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1.
An Integrated Approach to Skeletal Muscle Health in Aging.
Agostini, D, Gervasi, M, Ferrini, F, Bartolacci, A, Stranieri, A, Piccoli, G, Barbieri, E, Sestili, P, Patti, A, Stocchi, V, et al
Nutrients. 2023;(8)
Abstract
A decline in muscle mass and function represents one of the most problematic changes associated with aging, and has dramatic effects on autonomy and quality of life. Several factors contribute to the inexorable process of sarcopenia, such as mitochondrial and autophagy dysfunction, and the lack of regeneration capacity of satellite cells. The physiologic decline in muscle mass and in motoneuron functionality associated with aging is exacerbated by the sedentary lifestyle that accompanies elderly people. Regular physical activity is beneficial to most people, but the elderly need well-designed and carefully administered training programs that improve muscle mass and, consequently, both functional ability and quality of life. Aging also causes alteration in the gut microbiota composition associated with sarcopenia, and some advances in research have elucidated that interventions via the gut microbiota-muscle axis have the potential to ameliorate the sarcopenic phenotype. Several mechanisms are involved in vitamin D muscle atrophy protection, as demonstrated by the decreased muscular function related to vitamin D deficiency. Malnutrition, chronic inflammation, vitamin deficiencies, and an imbalance in the muscle-gut axis are just a few of the factors that can lead to sarcopenia. Supplementing the diet with antioxidants, polyunsaturated fatty acids, vitamins, probiotics, prebiotics, proteins, kefir, and short-chain fatty acids could be potential nutritional therapies against sarcopenia. Finally, a personalized integrated strategy to counteract sarcopenia and maintain the health of skeletal muscles is suggested in this review.
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2.
Movement and health beyond care, MoviS: study protocol for a randomized clinical trial on nutrition and exercise educational programs for breast cancer survivors.
Natalucci, V, Ferri Marini, C, De Santi, M, Annibalini, G, Lucertini, F, Vallorani, L, Panico, AR, Sisti, D, Saltarelli, R, Donati Zeppa, S, et al
Trials. 2023;(1):134
Abstract
BACKGROUND Breast cancer (BC) is the most common invasive cancer in women, and exercise can significantly improve the outcomes of BC survivors. MoviS (Movement and Health Beyond Care) is a randomized controlled trial aimed to evaluate the potential health benefits of exercise and proper nutritional habits. This study aims to assess the efficacy of aerobic exercise training in improving quality of life (QoL) and health-related factors in high-risk BC. METHODS One hundred seventy-two BC survivor women, aged 30-70 years, non-metastatic, stage 0-III, non-physically active, 6-12 months post-surgery, and post chemo- or radiotherapy, will be recruited in this study. Women will be randomly allocated to the intervention arm (lifestyle recommendations and MoviS Training) or control arm (lifestyle recommendations). The MoviS training consists of 12 weeks of aerobic exercise training (2 days/week of supervised and 1 day/week of unsupervised exercise) with a progressive increase in exercise intensity (40-70% of heart rate reserve) and duration (20-60 min). Both arms will receive counseling on healthy lifestyle habits (nutrition and exercise) based on the World Cancer Research Fund International (WCRF) 2018 guidelines. The primary outcome is the improvement of the QoL. The secondary outcomes are improvement of health-related parameters such as Mediterranean diet adherence, physical activity level, flexibility, muscular fitness, fatigue, cardiorespiratory fitness (estimated maximal oxygen uptake), echocardiographic parameters, heart rate variability (average of the standard deviations of all 5 min normal to normal intervals (ASDNN/5 min) and 24 h very low and low frequency), and metabolic, endocrine, and inflammatory serum biomarkers (glycemia, insulin resistance, progesterone, testosterone, and high-sensitivity C-reactive protein). DISCUSSION This trial aims to evaluate if supervised exercise may improve QoL and health-related factors of BC survivors with a high risk of recurrence. Findings from this project could provide knowledge improvement in the field of exercise oncology through the participation of a multidisciplinary team that will provide a coordinated program of cancer care to improve healthcare quality, improve prognosis, increase survival times and QoL, and reduce the risk of BC recurrence. TRIAL REGISTRATION ClinicalTrials.gov NCT04818359 . Retrospectively registered on March 26, 2021.
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3.
Interventions on Gut Microbiota for Healthy Aging.
