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

Health-related quality of life (HRQOL) in patients on chronic hemodialysis has not improved significantly in the last 20 years. This is largely due to their substantial symptom burden which is rarely assessed and treated in routine clinical practice. This is also consequence of the lack of an appropriate armamentarium for the treatments of such symptoms. Adequate studies on the causes and pathogenesis of the symptoms of hemodialysis patients are needed followed by high-quality studies on possible therapeutic pharmacological and non-pharmacological interventions. Patients on chronic hemodialysis deserve a better quality of life.

Proteins are macro-molecules crucial for cell life, which are made up of amino acids (AAs). In healthy people, protein synthesis and degradation are well balanced. However, in the presence of hypercatabolic stimulation (i.e., inflammation), protein breakdown increases as the resulting AAs are consumed for metabolic proposes. Indeed, AAs are biochemical totipotent molecules which, when deaminated, can be transformed into energy, lipids, carbohydrates, and/or biochemical intermediates of fundamental cycles, such as the Krebs' cycle. The biochemical consequence of hyper-catabolism is protein disarrangement, clinically evident with signs such as sarcopenia, hypalbuminemia, anaemia, infection, and altered fluid compartmentation, etc. Hypercatabolic protein disarrangement (HPD) is often underestimated by clinicians, despite correlating with increased mortality, hospitalization, and morbidity quite independent of the primary disease. Simple, cheap, repeatable measurements can be used to identify HPD. Therefore, identification and treatment of proteins' metabolic impairment with appropriate measurements and therapy is a clinical strategy that could improve the prognosis of patients with acute/chronic hypercatabolic inflammatory disease. Here, we describe the metabolism of protein and AAs in hypercatabolic syndrome, illustrating the clinical impact of protein disarrangement. We also illustrate simple, cheap, repeatable, and worldwide available measurements to identify these conditions. Finally, we provide scientific evidence for HPD nutritional treatment.

The Mediterranean Diet Foundation, in collaboration with the International Menarini Foundation, organized the “International Conference on Mediterranean Diet and Health: A Lifelong Approach.” The Conference was held in Ostuni (Puglia, Italy) from March 30 to April 1, 2017. The event received the endorsement of the American Federation for Aging Research, the Research Consortium “Luigi Amaducci,” the European Nutrition for Health Alliance, the European Union Geriatric Medicine Society, the Clinical Section of the International Association of Gerontology and Geriatrics—European Region, the National Research Council Research Project on Aging, the Italian Society of Gerontology and Geriatrics, and the Italian Society of Clinical Nutrition and Metabolism. During the conference, results were presented from major studies on dietary interventions aiming to assess the efficacy of the Mediterranean diet in the prevention of chronic diseases and the potential underlying mechanisms. Twenty-six international speakers, in seven different sessions, discussed the biological basis, clinical impact, health policy, and behavioral implications of the Mediterranean diet, and its use in potential interventions for health promotion.

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Advanced age is characterized by several changes, one of which is the impairment of the homeostasis of intestinal microbiota. These alterations critically influence host health and have been associated with morbidity and mortality in older adults. "Inflammaging," an age-related chronic inflammatory process, is a common trait of several conditions, including sarcopenia. Interestingly, imbalanced intestinal microbial community has been suggested to contribute to inflammaging. Changes in gut microbiota accompanying sarcopenia may be attenuated by supplementation with pre- and probiotics. Although muscle aging has been increasingly recognized as a biomarker of aging, the pathophysiology of sarcopenia is to date only partially appreciated. Due to its development in the context of the age-related inflammatory milieu, several studies favor the hypothesis of a tight connection between sarcopenia and inflammaging. However, conclusive evidence describing the signaling pathways involved has not yet been produced. Here, we review the current knowledge of the changes in intestinal microbiota that occur in advanced age with a special emphasis on findings supporting the idea of a modulation of muscle physiology through alterations in gut microbial composition and activity.

