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Our results suggest that in patients with cirrhosis and NAFLD the gut microbiota profile and systemic inflammation are significantly correlated and can concur in the process of hepatocarcinogenesis. (Hepatology 2018).

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.

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.

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.

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

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.

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