Donati Zeppa, S, Agostini, D, Ferrini, F, Gervasi, M, Barbieri, E, Bartolacci, A, Piccoli, G, Saltarelli, R, Sestili, P, Stocchi, V
Cells. 2022;(1)
Abstract
In recent years, the improvement in health and social conditions has led to an increase in the average lifespan. Since aging is the most important risk factor for the majority of chronic human diseases, the development of therapies and intervention to stop, lessen or even reverse various age-related morbidities is an important target to ameliorate the quality of life of the elderly. The gut microbiota, that is, the complex ecosystem of microorganisms living in the gastrointestinal tract, plays an important role, not yet fully understood, in maintaining the host's health and homeostasis, influencing metabolic, oxidative and cognitive status; for this reason, it is also named "the forgotten endocrine organ" or "the second brain". On the other hand, the gut microbiota diversity and richness are affected by unmodifiable factors, such as aging and sex, and modifiable ones, such as diet, pharmacological therapies and lifestyle. In this review, we discuss the changes, mostly disadvantageous, for human health, induced by aging, in microbiota composition and the effects of dietary intervention, of supplementation with probiotics, prebiotics, synbiotics, psychobiotics and antioxidants and of physical exercise. The development of an integrated strategy to implement microbiota health will help in the goal of healthy aging.
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4.
Nutraceuticals and Physical Activity as Antidepressants: The Central Role of the Gut Microbiota.
Donati Zeppa, S, Ferrini, F, Agostini, D, Amatori, S, Barbieri, E, Piccoli, G, Sestili, P, Stocchi, V
Antioxidants (Basel, Switzerland). 2022;(2)
Abstract
Major depressive disorder (MDD) is a common mental illness. Evidence suggests that the gut microbiota play an essential role in regulating brain functions and the pathogenesis of neuropsychiatric diseases, including MDD. There are numerous mechanisms through which the gut microbiota and brain can exchange information in a continuous, bidirectional communication. Current research emphasizes the interexchange of signals influenced by the gut microbiota that are detected and transduced in information from the gut to the nervous system involving neural, endocrine, and inflammatory mechanisms, suggesting a relationship between oxidative stress and the pathophysiology of MDD via the hyperactivation of inflammatory responses. Potential sources of inflammation in the plasma and hippocampus of depressed individuals could stem from increases in intestinal permeability. Some nutraceuticals, such as specific probiotics, namely psychobiotics, polyphenols, carotenoids, butyrate, and prebiotics, have been demonstrated to exert an antidepressant activity, but most of them need to be metabolized and activated by gut microorganisms. By inducing changes in the gut microbiota composition, physical exercise might also exert a role in alleviating depression-like symptoms. The mutual relationships among nutraceuticals, exercise, and depression will be discussed, and the potential role of the gut microbiota as a therapeutic target to treat depression will be explored.
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5.
High-intensity Interval Training Promotes the Shift to a Health-Supporting Dietary Pattern in Young Adults.
Donati Zeppa, S, Sisti, D, Amatori, S, Gervasi, M, Agostini, D, Piccoli, G, Bertuccioli, A, Rocchi, MBL, Stocchi, V, Sestili, P
Nutrients. 2020;(3)
Abstract
A healthy lifestyle is based on a correct diet and regular exercise. Little is known about the effect of different types of exercise on dietary preferences. To address the question of whether high-intensity interval training (HIIT) could modulate spontaneous food choices, an experimental study was carried out on 32 young, healthy normal-weight subjects. The spontaneous diet of each subject has been monitored over nine weeks of indoor-cycling training, divided into three mesocycles with an incremental pattern: total energy intake, macronutrients and micronutrients have been analysed. A two-way mixed model has been used to assess differences in dietary variables; a principal factor analysis has been performed to identify sample subgroups. An increased energy intake (+17.8% at T3; p < 0.01) has been observed, although macronutrients' proportions did not vary over time, without differences between sexes. An increase of free fat mass was found in the last mesocycle (+3.8%), without an augmentation of body weight, when, despite the increased training load, a stabilization of energy intake occurred. Three different subgroups characterized by different dietary modifications could be identified among participants that showed a common trend towards a healthier diet. Nine weeks of HIIT promoted a spontaneous modulation of food choices and regulation of dietary intake in young normal-weight subjects aged 21-24. Importantly, this life-period is critical to lay the foundation of correct lifestyles to prevent metabolic diseases and secure a healthy future with advancing age.
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6.
Effects of a commercially available branched-chain amino acid-alanine-carbohydrate-based sports supplement on perceived exertion and performance in high intensity endurance cycling tests.