Objective The aim of the present study was to investigate the prevalence of abnormal cholesterol levels and to explore awareness of cholesterol values in an unselected sample of community-living adults. Design Cross-sectional survey. Setting Exhibitions, malls and health promotion campaigns across Italy. Participants 3535 community dwellers aged 18-98 years were enrolled between September 2016 and June 2017. Analyses were conducted in 3040 participants, after excluding 495 enrolees on cholesterol-lowering medications. Main outcome measures Total blood cholesterol levels and awareness of cholesterol values. Results Abnormal blood cholesterol values were found in 1961 (64.5%) of participants with no differences between genders (p=0.06). Among those who believed they had normal cholesterol levels, only 48% had values below 200 mg/dL. More than 40% had cholesterol values between 200 and 240 mg/dL, and around 10% had values >240 mg/dL. More than one-third of participants had not measured cholesterol in the last year. Among them, only 36% had normal cholesterol levels. Conclusions Abnormal blood cholesterol is highly prevalent in our sample of Italian community dwellers, with less than half of participants being aware of their cholesterol levels.

Background: The ongoing “Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies (SPRINTT)” randomized controlled trial (RCT) is testing the efficacy of a multicomponent intervention in the prevention of mobility disability in older adults with physical frailty & sarcopenia (PF&S). Here, we describe the procedures followed for PF&S case finding and screening of candidate participants for the SPRINTT RCT. We also illustrate the main demographic and clinical characteristics of eligible screenees. Methods: The identification of PF&S was based on the co-occurrence of three defining elements: (1) reduced physical performance (defined as a score on the Short Physical Performance Battery between 3 and 9); (2) low muscle mass according to the criteria released by the Foundation for the National Institutes of Health; and (3) absence of mobility disability (defined as ability to complete the 400-m walk test in 15 min). SPRINTT was advertised through a variety of means. Site-specific case finding strategies were developed to accommodate the variability across centers in catchment area characteristics and access to the target population. A quick “participant profiling” questionnaire was devised to facilitate PF&S case finding. Results: During approximately 22 months, 12,358 prescreening interviews were completed in 17 SPRINTT sites resulting in 6710 clinic screening visits. Eventually, 1566 candidates were found to be eligible for participating in the SPRINTT RCT. Eligible screenees showed substantial physical function impairment and comorbidity burden. In most centers, project advertisement through mass media was the most rewarding case finding strategy. Conclusion: PF&S case finding in the community is a challenging, but feasible task. Although largely autonomous in daily life activities, older adults with PF&S suffer from significant functional impairment and comorbidity. This subset of the older population is therefo

Sarcopenia, the progressive and generalized loss of skeletal muscle mass and strength/function associated with aging, increases the risk of a vast array of adverse health outcomes, including falls, morbidity, loss of independence, disability, and mortality. As such, sarcopenia poses a huge socioeconomic burden in developed countries. The development and implementation of effective interventions against sarcopenia are therefore a public health priority. A preliminary, fundamental step in such a process entails the agreement of researchers, healthcare professionals and policy-makers around a unique operational definition of sarcopenia. This will facilitate the framing of a clear clinical entity to be incorporated in standard practice, the understanding of the underlying pathophysiology, and the identification of biological targets for drug development.

Mitochondrial structural and functional integrity is maintained through the coordination of several processes (e.g., biogenesis, dynamics, mitophagy), collectively referred to as mitochondrial quality control (MQC). Dysfunctional MQC and inflammation are hallmarks of aging and are involved in the pathogenesis of muscle wasting disorders, including sarcopenia and cachexia. One of the consequences of failing MQC is the release of mitochondria-derived damage-associated molecular patterns (DAMPs). By virtue of their bacterial ancestry, these molecules can trigger an inflammatory response by interacting with receptors similar to those involved in pathogen-associated responses. Mitochondria-derived DAMPs, especially cell-free mitochondrial DNA, have recently been associated with conditions characterized by chronic inflammation, such as aging and degenerative diseases. Yet, their actual implication in the aging process and muscle wasting disorders is at an early stage of investigation. Here, we review the contribution of mitochondria-derived DAMPs to age-related systemic inflammation. We also provide arguments in support of the exploitation of such signaling pathways for the management of muscle wasting conditions.

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

Sarcopenia, the progressive and generalized loss of muscle mass and strength/function, is a major health issue in older adults, given its high prevalence and burdensome clinical ramifications. The absence of a unified operational definition for sarcopenia has hampered its full appreciation by healthcare providers, researchers and policy-makers. At the same time, this unresolved debate and the complexity of musculoskeletal aging pose major challenges to the identification of clinically meaningful biomarkers. This review summarizes the current knowledge on biological markers for sarcopenia, including a critical appraisal of traditional procedures for biomarker development in the field of muscle aging. As an alternative approach, we illustrate the potential advantages of biomarker discovery procedures based on multivariate methodologies. Relevant examples of multidimensional biomarker modeling are provided with an emphasis on its clinical and research application.

