1,721,017 research outputs found
Experimental models for ageing research
Full text link: Ageing is a biological process caused by the malfunctioning of multiple cellular mechanisms, ascribable to nine hallmarks: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. These ageing pillars have three common traits: (i) they appear during normal ageing; (ii) their experimental intensification accelerates ageing; and (iii) their experimental reduction delays ageing. The evidence that the elderly are more prone to develop pathologies such as cancer, diabetes and degenerative diseases, together with data showing that the elderly population is steadily increasing, has stimulated an important effort to find specific countermeasures to physiological ageing. Unfortunately, the investigation of ageing processes and the search for countermeasures in humans is very difficult. Therefore, researchers must rely on a wide range of experimental models that span from unicellular to more complex organisms. Unfortunately, experimental models are not devoid of pitfalls, flaws or obstacles that can have an impact in ageing research. In the present review we describe the most exploited experimental models in the field, such as in vitro, animal and human models, highlighting the characteristics that justify their application in the laboratory routine, and translation to human research
Analysis of the fiber profile of skeletal muscle
No full textSkeletal muscles display a unique plasticity, which responds to the rapid changes of the organism activity, nutritional habits, health conditions, genetic background, and other factors (Schiaffino and Reggiani, 2011; Sirago et al., 2022). The muscle is composed by multiple fibers that have different contractile characteristics. Skeletal muscle fibers differ one from another in the contractile apparatus composition, calcium handling properties, number of mitochondria, and morphological features (Schiaffino and Reggiani, 2011; Giacomello et al., 2020). We refer to the term “fiber profile” to all the features, such as MHC expression, morphology and metabolic activity, that characterize a single muscle fiber. In general, the isoforms of Myosin Heavy Chain (MyHC) expressed in a muscle fiber, are considered the gold standard in the correlation of the morphological, contractile, and metabolic properties. Interestingly, recent data show that both in rodent and human muscles, morphological and metabolic characteristics of fibers expressing the same MyHCs can significantly diverge.
In the present project we investigated the different fiber profile of skeletal muscle fibers expressing MyHCI and IIa in soleus and exstensor digitorum longus muscles.
This data was selected as part of the AI4Life Open Calls 2023 for image analysis consultation and deep-learning applications
Editorial: Aging and frailty: from causes to prevention
Full text linkIntroduction:
Recent improvement in sanitary, nutritional, and socioeconomic conditions has led to an increase in life expectancy. As a result, by 2050, people aged more than 60 years are expected to double, and people aged more than 80 years are expected to triple (https://www.who.int/news- room/fact-sheets/detail/ageing-and-health). Unfortunately, increased lifespan, is not always paralleled by an adequate healthspan, because of interference of social, behavioral, physiological, cellular, molecular, and less known factors (Balcombe and Sinclair, 2001). This complexity makes difficult the definition of aging, and challenging management of this period of life.
Aging is accompanied by decline of the individual resulting in a complex condition called frailty, characterized by loss of physical and psychological abilities, and by an amplified vulnerability to stress factors (Morley et al., 2013; Hoogendijk et al., 2019). To limit the impact of frailty on wellbeing and on society, to improve both preventive actions and management, a deep understanding of this condition is needed.
Considering frailty as a geriatric syndrome, we need to understand its etiology, define diagnostic parameters, and apply therapeutic and prevention approaches. This Research Topic was aimed at collecting new knowledge on different aspects of frailty. It comprises 13 research articles that provide new information in different aspects of aging and frailty, such as comprehension of molecular determinants and socioeconomic influence, frailty definition and biomarkers, impact on health outcomes, and prevention strategies.
Biological basis of frailty:
Frailty is the result of a multisystem derangement that involves metabolic unbalance, systemic inflammation, musculoskeletal malfunctioning and altered responses to stress (Picca et al., 2022). Among the multiple biological variables involved in aging and muscle weakness (Picca et al., 2022; Li et al., 2024; Sato et al., 2024), the genetic background captures much interest (Baghdadi et al., 2022; Sirago et al., 2022). Interestingly, Krasniqi et al. report on the impact of genetic variants of vitamin D receptor on muscular fitness in middle aged and older adults. This evidence confirmsthe importance of biological mechanisms and calls for further analysis of genetic predisposition to develop individual strategies.
Socioeconomic influence on frailty:
Recent data evidence that biological variables are not the only determinants of frailty, on the contrary, they highlight the role of variables related to the socioeconomic status of individuals, stimulating the interest to analyze the correlation among frailty and socioeconomic conditions. Accordingly, in the present topic several articles investigate this important theme. The Chinese Longitudinal Healthy Longevity Survey (CLHLS 2008–2018) reveals that higher levels of frailty and lower levels of social participation exhibit significant bidirectional relationships with age, education level, marital status, and drinking habits (Bi et al.). Analogously, Rahman et al., suggest that health outcomes following traumatic brain injury in Bangladesh depend on socioeconomic settings, since lower status individuals have limited access to treatments. Moreover, as highlighted by Czyżewski et al., geriatric patients, lacking their independence, need special care, that can be provided depending on their location. Their data propose that the number of accesses to emergency from rural areas-based patients prevail to those from the urban areas, maybe due to limited access to a primary care physician.
