interventions The multicomponent intervention comprised moderate intensity physical activity twice weekly at a centre and up to four times weekly at home. Actimetry data were used to tailor the intervention. Participants also received personalised nutritional counselling. Control participants received education on healthy ageing once a month. Interventions and follow-up lasted for up to 36 months. Main outcome measures The primary outcome was mobility disability (inability to independently walk 400 m in <15 minutes). Persistent mobility disability (inability to walk 400 m on two consecutive occasions) and changes from baseline to 24 and 36 months in physical performance, muscle strength, and appendicular lean mass were analysed as pre-planned secondary outcomes. Primary comparisons were conducted in participants with baseline SPPB scores of 3-7 (n=1205). Those with SPPB scores of 8 or 9 (n=314) were analysed separately for exploratory purposes. Results Mean age of the 1519 participants (1088 women) was 78.9 (standard deviation 5.8) years. The average follow-up was 26.4 (SD 9.5) months. Among participants with SPPB scores of 3-7, mobility disability occurred in 283/605 (

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Long COVID affects a large share of persons of all age groups but may be especially burdensome for vulnerable older adults. Long COVID has a complex pathophysiology encompassing inflammatory and autoimmune processes, perturbations in metabolic pathways, and alterations in endothelial function and redox homeostasis.The management of long COVID requires a multidimensional approach that should include a comprehensive nutritional assessment. Several food bioactive compounds, nutraceuticals, and supplements may target specific pathways involved in long COVID and may, therefore, be used as an adjunctive therapy to manage the condition.

We recently conducted a systematic review and meta-analysis to assess the association between protein consumption and frailty in older adults [...].

Background: The present systematic review and meta-analysis investigated the cross-sectional and longitudinal associations between protein intake and frailty in older adults. Methods: We conducted a systematic review and meta-analysis of cross-sectional and longitudinal studies that investigated the association between protein intake and frailty in older adults. Cross-sectional, case-control, and longitudinal cohort studies that investigated the association between protein intake and frailty 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 on 31 January 2022. Results: Twelve cross-sectional and five longitudinal studies that investigated 46,469 community-dwelling older adults were included. The meta-analysis indicated that absolute, bodyweight-adjusted, and percentage of protein relative to total energy consumption were not cross-sectionally associated with frailty. However, frail older adults consumed significantly less animal-derived protein than robust people. Finally, high protein consumption was associated with a significantly lower risk of frailty. Conclusions: Our pooled analysis indicates that protein intake, whether absolute, adjusted, or relative to total energy intake, is not significantly associated with frailty in older adults. However, we observed that frail older adults consumed significantly less animal protein than their robust counterparts.

Objective: Low muscle mass is one of the mediators of numerous complications accompanying malnutrition status and sarcopenia and at the same time may have a greater effect on survival than other clinical characteristics. In this study, we evaluated the impact of low appendicular skeletal muscle (ASM) on all-cause mortality risk over 10 years in older community-dwellers. Design: Prospective cohort study. Setting: Population-based study. Participants: All persons aged 80+ years living in the community of the Sirente geographic area (L'Aquila, Italy) (n = 364). Participants were categorised in low or normal ASM based on the COONUT equation that considered calf circumference, age and gender. Primary outcome: All-cause mortality over 10 years according to the low ASM estimated by calf circumference. Results: Low estimated ASM was identified in 128 participants (37 %). A total of 245 deaths were recorded over 10 years: 110 among participants with low ASM (85.3 %) and 135 among persons with normal ASM (65.1 %; p < 0.001). Participants with low ASM had a higher risk of death than those with normal ASM (HR: 3.38; 95 % CI: 1.93–5.93). This association remained statistically significant after adjusting for a number of potential confounders, such as age, gender, ADL impairment, cognitive impairment, BMI, and plasma CRP and IL6 levels (HR: 1.84; 95 % CI: 1.03–3.28). Conclusions: Our findings show that low estimated ASM by calf circumference is predictive of 10 years mortality in older community-dwellers. The derived equation used in the present study to estimate ASM, based on calf circumference, may be particularly relevant in clinical practice. Hence, in older persons with low ASM, interventions targeting muscle mass may be effective at preventing or postponing negative health outcomes.