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

Objective: Inadequate protein intake can impair protein balance thus leading to skeletal muscle atrophy, impaired body growth, and functional decline. Foods provide both non-essential (NEAAs) and essential amino acids (EAAs) that may convey different metabolic stimuli to specific organs and tissues. In this study, we sought to evaluate the impact of six diets, with various EAA/NEAA blends, on body composition and the risk of developing tissue wasting in late middle-aged male mice. Methods: Six groups of late middle-aged male mice were fed for 35 days with iso-nutrients, iso-caloric, and iso-nitrogenous special diets containing different EAA/NEAA ratios ranging from 100/0% to 0/100%. One group fed with standard laboratory rodent diet (StD) served as control. Preliminarily, we verified the palatability of the diets by recording the mice preference, and by making accessible all diets simultaneously, in comparison to StD. Body weight, food and water consumption were measured every 3 days. Blood and urine samples, as well as heart, kidneys, liver, spleen, triceps surae, retroperitoneal WAT, and BAT were harvested and weighed. Results: Mice consuming NEAA-based diets, although showing increased food and calorie intake, suffered the most severe weight loss. Interestingly, the diet containing a EAA/NEAA-imbalance, with moderate NEAAs prevalence, was able to induce catabolic stimuli, generalized body wasting, and systemic metabolic alterations comparable to those observed with diet containing NEAA alone. In addition, complete depletion of retroperitoneal white adipose tissue and a severe loss (> 75%) of brown adipose tissue were observed together with muscle wasting. Conversely, EAA-containing diets induced significant decreases in body weight by reducing primarily fat reserves, but at the same time they improved the clinical parameters. On these basis we can deduce that tissue wasting was caused by altered AA quality, independent of reduced nitrogen or caloric intake. Co

In recent years, an extensive body of literature focused on the gut-brain axis and the possible role played by the gut microbiota in modulating brain morphology and function from birth to old age. Gut microbiota has been proposed as a relevant player during the early phases of neurodevelopment, with possible long-standing effects in later life. The reduction in gut microbiota diversity has also become one of the hallmarks of aging, and disturbances in its composition are associated with several (age-related) neurological conditions, including depression, Alzheimer's disease, and Parkinson's disease. Several pathways have been evoked for gut microbiota-brain communication, including neural connections (vagus nerve), circulating mediators derived by host-bacteria cometabolism, as well as the influence exerted by gut microbiota on host gut function, metabolism, and immune system. Although the most provoking data emerged from animal studies and despite the huge debate around the possible epiphenomenal nature of those findings, the gut microbiota-brain axis still remains a fascinating target to be exploited to attenuate some of the most burdensome consequences of aging.

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Sarcopenia, the progressive and generalised loss of muscle mass and strength/function, is a major health issue in older adults given its high prevalence and burdensome clinical implications. Over the years, this condition has been endorsed as a marker for discriminating biological from chronological age. However, the absence of a unified operational definition has hampered its full appreciation by healthcare providers, researchers and policy-makers. In addition to this unsolved debate, the complexity of musculoskeletal ageing represents a major challenge to the identification of clinically meaningful biomarkers. Here, we illustrate the advantages of biomarker discovery procedures in muscle ageing based on multivariate methodologies as an alternative approach to traditional single-marker strategies. The rationale, design and methods of the “BIOmarkers associated with Sarcopenia and PHysical frailty in EldeRly pErsons” (BIOSPHERE) study are described as an application of a multi-marker strategy for the development of biomarkers for the newly operationalised Physical Frailty & Sarcopenia condition.