Frailty definition and biomarkers:
Frailty is a dynamic condition that can appear with physiological, psychological signs or both, making difficult the evaluation of risk factors and formulation of a diagnosis (Morley et al., 2013). The multifactorial nature, and the diverse clinical manifestations limit the establishment of a unequivocal frailty score (Rockwood et al., 2007). According to above reported observations, the evaluation of frailty risk should include both biomarkers and socioeconomic parameters. From the physiological point of view, frailty is characterized by a low- grade chronic inflammation. Therefore, inflammatory markers seem good candidates to help to define and diagnose frailty. In this context, Zhang et al., based on data from the United States National Health and Nutrition Examination Survey (NHANES, 2007–2018), suggest that Systemic Immune-Inflammation Index (SII) and Systemic Inflammatory Response Index (SIRI) could be used as markers of frailty. From the analysis of 16,705 middle-aged and older participants to NHANES 1999–2018, Tang et al. found six complete blood count- derived inflammatory markers (neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, SII, SIRI, and pan-immune inflammation value), which are associated with higher risk of frailty and mortality. Since frailty is also accompanied by a sensible reduction of skeletal muscle strength and endurance, Fujikawa et al. suggest bimanual coordinated movements analyses to assess levels of frailty. From a study on 358 community-dwelling older adults, they found that frail adults exhibit less movement during bimanual coordination tasks compared with non-frail adults. Interestingly, Lin et al., who aimed at assessing the risk of frailty in older adults affected by atrial fibrillation, suggest a comprehensive predictive model based on multiple risk factors, such as age, gender, history of coronary heart disease, number of chronic conditions, sleep quality, and mental health condition. In agreementwith the multifactorial nature of frailty, a comprehensive method could be helpful in obtaining a broader picture of frail individuals and fundamental to frailty management.
Therapeutic, prevention and care approaches:
In clinical situations, frail individuals could require different care and may have different outcomes to health challenges, therefore assessment of frailty may provide important decision-making information. In this context, the article from Adamuz et al. reports that COVID-19 patients older than 75 years presented more care complexity individual factors (CCIFs), especially those related to comorbidity, cognitive and social impairment, than younger subjects. On the other side, Ma et al. suggest that frailty is a good parameter to predict postoperative disability after cardiac surgery. Lastly, from their investigation on impact of age and frailty on key clinical outcomes from liver transplants, Valenti et al., found that frailty, rather than age, is a predictor of mortality. Considered the social impact of frailty in several aspects of daily life, there is a growing interest on both healthcare system and community interventions that could reduce the effects of frailty. A study from Ni et al., emphasize the consequence of different activities on frailty of older adults in China. Actually, from the China Health and Retirement Longitudinal Study (CHARLS 2020), it emerges that physical, social, economic, information and sleep activity have positive effects on frailty. Interestingly, a case study reporting a community-based early frailty intervention program delivered by trained laypersons in Singapore, indicates that in an initial phase older adults can be supported by non-healthcare professionals that control physical activity and nutrition of participants (Jayaprakash et al.). Nevertheless, although programs managed by trained laypersons could be an initial step towards awareness of frailty and an initial action towards its combat, these programs need supports and resources, and involvement of healthcare systems (Cesari et al., 2016).
Frailty is a complex multifactorial condition that can accompany aging with multiple pathophysiological manifestations, making each frail individual rather unique. Articles included in this topic provide new knowledge on frailty, confirm the role of biological variables and highlight the weight of socioeconomic factors, that should be considered in the evaluation of risks, diagnosis and therapeutical approaches. Hopefully, new knowledge will increase awareness of frailty, and involvement of society and healthcare systems to promote prevention and care strategies (Cesari et al., 2016)
Exercise Mimetics in Aging: Suggestions from a Systematic Review
Full text linkBackground/Objectives: Growth in the aging world population is accompanied by an increase in comorbidities, profoundly impacting the quality of life of older people. This development has motivated a large effort to investigate the mechanisms underlying aging and the search for countermeasures. The most investigated strategies envisage the control of diet and physical exercise, which exploit both common and distinct mechanisms to promote health. Since the application of nutritional and exercise protocols to aged persons introduces several issues due to their disabled state, some strategies have been developed. The nutritional approach exploits a wide range of compounds, including calorie restriction mimetics, supplements, antioxidants, and others. In the context of exercise, in recent years, molecules able to provide similar effects to exercise, the so-called exercise mimetics, have been developed. Methods: To have a better perspective on exercise mimetics and their connection with nutrition, we performed a systematic search of the PubMed and Scopus databases using the term “exercise mimetics”. Results: In total, 97 research articles were selected and discussed. The present review provides evidence of the presence of multiple exercise-mimetic compounds and physical strategies that can target metabolic pathways, oxidative stress defense mechanisms, or myokine modulation. Conclusions: Interestingly, this review highlights that an important number of exercise mimetics are represented by products of natural origin and supplements assimilable with diet. This evidence provides a further link between exercise and nutrition and confers a central role on nutrition in the context of exercise mimetics