Inflammaging and SARS-CoV-2 infection interact in an interplay that involves both acute inflammation and low-grade chronic inflammation, predisposing older adults to severe COVID-19. During the acute phase, the precipitating factor is represented by an aberrant immune response characterized by the overproduction of proinflammatory cytokines. Increased cytokine levels may persist long after viral clearance and are potentially responsible for the installment of low-grade chronic inflammation and long-lasting persistence of COVID-19 symptoms. Therapeutic approaches targeting inflammation have proven to be effective in reducing mortality during an acute COVID-19 episode. However, at the time of writing, no standard treatment is available for the postacute phase. Although further research is needed, lifestyle interventions (physical activity and specific nutritional strategies) can effectively counteract chronic inflammation and may therefore be proposed as strategies to mitigate long-term symptom persistence.

Aging induces substantial remodeling of glia, including density, morphology, cytokine expression, and phagocytic capacity. Alterations of glial cells, such as hypertrophy of lysosomes, endosomes and peroxisomes, and the progressive accumulation of lipofuscin, lipid droplets, and other debris have also been reported. These abnormalities have been associated with significant declines of microglial processes and reduced ability to survey the surrounding tissue, maintain synapses, and recover from injury. Similarly, aged astrocytes show reduced capacity to support metabolite transportation to neurons. In the setting of reduced glial activity, stressors and/or injury signals can trigger a coordinated action of microglia and astrocytes that may amplify neuroinflammation and contribute to the release of neurotoxic factors. Oxidative stress and proteotoxic aggregates may burst astrocyte-mediated secretion of pro-inflammatory cytokines, thus activating microglia, favoring microgliosis, and ultimately making the brain more susceptible to injury and/or neurodegeneration. Here, we discuss the contribution of microglia and astrocyte oxidative stress to neuroinflammation and neurodegeneration, highlight the pathways that may help gain insights into their molecular mechanisms, and describe the benefits of antioxidant supplementation-based strategies.

Background: The present study explored cross-sectional and longitudinal associations between protein intake and physical function in older adults. Methods: 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. Results: 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). Conclusions: A protein intake higher tha

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

Background: Demographic changes in the western world entail new clinical approaches and challenges in older persons. Low skeletal muscle mass and low physical performance in older persons are both predisposing conditions for disability and obtaining knowledge in this cohort is essential. Aim: The primary aim of the study was to analyze a broader spectrum of gait characteristics within this specific population and differentiate them across different test conditions. Methods: Two centers participating at the SPRINTT project with hi-tech gait analysis available conducted a cross-sectional descriptive study on N = 115 community-dwelling older persons with low muscle mass and physical performance. Reference values of 13 gait parameters were collected across different conditions: usual gait speed, fast gait speed, and usual gait speed while simultaneously naming animals. Results and discussion: This study shows the first spatio-temporal reference values in a community-dwelling older population composed of individuals with low skeletal muscle mass and low physical performance. In comparison to the normative spatio-temporal gait parameters in older persons reported in the literature, this population showed some differences. The mean gait speed was lower than 1 m/s, considered as a cutoff for vulnerable community-dwelling individuals, which corresponds to a greater risk of falls, hospitalization, and mortality. The stride length variability was higher, exposing to a greater risk of falling, and was also associated with a higher risk of developing cognitive decline. Conclusion: This study represents the first step in the development of quantitative reference values in community-dwelling older persons with low physical performance and low skeletal muscle mass.

Purpose: The present study included two related investigations that explored the acute and chronic effects of high-speed resistance training (HSRT) on blood pressure (BP) in older adults. Methods: The first study involved a randomized crossover study that compared the acute effects of traditional resistance exercise (TRT) and high-speed resistance training (HSRT) on hemodynamic parameters in frail older adults. Sixteen institutionalized frail older adults were recruited. BP was recorded before, over 1 h, and 24 h after the end of the experimental session. Participants performed 4 resistance exercises involving 4–8 sets with 4–10 repetitions at moderate intensity. The second study was a systematic review and meta-analysis of experimental studies that investigated the acute and chronic effects of HSRT on BP in older adults. Crossover, quasi-experimental, and randomized controlled trials that examined the effects of HSRT on BP in people aged 60+ years as a primary or secondary outcome were included. Studies were retrieved from MEDLINE, SPORTDiscuss, CINAHL, SCOPUS and AgeLine databases from inception through December 31, 2021. The risk of bias was evaluated using the Newcastle - Ottawa Quality Assessment Scale (NOS). A pooled effect size was calculated based on standard mean differences (SMD). Results: In study 1, we observed that both TRT and HSRT caused post-exercise hypotension (PEH). However, systolic BP (SBP) was significantly lowered for up to 60 min after TRT, while it was only reduced 30 and 50 min after HSRT. There was no difference in SBP between resistance exercise protocols. A reduction in mean arterial pressure was only observed after TRT. In study 2, 1114 articles were identified, and 8 were included in the meta-analysis. Pooled analyses indicated that HSRT did not cause significant PEH. However, a significant reduction in SBP was observed after HSRT programs in comparison to controls (SMD = 0.61, P = 0.009) and baseline values (SMD = 2.03, P = 0.04). Con