The present study was undertaken to provide a better insight into the relationship between different levels of body mass index (BMI) and changing risk for hypertension, using an unselected sample of participants assessed during the Longevity Check-up 7+ (Lookup 7+) project. Lookup 7+ is an ongoing cross-sectional survey started in June 2015 and conducted in unconventional settings (i.e., exhibitions, malls, and health promotion campaigns) across Italy. Candidate participants are eligible for enrolment if they are at least 18 years of age and provide written informed consent. Specific health metrics are assessed through a brief questionnaire and direct measurement of standing height, body weight, blood glucose, total blood cholesterol, and blood pressure. The present analyses were conducted in 7907 community-living adults. According to the BMI cutoffs recommended by the World Health Organization, overweight status was observed among 2896 (38%) participants; the obesity status was identified in 1135 participants (15%), with 893 (11.8%) participants in class I, 186 (2.5%) in class II, and 56 (0.7%) in class III. Among enrollees with a normal BMI, the prevalence of hypertension was 45% compared with 67% among overweight participants, 79% in obesity class I and II, and up to 87% among participants with obesity class III (p for trend < 0.001). After adjusting for age, significantly different distributions of systolic and diastolic blood pressure across BMI levels were consistent. Overall, the average systolic blood pressure and diastolic blood pressure increased significantly and linearly across BMI levels. In conclusion, we found a gradient of increasing blood pressure with higher levels of BMI. The fact that this gradient is present even in the fully adjusted analyses suggests that BMI may cause a direct effect on blood pressure, independent of other clinical risk factors.

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

Mitochondrial dysfunction is a relevant mechanism in cardiac aging. Here, we investigated the effects of late-life enalapril administration at a non-antihypertensive dose on mitochondrial genomic stability, oxidative damage, and mitochondrial quality control (MQC) signaling in the hearts of aged rats. The protein expression of selected mediators (i.e., mitochondrial antioxidant enzymes, energy metabolism, mitochondrial biogenesis, dynamics, and autophagy) was measured in old rats randomly assigned to receive enalapril (n = 8) or placebo (n = 8) from 24 to 27 months of age. We also assessed mitochondrial DNA (mtDNA) content, citrate synthase activity, oxidative lesions to protein and mtDNA (i.e., carbonyls and the abundance of mtDNA 4834 deletion), and the mitochondrial transcription factor A (TFAM) binding to specific mtDNA regions. Enalapril attenuated cardiac hypertrophy and oxidative stress-derived damage (mtDNA oxidation, mtDNA 4834 deletion, and protein carbonylation), while increasing mitochondrial antioxidant defenses. The binding of mitochondrial transcription factor A to mtDNA regions involved in replication and deletion generation was enhanced following enalapril administration. Increased mitochondrial mass as well as mitochondriogenesis and autophagy signaling were found in enalapril-treated rats. Late-life enalapril administration mitigates age-dependent cardiac hypertrophy and oxidative damage, while increasing mitochondrial mass and modulating MQC signaling. Further analyses are needed to conclusively establish whether enalapril may offer cardioprotection during aging.

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Among the complex determinants of aging, mitochondrial dysfunction has been in the spotlight for a long time. As the hub for many cellular functions, the maintenance of an adequate pool of functional mitochondria is crucial for tissue homeostasis. Their unique role in energy supply makes these organelles essential, especially in those tissues strictly dependent on oxidative metabolism. Mitochondrial quality control (MQC) is ensured by pathways related to protein folding and degradation as well as by processes involving the entire organelle, such as biogenesis, dynamics, and mitophagy. Dysfunctional MQC, oxidative stress and inflammation are hallmarks of senescence and chronic degenerative diseases. One of the consequences of age-related failing MQC and oxidative stress is the release of mitochondria-derived damage-associated molecular patterns (DAMPs). Through their bacterial ancestry, these molecules contribute to mounting an inflammatory response by interacting with receptors similar to those involved in pathogen-associated responses. Mitochondrial DAMPs, especially cell-free mitochondrial DNA, have recently become the subject of intensive research because of their possible involvement in conditions associated with inflammation, such as aging and degenerative diseases. Here, we review the contribution of mitochondrial DAMPs to inflammation and discuss some of the mechanisms at the basis of their generation.

