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

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

Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial.

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.

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

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

Fatigue in Covid-19 survivors: The potential impact of a nutritional supplement on muscle strength and function.

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, vitamins, 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 as compared to t0. A trend, although not significant, in reduction of ferritin levels was found after nutritional supplementation (94.4 vs. 84.3, respectively; p = 0.01). The self-rated health status increased by at least 13 points (t0, mean 57.6 ± 5.86; t1, mean 71.4 ± 6.73; p < 0.05). CONCLUSIONS: After 28 days of nutritional supplementation with Apportal® in COVID-19 survivors affected by fatigue with reduced tolerance to exercise, we found a significant improvement in means of muscle strength and physical performance, associated with enhancement of self-rated health status between t0 and t1.

Nutraceuticals and Dietary Supplements for Older Adults with Long COVID-19.

The persistence of COVID-19 symptoms weeks or months after an initial SARS-CoV-2 infection has become one of the most burdensome legacies of the pandemic. This condition, known as long COVID syndrome, affects many persons of all age groups and is associated with substantial reductions of quality of life. Several mechanisms may be involved in long COVID syndrome, including chronic inflammation, metabolic perturbations, endothelial dysfunction, and gut dysbiosis. These pathogenic mechanisms overlap with those of the aging process and may aggravate pre-existing degenerative conditions. This review discusses bioactive foods, supplements, and nutraceuticals as possible interventions against long COVID syndrome.

Age-Associated Glia Remodeling and Mitochondrial Dysfunction in Neurodegeneration: Antioxidant Supplementation as a Possible Intervention.

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.

Effects of a New Multicomponent Nutritional Supplement on Muscle Mass and Physical Performance in Adult and Old Patients Recovered from COVID-19: A Pilot Observational Case-Control Study.

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.

Frailty prevalence and impact on outcomes in patients with atrial fibrillation: A systematic review and meta-analysis of 1,187,000 patients.

Frailty is a clinical syndrome characterized by a reduced physiologic reserve, increased vulnerability to stressors and an increased risk of adverse outcomes. People with atrial fibrillation (AF) are often burdened by frailty due to biological, clinical, and social factors. The prevalence of frailty, its management and association with major outcomes in AF patients are still not well quantified. We systematically searched PubMed and EMBASE, from inception to September 13th, 2021, for studies reporting the prevalence of frailty in AF patients. The study was registered in PROSPERO (CRD42021235854). 33 studies were included in the systematic review (n = 1,187,651 patients). The frailty pooled prevalence was 39.7 % (95 %CI=29.9 %-50.5 %, I2 =100 %), while meta-regression analyses showed it is influenced by age, history of stroke, and geographical location. Meta-regression analyses showed that OAC prescription was influenced by study-level mean age, baseline thromboembolic risk, and study setting. Frail AF patients were associated with a higher risk of all-cause death (OR=5.56, 95 %CI=3.46-8.94), ischemic stroke (OR=1.59, 95 %CI=1.00-2.52), and bleeding (OR=1.64, 95 %CI=1.11-2.41), when compared to robust individuals. In this systematic review and meta-analysis, the prevalence of frailty was high in patients with AF. Frailty may influence the prognosis and management of AF patients, thus requiring person-tailored interventions in a holistic or integrated approach to AF care.

Religiosity/Spirituality and Mental Health in Older Adults: A Systematic Review and Meta-Analysis of Observational Studies.

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.

Effect of a 40-weeks multicomponent exercise program and branched chain amino acids supplementation on functional fitness and mental health in frail older persons.