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.

Mitochondria are primarily involved in cell bioenergetics, regulation of redox homeostasis, and cell death/survival signaling. An immunostimulatory property of mitochondria has also been recognized which is deployed through the extracellular release of entire or portioned organelle and/or mitochondrial DNA (mtDNA) unloading. Dynamic homo-and heterotypic interactions involving mitochondria have been described. Each type of connection has functional implications that eventually optimize mitochondrial activity according to the bioenergetic demands of a specific cell/tissue. Inter-organelle communications may also serve as molecular platforms for the extracellular release of mitochondrial components and subsequent ignition of systemic inflammation. Age-related chronic inflammation (inflamm-aging) has been associated with mitochondrial dysfunction and increased extracellular release of mitochondrial components—in particular, cell-free mtDNA. The close relationship between mitochondrial dysfunction and cellular senescence further supports the central role of mitochondria in the aging process and its related conditions. Here, we provide an overview of (1) the mitochondrial genetic system and the potential routes for generating and releasing mtDNA intermediates; (2) the pro-inflammatory pathways elicited by circulating mtDNA; (3) the participation of inter-organelle contacts to mtDNA homeostasis; and (4) the link of these processes with senescence and age-associated conditions.

Background: Physical frailty and sarcopenia show extensive clinical similarities. Whether biomarkers exist that are shared by the two conditions is presently unclear. Methods: We conducted a systematic review and meta-analysis of cross-sectional and longitudinal studies that investigated the association of frailty and/or sarcopenia with biomarkers as a primary or secondary outcome in adults aged 60 years and older. Only studies published in English that defined frailty using a validated scale and/or questionnaire and diagnosed sarcopenia according to the presence of muscle atrophy plus dynapenia or low physical function were included. Studies were identified from a systematic search of MEDLINE and SCOPUS databases from inception through August 2020. The quality of reporting of each study was assessed by using the Quality Assessment Tool for Observational Cohort, Cross-Sectional and Case-Control studies of the National Institute of Health. A meta-analysis was conducted when at least three studies investigated the same biomarker in both frailty and sarcopenia. Pooled effect size was calculated based on standard mean differences and random-effect models. Sensitivity analysis was performed based on age and the setting where the study was conducted. Results: Eighty studies (58 on frailty and 22 on sarcopenia) met the inclusion criteria and were included in the qualitative analysis. Studies on frailty included 33,160 community-dwellers, hospitalized, or institutionalized older adults (60–88 years) from 21 countries. Studies on sarcopenia involved 4904 community-living and institutionalized older adults (68–87.6 years) from 9 countries. Several metabolic, inflammatory, and hematologic markers were found to be shared between the two conditions. Albumin and hemoglobin were negatively associated with both frailty and sarcopenia. Interleukin 6 was associated with frailty and sarcopenia only in people aged < 75. Community-dwelling older adults with frailty and sarcopenia had

Frailty is today a hot topic in the scientific community and among clinicians. Geriatricians are no longer the only specialists discussing this age-related condition. Many medical disciplines (e.g., oncologists (1), cardiologists (2), neurologists (3), nephrologists (4), infectious disease specialists (5), pneumologists (6), anesthesiologists (7)) have finally started looking at this critical aspect in older persons, particularly impactful on prognosis and treatment modalities (e.g., (8, 9)). In the debate about this “novel” condition, it may sometimes happen that the word “frailty” is inappropriately used, suggesting a still incomplete understanding of the condition of interest. Some concepts seem difficult to get through, especially in those fields that are not used to the holistic approach and multidisciplinarity typical of geriatrics.