Osteoporosis is a condition featured by bone mass loss and bone tissue microarchitectural alterations due to impaired tissue homeostasis favoring excessive bone resorption versus deposition. The trigger of such an impairment and the downstream molecular pathways involved are yet to be clarified. The natural course of osteoporosis is particularly worrisome because, through a “silent” progression, it enhances bone fragility, increases the risk of fractures and is associated with increased risk of disability and mortality. To date, the assessment of bone mineral density by dual-energy X-ray absorptiometry, represents the non-invasive gold standard for the evaluation of bone mineralization and the diagnosis of osteoporosis. Although long known as a condition merely related to the hormonal-driven loss of bone homeostasis, emerging evidence supports the need of reframing osteoporosis in the context of structural and functional changes of the musculoskeletal system as a whole. Several age-related alterations of bone microenvironment and an altered bone-muscle crosstalk have been suggested to be relevant contributors to loss of bone strength and mass characterizing osteoporosis. The present work provides an overview of the current knowledge of the pathophysiology of osteoporosis obtained through advances in epigenetics, cell biology and osteoimmunology. In light of the increasingly recognized importance of bone-muscle interconnection, this review also discusses relevant pathways that may be dissected for identifying new therapeutic targets for age-related musculoskeletal degeneration.

The sustainability of health and social care systems is threatened by a growing population of older persons with heterogeneous needs related to multimorbidity, frailty, and increased risk of functional impairment. Since disability is difficult to reverse in old age and is extremely burdensome for individuals and society, novel strategies should be devised to preserve adequate levels of function and independence in late life. The development of mobility disability, an early event in the disablement process, precedes and predicts more severe forms of inability. Its prevention is, therefore, critical to impede the transition to overt disability. For this reason, the Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies (SPRINTT) project is conducting a randomized controlled trial (RCT) to test a multicomponent intervention (MCI) specifically designed to prevent mobility disability in high-risk older persons. SPRINTT is a phase III, multicenter RCT aimed at comparing the efficacy of a MCI, based on long-term structured physical activity, nutritional counseling/dietary intervention, and an information and communication technology intervention, versus a healthy aging lifestyle education program designed to prevent mobility disability in 1500 older persons with physical frailty and sarcopenia who will be followed for up to 36 months. The primary outcome of the SPRINTT trial is mobility disability, operationalized as the inability to walk for 400 m within 15 min, without sitting, help of another person, or the use of a walker. Secondary outcomes include changes in muscle mass and strength, persistent mobility disability, falls and injurious falls, disability in activities of daily living, nutritional status, cognition, mood, the use of healthcare resources, cost-effectiveness analysis, quality of life, and mortality rate. SPRINTT results are expected to promote significant advancements in the management of frail older persons a

In the present article, the rationale that guided the operationalization of the theoretical concept of physical frailty and sarcopenia (PF&S), the condition of interest for the “Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies” (SPRINTT) trial, is presented. In particular, the decisions lead to the choice of the adopted instruments, and the reasons for setting the relevant thresholds are explained. In SPRINTT, the concept of physical frailty is translated with a Short Physical Performance Battery score of ≥3 and ≤9. Concurrently, sarcopenia is defined according to the recent definitions of low muscle mass proposed by the Foundation for the National Institutes of Health—Sarcopenia Project. Given the preventive purpose of SPRINTT, older persons with mobility disability (operationalized as incapacity to complete a 400-m walk test within 15 min; primary outcome of the trial) at the baseline are not included within the diagnostic spectrum of PF&S.

The identification of cost-effective interventions that improve the health status and prevent disability in old age is one of the most important public health challenges. Regular physical activity is the only intervention that has consistently been shown to improve functional health and energy balance and to reduce the risk of cardiovascular disease, stroke, diabetes, several cancers, depression and falls. In advanced age, physical activity is also effective at mitigating sarcopenia, restoring robustness, and preventing/delaying the development of disability. On the other hand, physical inactivity is recognized as one of the leading causes of several chronic degenerative diseases and is also a major contributing factor to sarcopenia and functional disability. This compelling evidence has prompted the World Health Organization to recommend engaging in regular physical activity throughout one’s life course. The present review summarizes the available evidence in support of physical activity as a remedy against physical frailty and sarcopenia. The relevant pathways through which the benefits of physical activity are conveyed are also discussed.

Frailty is a clinical state characterized by a decrease of an individual's homeostatic reserves and is responsible for enhanced vulnerability to endogenous and/or exogenous stressors. Such a condition of extreme vulnerability exposes individuals to an increased risk of negative health-related outcomes. Multiple operational definitions of frailty are available in the literature, but none can be indicated as a gold standard. Frailty should be considered a condition of major interest for public health and become the lever for reshaping the obsolete health care systems currently unable to adequately address the clinical needs of aging populations.