Gervasi, M, Sisti, D, Amatori, S, Donati Zeppa, S, Annibalini, G, Piccoli, G, Vallorani, L, Benelli, P, Rocchi, MBL, Barbieri, E, et al
Journal of the International Society of Sports Nutrition. 2020;(1):6
Abstract
BACKGROUND Sports nutritional supplements containing branched-chain amino acids (BCAA) have been widely reported to improve psychological and biological aspects connected to central fatigue and performance in endurance exercise, although the topic is still open to debate. The aim of the present study was to determine whether the intake of a commercially available BCAA-based supplement, taken according to the manufacturer's recommendations, could affect the rating of perceived exertion (RPE) and performance indexes at the beginning (1d) and end of a 9-week (9w) scheduled high intensity interval training program, with an experimental approach integrating the determination of psychometric, performance, metabolic and blood biochemical parameters. METHODS This was a randomized double-blind placebo-controlled study. Thirty-two untrained, healthy young adults (20 males and 12 female) were enrolled. A high-intensity endurance cycling (HIEC) test was used to induce fatigue in the participants: HIEC consisted in ten 90 s sprints interspersed by ten 3 min recovery phases and followed by a final step time to exhaustion was used. In parallel with RPE, haematological values (creatine kinase, alanine, BCAA, tryptophan, ammonia and glucose levels), and performance indexes (maximal oxygen consumption - VO2max, power associated with lactate thresholds - WLT1, WLT2 and time to exhaustion - TTE) were assessed. All subject took the supplement (13.2 g of carbohydrates; 3.2 g of BCAA and 1.6 g of L-alanine per dose) or placebo before each test and training session. Dietary habits and training load were monitored during the entire training period. RESULTS The administration of the supplement (SU) at 1d reduced RPE by 9% during the recovery phase, as compared to the placebo (PL); at 9w the RPE scores were reduced by 13 and 21% during the sprint and recovery phase, respectively; at 9w, prolonged supplement intake also improved TTE and TRIMP. SU intake invariably promoted a rapid increase (within 1 h) of BCAA serum blood levels and prevented the post-HIEC tryptophan: BCAA ratio increase found in the PL group, at both 1d and 9w. There was no difference in dietary habits between groups and those habits did not change over time; no difference in glycemia was found between SU and PL. VO2max, WLT1 and WLT2 values improved over time, but were unaffected by supplement intake. CONCLUSIONS On the whole, these results suggest that i) the intake of the BCAA-based commercially available supplement used in this study reduces RPE as a likely consequence of an improvement in the serum tryptophan: BCAA ratio; ii) over time, reduced RPE allows subjects to sustain higher workloads, leading to increased TRIMP and TTE.
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7.
Small extracellular vesicles deliver miR-21 and miR-217 as pro-senescence effectors to endothelial cells.
Mensà, E, Guescini, M, Giuliani, A, Bacalini, MG, Ramini, D, Corleone, G, Ferracin, M, Fulgenzi, G, Graciotti, L, Prattichizzo, F, et al
Journal of extracellular vesicles. 2020;(1):1725285
Abstract
The role of epigenetics in endothelial cell senescence is a cutting-edge topic in ageing research. However, little is known of the relative contribution to pro-senescence signal propagation provided by microRNAs shuttled by extracellular vesicles (EVs) released from senescent cells. Analysis of microRNA and DNA methylation profiles in non-senescent (control) and senescent (SEN) human umbilical vein endothelial cells (HUVECs), and microRNA profiling of their cognate small EVs (sEVs) and large EVs demonstrated that SEN cells released a significantly greater sEV number than control cells. sEVs were enriched in miR-21-5p and miR-217, which target DNMT1 and SIRT1. Treatment of control cells with SEN sEVs induced a miR-21/miR-217-related impairment of DNMT1-SIRT1 expression, the reduction of proliferation markers, the acquisition of a senescent phenotype and a partial demethylation of the locus encoding for miR-21. MicroRNA profiling of sEVs from plasma of healthy subjects aged 40-100 years showed an inverse U-shaped age-related trend for miR-21-5p, consistent with senescence-associated biomarker profiles. Our findings suggest that miR-21-5p/miR-217 carried by SEN sEVs spread pro-senescence signals, affecting DNA methylation and cell replication.
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8.
Discontinuously supervised aerobic training vs. physical activity promotion in the self-management of type 2 diabetes in older Italian patients: design and methods of the 'TRIPL-A' randomized controlled trial.