BACKGROUND: The ageing process implies several physiological and psychological changes that hence affect the general health, mood states, and quality of life of older persons. Exercise and adequate nutrition are renowned non-pharmacological strategies that significantly delay and alleviate the adverse consequences of the ageing process. This study aimed to evaluate the effects of branched-chain amino acid (BCAA) supplementation and a multicomponent exercise program (ME) on the physical frailty and mood states of older persons. METHODS: 35 participants (women and men; 83 ± 3 years old) from residential care homes were submitted to a 40-week exercise-washout-retraining intervention (16 weeks of the elastic band based exercise and/or supplementation, 8 weeks of washout, and 16 weeks of multicomponent exercise and/or resupplementing), with or without BCAA supplementation. The experimental groups were: (i) ME plus BCAA supplementation (ME+BCAA); (ii) ME; (iii) BCAA supplementation (BCAA), and (iv) control group (CG). Fried's phenotype was used to assess frailty prevalence. Geriatric Depression Scale (GDS), Profile of Mood State (POMS), Mini-Mental State Examination (MMSE), were used to access mental health and cognition. The Short Physical Performance Battery (SPPB) was used to access functional capacity. Salivary testosterone levels (ST) were also determined to access the anabolic effects of the intervention. RESULTS: Exercise was effective in improving functional capacity and prevented the increase in frailty that occurred in the non-exercising CG, where the frailty scores increased over time (p < 0.01). BCAAs supplement alone had no impact on functional fitness, but in a short time (16 weeks) contributed to diminishing frailty and combined with exercise may have the potential to reduce the effect of a detraining period on functional capacity. Salivary testosterone levels correlated with handgrip strength and could be a useful indicator of susceptibility to frailty. No effects were found for mood states, cognition, and depression. CONCLUSION: This study showed that a long-term exercise program, independent of being multicomponent or strength elastic band-based, was effective in improving functional capacity and prevented an increase in frailty in frail and pre-frail older persons living in residential care homes.

Effect of Training-Detraining Phases of Multicomponent Exercises and BCAA Supplementation on Inflammatory Markers and Albumin Levels in Frail Older Persons.

Nowadays, it is accepted that the regular practice of exercise and branched-chain amino acids supplementation (BCAAs) can benefit the immune responses in older persons, prevent the occurrence of physical frailty (PF), cognitive decline, and aging-related comorbidities. However, the impact of their combination (as non-pharmacological interventions) in albumin and the inflammatory markers is not fully understood. Therefore, we investigated the effect of a 40-week multifactorial intervention [MIP, multicomponent exercise (ME) associated or not with BCAAs] on plasma levels of inflammatory markers and albumin in frail older persons (≥75 years old) living at residential care homes (RCH). This study consisted of a prospective, naturalistic, controlled clinical trial with four arms of multifactorial and experimental (interventions-wahshout-interventions) design. The intervention groups were ME + BCAAs (n = 8), ME (n = 7), BCAAs (n = 7), and control group (n = 13). Lower limb muscle-strength, cognitive profile, and PF tests were concomitantly evaluated with plasma levels of albumin, anti- and pro-inflammatory cytokines [Interleukin-10 (IL-10) and Tumor Necrosis Factor-alpha (TNF-α) respectively], TNF-α/IL-10 ratio, and myeloperoxidase (MPO) activity at four different time-points: Baseline (T1), after 16 weeks of multifactorial intervention (T2), then after a subsequent 8 weeks washout period (T3) and finally, after an additional 16 weeks of multifactorial intervention (T4). Improvement of cognitive profile and muscle strength-related albumin levels, as well as reduction in the TNF-α levels were found particularly in ME plus BCAAs group. No significant variations were observed over time for TNF-α/IL-10 ratio or MPO activity. Overall, the study showed that MIP triggered slight alterations in the inflammatory and physical function of the frail older participants, which could provide independence and higher quality of life for this population.

Effects of a New Combination of Medical Food on Endothelial Function and Lipid Profile in Dyslipidemic Subjects: A Pilot Randomized Trial.

Nutritional approaches to improve dyslipidemias have been recently developed, but evidences on different medical foods are often incomplete. The main aim of our study was to evaluate the effects on endothelial function, lipid profile, and glucose metabolism of two different combinations of nutraceuticals, first one containing Bergavit (200 mg Citrus bergamia), Omega-3 (400 mg), Crominex 3+ (10 mcg trivalent chromium), and red yeast rice (100 mg; 5 mg monacolin K) and second one containing red yeast rice (200 mg; 3 mg monacolin K), Berberine (500 mg), Astaxanthin (0.5 mg), folic acid (200 mcg), Coenzyme Q10 (2 mg), and Policosanol (10 mg). Fifty subjects affected by dyslipidemia not requiring statin treatment were enrolled in this randomized, blind, controlled trial and submitted to blood sampling for lipid and glucose profiles and instrumental evaluation of endothelial function before and after 6 weeks of treatment with nutraceuticals. Both nutraceutical combinations improved the lipid profile; the nutraceutical containing 5 mg of monacolin K, 200 mg of the extract Citrus bergamia, 400 mg of Omega-3, and 10 mcg of trivalent chromium entailed a significant improvement of endothelial function with enhanced cholesterol lowering effect. In conclusion, this study confirms the positive effect of functional food on lipid profile and endothelial function in absence of major undesirable effects.