Sarcopenia, the age-dependent loss of muscle mass and function, is a common condition among older adults, and is associated with several adverse health outcomes. Owing to the impact of sarcopenia on quality of life, disability and mortality, a greater awareness is necessary in order to correctly identify the condition both in community and geriatric settings. Research on sarcopenia prevention and treatment is developing quickly, but many questions are still unanswered. The core of the sarcopenia condition involves quantitative and qualitative losses of skeletal muscle. These two dimensions should therefore be considered when designing and testing preventive and therapeutic interventions. The recently released operationalization of sarcopenia by the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project allows for the framing of an objective, standardized, and clinically relevant condition, which should facilitate its translation into the clinical arena as well as its adoption by public health and regulatory agencies. Such a conceptualization might eventually encourage key stakeholders to combine their efforts in approaching the sarcopenia condition. Bearing these considerations in mind, the “Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies” project has operationalized a specific condition, named physical frailty and sarcopenia (PF&S), characterized by the combination of low physical performance (based on the Short Physical Performance Battery) and low muscle mass (according to the FNIH cut-points). A randomized controlled trial will be conducted to evaluate the efficacy of a multi-component intervention for preventing mobility disability and other adverse health outcomes in older adults with PF&S.

Physical frailty (PF) and sarcopenia are major health issues in geriatric populations, given their high prevalence and association with several adverse outcomes. Nevertheless, the lack of an univocal operational definition for the two conditions has so far hampered their clinical implementation. Existing definitional ambiguities of PF and sarcopenia, together with their complex underlying pathophysiology, also account for the absence of robust biomarkers that can be used for screening, diagnostic and/or prognostication purposes. This review provides an overview of currently available biological markers for PF and sarcopenia, as well as a critical appraisal of strengths and weaknesses of traditional procedures for biomarker development in the field. A novel approach for biomarker identification and validation, based on multivariate methodologies, is also discussed. This strategy relies on the multidimensional modeling of complementary biomarkers to cope with the phenotypical and pathophysiological complexity of PF and sarcopenia. Biomarkers identified through the implementation of multivariate strategies may be used to support the detection of the two conditions, track their progression over time or in response to interventions, and reveal the onset of complications (e.g., mobility disability) at a very early stage.

The exploration of frailty as a pre-disability geriatric condition represents one of the most promising research arenas of modern medicine. Frailty is today indicated as a paradigmatic condition around which the traditional healthcare systems might be re-shaped and optimized in order to address the complexities and peculiarities of elders. Unfortunately, the lack of consensus around a single operational definition has limited the clinical implementation of frailty in clinical practice. In these last years, growing attention (even beyond the traditional boundaries of geriatric medicine) has been given to physical performance measures. These instruments have shown to be predictive of negative health-related events and able to support an accurate estimation of the “biological age” in late life. The strong construct of physical performance measures also makes them particularly suitable for the assessment of the frailty status. Furthermore, the adoption of physical performance measures may help render the frailty condition more organ-specific (i.e., centred on the skeletal muscle quality) and less heterogeneous than currently perceived. The translation of the frailty concept by means of physical performance measures implicitly represents an attempt to go beyond traditional paradigms. In this context, the recently funded “Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies” (SPRINTT) project (largely based on such a novel approach) may indeed fill an important gap in the field and provide key insights for counteracting the disabling cascade in the elderly.

Sarcopenia, the age-dependent loss of muscle mass and function/strength, is increasingly recognized as a major risk factor for adverse outcomes in frail older people. As such, the skeletal muscle is a relevant target for interventions aimed at preventing or postponing the occurrence of negative health-related events in late life. The association among physical inactivity, insufficient intake of energy and protein, and poor muscle health in older adults suggests that physical exercise and targeted nutritional supplementation may offer substantial therapeutic gain against sarcopenia and its negative correlates. This view is supported by observational studies as well as by small-scale clinical trials. In this review, we summarize the available evidence on the beneficial effects of behavioral interventions on sarcopenia. We also briefly describe how the knowledge gathered so far has been used to design the "Sarcopenia and Physical fRailty IN older people: multicomponenT Treatment strategies" (SPRINTT) project. The randomized clinical trial conducted within SPRINTT will provide robust evidence on the effectiveness of exercise and nutrition at preventing negative outcomes associated with sarcopenia and physical frailty.