A context that is overall featuring social and economic changes, improvement in technology, progress in medicine, and better public health care is favorable to a worldwide increase in the elderly population aged over 65 years (Christensen et al., 2009). Prevention in the case of disability proves essential as aging could lead to permanent incapacities (Morley, 2012). Medical care, in particular, and healthcare systems at large are more and more on the alert: they are requested to find the proper solutions and decide on the most efficient answers to the damaging effects of aging. Both sarcopenia (Janssen et al., 2000) and frailty (Clegg et al., 2013), which are quite frequent among the elderly, require specific attention (Cesari et al., 2014). Both are at times linked to health problems (Vetrano et al., 2014) that can possibly be reversible and dealt with via clinical practices (Vellas et al., 2013). Hence, this review will focus on the characterization of sarcopenia in the context of physical frailty (PF).

Introduction: The novel coronavirus SARS-Cov-2 can infect the respiratory tract causing a spectrum of disease varying from mild to fatal pneumonia, and known as COVID-19. Ongoing clinical research is assessing the potential for long-term respiratory sequelae in these patients. We assessed the respiratory function in a cohort of patients after recovering from SARS-Cov-2 infection, stratified according to PaO2/FiO2 (p/F) values. Method: Approximately one month after hospital discharge, 86 COVID-19 patients underwent physical examination, arterial blood gas (ABG) analysis, pulmonary function tests (PFTs), and six-minute walk test (6MWT). Patients were also asked to quantify the severity of dyspnoea and cough before, during, and after hospitalization using a visual analogic scale (VAS). Seventy-six subjects with ABG during hospitalization were stratified in three groups according to their worst p/F values: above 300 (n = 38), between 200 and 300 (n = 30) and below 200 (n = 20). Results: On PFTs, lung volumes were overall preserved yet, mean percent predicted residual volume was slightly reduced (74.8 ± 18.1%). Percent predicted diffusing capacity for carbon monoxide (DLCO) was also mildly reduced (77.2 ± 16.5%). Patients reported residual breathlessness at the time of the visit (VAS 19.8, p < 0.001). Patients with p/F below 200 during hospitalization had lower percent predicted forced vital capacity (p = 0.005), lower percent predicted total lung capacity (p = 0.012), lower DLCO (p < 0.001) and shorter 6MWT distance (p = 0.004) than patients with higher p/F. Conclusion: Approximately one month after hospital discharge, patients with COVID-19 can have residual respiratory impairment, including lower exercise tolerance. The extent of this impairment seems to correlate with the severity of respiratory failure during hospitalization.

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.

This chapter presents multi-marker biomarker discovery as an approach for capturing the complexity of physical frailty and sarcopenia (PFandS), overviews candidate biomarkers for PFandS, and discusses relevant pathways involving these mediators. PFandS has a multifactorial etiology that recapitulates all biological hallmarks of aging. Multi-marker analysis has increasingly been recognized as a complementary and more sophisticated strategy for investigating highly dynamic and complex conditions, including PFandS. The development of biological markers that can be measured in biofluids at any time point and be used in a cost-effective manner to guide the diagnosis and facilitate the monitoring of PFandS are highly sought after. The assessment of clinical, functional, and imaging parameters was used for identifying PFandS. Although paving the way for biomarker discovery, all the reported studies have the caveat of investigating single domains of the PFandS condition.

Beta‐hydroxy‐beta‐methylbutyrate (HMB) is an active metabolite of leucine, a branched‐chain essential amino acid entirely derived from food sources, and it has been studied for many decades (Figure 24.1). HMB per se is present in very small amounts of some foods, such as cauliflower, citrus fruit, avocado, and catfish. HMB is synthesized from leucine in two separate steps occurring in liver and muscle cell [1]. At muscle cells level, leucine has an explicit role in controlling and at the same time regulating protein synthesis, and HMB has an important role as a key active metabolite in this process. Nevertheless, only approximately 5% of leucine that we can eat with the usual diet is converted to HMB, which, in a subject weighing 70–80 kg, ends in the production of 0.2–0.4 g of HMB per day [2].