Lucertini, F, Ferri Marini, C, Sisti, D, Stocchi, V, Federici, A, Gregorio, F, Piangerelli, D, Chiatti, C, Cherubini, A, Boemi, M, et al
BMC geriatrics. 2019;(1):11
Abstract
BACKGROUND Physical activity (PA) has health benefits for people with type 2 diabetes (T2D). Indeed, regular PA is considered an important part of any T2D management plan, yet most patients adopt a sedentary lifestyle. Exercise referral schemes (ERS) have the potential to effectively promote physical activity among T2D patients, and their effectiveness may be enhanced when they are supported by computer-based technologies. The 'TRIPL-A' study (i.e., a TRIal to promote PhysicaL Activity among patients in the young-old age affected by T2D) aims to assess if realizing an innovative ERS, based on a strong partnership among general practitioners, specialist physicians, exercise specialists, and patients, and supported by a web-based application (WBA), can effectively lead sedentary older T2D patients to adopt an active lifestyle. METHODS A randomized controlled design will be used, and an ERS, supported by a WBA, will be implemented. 300 physically inactive T2D patients (aged 65-74 years) will be assigned to either an intervention or control arm. Control arm patients will only receive behavioral counseling on physical activity and diet, while intervention arm patients will also undergo an 18-month (3 day/week), discontinuously supervised aerobic exercise training program. The trial will be divided into six three-month periods: during first, third and fifth period, an exercise specialist will supervise the training sessions and, using the WBA, prescribe exercise progression and monitor exercise adherence. Patients will exercise on their own in the other periods. Patients' sedentary behaviors (primary outcome), PA level, fitness status, metabolic profile, psychological well-being, quality of life, and use of health care services (secondary outcomes) will be assessed at baseline and at 6, 12, and 18 months from baseline. Repeated measure ANCOVAs will be used to compare the intervention and control arm with respect to each study outcome measure. DISCUSSION Primary and secondary outcome results will allow us to evaluate the effectiveness of an ERS, specifically designed for the management of T2D clinical conditions and supported by a WBA, in promoting PA within Italian primary care settings. TRIAL REGISTRATION This trial is retrospectively registered under the Australian New Zealand Clinical Trials Registry (reference number: ACTRN12618001164280 ; registered 13 July 2018).
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9.
Mutual Interactions among Exercise, Sport Supplements and Microbiota.
Donati Zeppa, S, Agostini, D, Gervasi, M, Annibalini, G, Amatori, S, Ferrini, F, Sisti, D, Piccoli, G, Barbieri, E, Sestili, P, et al
Nutrients. 2019;12(1)
Abstract
The adult gut microbiota contains trillions of microorganisms of thousands of different species. Only one third of gut microbiota are common to most people; the rest are specific and contribute to enhancing genetic variation. Gut microorganisms significantly affect host nutrition, metabolic function, immune system, and redox levels, and may be modulated by several environmental conditions, including physical activity and exercise. Microbiota also act like an endocrine organ and is sensitive to the homeostatic and physiological changes associated with training; in turn, exercise has been demonstrated to increase microbiota diversity, consequently improving the metabolic profile and immunological responses. On the other side, adaptation to exercise might be influenced by the individual gut microbiota that regulates the energetic balance and participates to the control of inflammatory, redox, and hydration status. Intense endurance exercise causes physiological and biochemical demands, and requires adequate measures to counteract oxidative stress, intestinal permeability, electrolyte imbalance, glycogen depletion, frequent upper respiratory tract infections, systemic inflammation and immune responses. Microbiota could be an important tool to improve overall general health, performance, and energy availability while controlling inflammation and redox levels in endurance athletes. The relationship among gut microbiota, general health, training adaptation and performance, along with a focus on sport supplements which are known to exert some influence on the microbiota, will be discussed.
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10.
New Insights into the Role of Exercise in Inhibiting mTOR Signaling in Triple-Negative Breast Cancer.
Agostini, D, Natalucci, V, Baldelli, G, De Santi, M, Donati Zeppa, S, Vallorani, L, Annibalini, G, Lucertini, F, Federici, A, Izzo, R, et al
Oxidative medicine and cellular longevity. 2018;:5896786
Abstract
Triple-negative breast cancer (TNBC) does not express estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 and is characterized by its aggressive nature, lack of targets for targeted therapies, and early peak of recurrence. Due to these specific characteristics, chemotherapy does not usually yield substantial improvements and new target therapies and alternative strategies are needed. The beneficial responses of TNBC survivors to regular exercise, including a reduction in the rate of tumor growth, are becoming increasingly apparent. Physiological adaptations to exercise occur in skeletal muscle but have an impact on the entire body through systemic control of energy homeostasis and metabolism, which in turn influence the TNBC tumor microenvironment. Gaining insights into the causal mechanisms of the therapeutic cancer control properties of regular exercise is important to improve the prescription and implementation of exercise and training in TNBC survivors. Here, we provide new evidence of the effects of exercise on TNBC prevention, control, and outcomes, based on the inhibition of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (PKB also known as Akt)/mammalian target of rapamycin (mTOR) (PI3K-Akt-mTOR) signaling. These findings have wide-ranging clinical implications for cancer treatment, including recurrence and case management.