Older people often experience loss of appetite and/or decreased food intake that, unavoidably, impact energy metabolism and overall health status. The association of age-related nutritional deficits with several adverse outcomes has led to the recognition of a geriatric condition referred to as “anorexia of aging.” Anorexia is an independent predictor of morbidity and mortality both in the community and across clinical settings. Multidimensional interventions within personalized care plans currently represent the most effective option to ensure the provision of adequate amounts of food, limit weight loss, and prevent adverse health outcomes in older adults.

Sarcopenia encompasses the loss of muscle mass and strength/function during aging. Several methods are available for the estimation of muscle or lean body mass. Popular assessment tools include body imaging techniques (e.g., magnetic resonance imaging, computed tomography, dual X-ray absorptiometry, ultrasonography), bioelectric impedance analysis, anthropometric parameters (e.g., calf circumference, mid-arm muscle circumference), and biochemical markers (total or partial body potassium, serum and urinary creatinine, deuterated creatine dilution method). The heterogeneity of the populations to be evaluated as well as the setting in which sarcopenia is investigated impacts the definition of “gold standard” assessment techniques. The aim of this article is to critically review available methods for muscle mass estimation, highlighting strengths and weaknesses of each of them as well as their proposed field of application.

Background: Chronic inflammation, changes in body composition, and declining physical function are hallmarks of the ageing process. The aim of the present study was to provide a preliminary characterisation of the relationship among these age-related phenomena via multivariate modelling. Methods: Thirty-five old adults (OAs) and 17 young adults (YAs) were enrolled. The volume of skeletal muscle, subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) of the thigh was quantified by three-dimensional magnetic resonance imaging. Muscle strength was measured by knee extension strength testing. In OAs, physical performance was further assessed via the Short Physical Performance Battery (SPPB). Multi-block partial least squares-discriminant analysis (PLS-DA) was employed to explore the relationship among inflammatory profiles and functional and imaging parameters. Double cross-validation procedures were used to validate the predictive ability of the PLS-DA model. Results: The optimal complexity of the PLS-DA model was found to be two latent variables. The proportion of correct classification was 92.3% in calibration (94.1% in YAs and 91.4% in OAs), 84.6% in internal validation (95.3% in YAs and 78.5% in OAs), and 82.6% in external validation (94% in YAs and 76.9% in OAs). Relative to YAs, OAs were characterised by smaller muscle volume, greater IMAT volume, lower muscle strength, and higher levels of myeloperoxidase, P-selectin, soluble intercellular adhesion molecule 1, and vascular cell adhesion molecule 1. Compared with OAs with SPPB >8, those scoring ≤8 were characterised by smaller muscle volume, greater SAT volume, lower muscle strength, and higher levels of interleukin 1 beta, 6, 10, 12, 13, tumour necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor. Conclusions: Multi-block PLS-DA identified distinct patterns of relationships among circulating cytokines and functional and imaging parameters in persons of different ages

Sarcopenia, the age-related loss of muscle mass and function, imposes a dramatic burden on individuals and society. The development of preventive and therapeutic strategies against sarcopenia is therefore perceived as an urgent need by health professionals and has instigated intensive research on the pathophysiology of this syndrome. The pathogenesis of sarcopenia is multifaceted and encompasses lifestyle habits, systemic factors (e.g., chronic inflammation and hormonal alterations), local environment perturbations (e.g., vascular dysfunction), and intramuscular specific processes. In this scenario, derangements in skeletal myocyte mitochondrial function are recognized as major factors contributing to the age-dependent muscle degeneration. In this review, we summarize prominent findings and controversial issues on the contribution of specific mitochondrial processes - including oxidative stress, quality control mechanisms and apoptotic signaling - on the development of sarcopenia. Extramuscular alterations accompanying the aging process with a potential impact on myocyte mitochondrial function are also discussed. We conclude with presenting methodological and safety considerations for the design of clinical trials targeting mitochondrial dysfunction to treat sarcopenia. Special emphasis is placed on the importance of monitoring the effects of an intervention on muscle mitochondrial function and identifying the optimal target population for the trial. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting. © 2013 Elsevier Ltd. All rights reserved.

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