Beta-hydroxy-beta-methylbutyrate and sarcopenia: from biological plausibility to clinical evidence.

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

Dietary supplementation with acetyl-l-carnitine counteracts age-related alterations of mitochondrial biogenesis, dynamics and antioxidant defenses in brain of old rats.

We previously reported the ability of dietary supplementation with acetyl-l-carnitine (ALCAR) to prevent age-related decreases of mitochondrial biogenesis in skeletal muscle and liver of old rats. Here, we investigate the effects of ALCAR supplementation in cerebral hemispheres and cerebellum of old rats by analyzing several parameters linked to mitochondrial biogenesis, mitochondrial dynamics and antioxidant defenses. We measured the level of the coactivators PGC-1α and PGC-1ß and of the factors regulating mitochondrial biogenesis, finding an age-related decrease of PGC-1ß, whereas PGC-1α level was unvaried. Twenty eight-month old rats supplemented with ALCAR for one and two months showed increased levels of both factors. Accordingly, the expression of the two transcription factors NRF-1 and TFAM followed the same trend of PGC-1ß. The level of mtDNA, ND1 and the activity of citrate synthase, were decreased with aging and increased following ALCAR treatment. Furthermore, ALCAR counteracted the age-related increase of deleted mtDNA. We also analyzed the content of proteins involved in mitochondrial dynamics (Drp1, Fis1, OPA1 and MNF2) and found an age-dependent increase of MFN2 and of the long form of OPA1. ALCAR treatment restored the content of the two proteins to the level of the young rats. No changes with aging and ALCAR were observed for Drp1 and Fis1. ALCAR reduced total cellular levels of oxidized PRXs and counteracted the age-related decrease of PRX3 and SOD2. Overall, our findings indicate a systemic positive effect of ALCAR dietary treatment and a tissue specific regulation of mitochondrial homeostasis in brain of old rats. Moreover, it appears that ALCAR acts as a nutrient since in most cases its effects were almost completely abolished one month after treatment suspension. Dietary supplementation of old rats with this compound seems a valuable approach to prevent age-related mitochondrial dysfunction and might ultimately represent a strategy to delay age-associated negative consequences in mitochondrial homeostasis.

Diet enrichment with a specific essential free amino acid mixture improves healing of undressed wounds in aged rats.

Chronic wounds are a major, often underestimated, health problem for the elderly. Standard wound care products are not usually manufactured to meet the increased demand of nutrients by skin cells in order to regenerate new tissue and accelerate healing. This work was therefore undertaken to establish whether wound healing could be accelerated by nutritional supplementation with a specific mixture tailored to human need of essential amino acids (EAAs) without topical medication. To this end, using a skin full-thickness excisional model in aged rats, we compared the closure dynamics of undressing wounds in animals fed an EAAs-enriched diet or standard diet. We assessed the degree of fibrosis and inflammation, as well as relevant signaling molecules such as COL1A1, iNOS and TGFß1. The results showed wound healing was accelerated in EAAs-fed rats, which was accompanied by reduced inflammation and changes in TGFß1 and COL1A1 expression. Collectively, our findings indicate that dietary supplementation with balanced EAAs diet could serve as a strategy to accelerate wound healing without inducing fibrosis and could therefore be a simple but pivotal therapeutic approach in human also.

Geriatric syndromes: How to treat.

The survival of HIV-infected persons has been increasing over the last years, thanks to the implementation of more effective pharmacological and non-pharmacological interventions. Nevertheless, HIV-infected persons are often "biologically" older than their "chronological" age due to multiple clinical, social, and behavioral conditions of risk. The detection in this population of specific biological features and syndromic conditions typical of advanced age has made the HIV infection an interesting research model of accelerated and accentuated aging. Given such commonalities, it is possible that "biologically aged" HIV-positive persons might benefit from models of adapted and integrated care developed over the years by geriatricians for the management of their frail and complex patients. In this article, possible strategies to face the increasingly prevalent geriatric syndromes in HIV-infected persons are discussed. In particular, it is explained the importance of shifting from the traditional disease-oriented approach into models of care facilitating a multidisciplinary management of frailty.

Sarcopenia in heart failure: mechanisms and therapeutic strategies.

Chronic heart failure (CHF) is a highly prevalent condition among the elderly and is associated with considerable morbidity, institutionalization and mortality. In its advanced stages, CHF is often accompanied by the loss of muscle mass and strength. Sarcopenia is a geriatric syndrome that has been actively studied in recent years due to its association with a wide range of adverse health outcomes. The goal of this review is to discuss the relationship between CHF and sarcopenia, with a focus on shared pathophysiological pathways and treatments. Malnutrition, systemic inflammation, endocrine imbalances, and oxidative stress appear to connect sarcopenia and CHF. At the muscular level, alterations of the ubiquitin proteasome system, myostatin signaling, and apoptosis have been described in both sarcopenia and CHF and could play a role in the loss of muscle mass and function. Possible therapeutic strategies to impede the progression of muscle wasting in CHF patients include protein and vitamin D supplementation, structured physical exercise, and the administration of angiotensin-converting enzyme inhibitors and ß-blockers. Hormonal supplementation with growth hormone, testosterone, and ghrelin is also discussed as a potential treatment.

The geriatric management of frailty as paradigm of "The end of the disease era".

The sustainability of healthcare systems worldwide is threatened by the absolute and relative increase in the number of older persons. The traditional models of care (largely based on a disease-centered approach) are inadequate for a clinical world dominated by older individuals with multiple (chronic) comorbidities and mutually interacting syndromes. There is the need to shift the center of the medical intervention from the disease to the biological age of the individual. Thus, multiple medical specialties have started looking with some interest at concepts of geriatric medicine in order to better face the increased complexity (due to age-related conditions) of their average patient. In this scenario, special interest has been given to frailty, a condition characterized by the reduction of the individual's homeostatic reserves and increased vulnerability to stressors. Frailty may indeed represent the fulcrum to lever for reshaping the healthcare systems in order to make them more responsive to new clinical needs. However, the dissemination of the frailty concept across medical specialties requires a parallel and careful consideration around the currently undervalued role of geriatricians in our daily practice.

Anorexia of Aging: Risk Factors, Consequences, and Potential Treatments.

Older people frequently fail to ingest adequate amount of food to meet their essential energy and nutrient requirements. Anorexia of aging, defined by decrease in appetite and/or food intake in old age, is a major contributing factor to under-nutrition and adverse health outcomes in the geriatric population. This disorder is indeed highly prevalent and is recognized as an independent predictor of morbidity and mortality in different clinical settings. Even though anorexia is not an unavoidable consequence of aging, advancing age often promotes its development through various mechanisms. Age-related changes in life-style, disease conditions, as well as social and environmental factors have the potential to directly affect dietary behaviors and nutritional status. In spite of their importance, problems related to food intake and, more generally, nutritional status are seldom attended to in clinical practice. While this may be the result of an "ageist" approach, it should be acknowledged that simple interventions, such as oral nutritional supplementation or modified diets, could meaningfully improve the health status and quality of life of older persons.

Treating sarcopenia in older and oldest old.

The presence of sarcopenia is not only rapidly rising in geriatric clinical practice and research, but is also becoming a significant concept in numerous medical specialties. This rapidly rising concept has encouraged the need to identify methods for treating sarcopenia. Physical activity measures using resistance training exercise, combined with nutritional interventions (protein and amino acid supplementation) have shown to significantly improve muscle mass and strength in older persons. Moreover, resistance training may improve muscle strength and mass by improving protein synthesis in skeletal muscle cells. Aerobic exercise has also shown to hold beneficial impacts on sarcopenia by improving insulin sensitivity. At the moment, the literature indicates that most significant improvement in sarcopenia is based on exercise programs. Thus, this type of intervention should be implemented in a persistent manner over time in elders, with or at risk of muscle loss. At the same time, physical training exercise should include correcting nutritional deficits with supplementation methods. For example, in older sarcopenic patients with adequate renal function, daily protein intake should be increased to >1. 0 grams of protein per kilogram of body weight. In particular, leucine, - hydroxy ß-methylbutyrate (HMB), creatine and some milk-based proteins have been shown to improve skeletal muscle protein balance. In addition, it is also recommended for adjustment of for vitamin D deficiency, if present, considering the crucial role of vitamin D in the skeletal muscle. In this review, we provide evidence regarding the effects of different physical exercise protocols, specific nutritional intervention, and some new metabolic agents (HMB, citrulline malate, ornithine, and others) on clinical outcomes related to sarcopenia in older adults.