Localization of ank1.5 in the sarcoplasmic reticulum precedes that of SERCA and RyR: relationship with the organization of obscurin in developing sarcomeres
No full textAnk1.5 is a muscle-specific isoform of ankyrin1 localized on the sarcoplasmic reticulum (SR) membrane that has been shown to interact with obscurin, a sarcomeric protein. We report here studies on the localization of obscurin and ank1.5 in embryonic and postnatal rodent skeletal muscles. Using two antibodies against epitopes in the N- and C-terminus of obscurin, two distinct patterns of localization were observed. Before birth, the antibodies against the N- and the C-terminus of obscurin stained the Z-disk and M-band, respectively. At the same time, ank1.5 was detected at the Z-disk, rising the possibility that obscurin molecules at M-band may not be able to interact with ank1.5. Localization of ank1.5 at Z-disks in E14 muscle fibers revealed that ank1.5 is among the earliest SR proteins to assemble, since its organization preceded that of other SR proteins, like SERCA and RyR. After birth, the antibody against the N-terminus of obscurin stained the M-band while that against the C-terminus stained both M-bands and the Z-disks. Starting from postnatal day 1, ank1.5 was found at the level of both M-bands and Z-disks. Altogether, from these results we infer that exposure of some obscurin epitopes changes during skeletal muscle development, resulting in distinct, antibody-specific, localization pattern. Why this occurs is not clear, yet these data indicate that the organization of obscurin at different locations in the sarcomere changes during muscle development and that this might affect the interaction with ank1.5
A short-term treatment with resveratrol improves the inflammatory conditions of Middle-aged mice skeletal muscles
No full textSarcopenia starts around the age of 40, causes the loss of 8% of muscle mass every 10 years, and is accompanied by functional deficit, chronic low-grade inflammation, and can result in several negative health outcomes. Considering the early and gradual onset of sarcopenia, the time window of the potential interventions could be crucial for the exertion of a beneficial effect. We recently showed that the long-term supplementation with Resveratrol contrasts sarcopenia in naturally ageing C57BL/6 mice. Aiming to understand the effects of a short term treatment, we administered intraperitoneally middle aged male mice with 20 mg/kg body weight Resveratrol daily for 5 weeks. Although we could not observe major differences in the histological properties of SKMs, we detected a significant decrease of Cox-2 in RES-treated muscles, confirming the antiinflammatory action of Resveratrol, and suggesting that its anti-inflammatory action precedes modifications to SKM fibres
Resveratrol, a Multitasking Molecule That Improves Skeletal Muscle Health
Full text linkResveratrol is a natural polyphenol utilized in Chinese traditional medicine and thought to be one of the determinants of the "French Paradox". More recently, some groups evidenced its properties as a calorie-restriction mimetic, suggesting that its action passes through the modulation of skeletal muscle metabolism. Accordingly, the number of studies reporting the beneficial effects of resveratrol on skeletal muscle form and function, in both experimental models and humans, is steadily increasing. Although studies on animal models confer to resveratrol a good potential to ameliorate skeletal muscle structure, function and performance, clinical trials still do not provide clear-cut information. Here, we first summarize the effects of resveratrol on the distinct components of the skeletal muscle, such as myofibers, the neuromuscular junction, tendons, connective sheaths and the capillary bed. Second, we review clinical trials focused on the analysis of skeletal muscle parameters. We suggest that the heterogeneity in the response to resveratrol in humans could depend on sample characteristics, treatment modalities and parameters analyzed; as well, this heterogeneity could possibly reside in the complexity of skeletal muscle physiology. A systematic programming of treatment protocols and analyses could be helpful to obtain consistent results in clinical trials involving resveratrol administration
Morphological Modifications of the Early Secretory Pathway in Differentiating Skeletal Muscle Cells
No full textSkeletal muscle (SKM) cells present a regular and striking arrangement of organelles and membrane systems that is essential for their function. It has been largely investigated on the structural events occurring during the organization of transverse (T) tubules, sarcoplasmic reticulum (SR), and Calcium Release Units (CRUs), and it has been proposed that during SKM differentiation, membrane systems follow a highly coordinated plan.
In addition, SKM cell differentiation and remodeling requires synthesis and transport of an enormous amount of proteins addressed to build up the contractile apparatus, the SR and the sarcolemma. This process most probably requires an important involvement of endoplasmic reticulum (ER), ER exit sites (ERES), Golgi Complex (GC), or early secretory pathway components, and vesicular traffic in general.
In terminally differentiated skeletal muscle cells early secretory pathway components are regularly arranged; the GC is organized in a unique fashion, fiber-type dependent and, formed by very small GC elements, which are localized around the nucleus and in all the fiber. GC elements in mature muscle fibers are very small compared to other cells, but still formed by cisternae. It has been shown that GC undergoes a dramatic reorganization during SKM cell differentiation resulting in the formation of small elements, and interestingly, in mature myotubes GC is found associated to ERES. Whether GC reorganization consists in fragmentation or ex-novo biogenesis is not known, and whether its co-localization with ERES is the result of structural hindrance by the myofibrils and membrane systems, or depends on interaction mechanisms has not been explained.
The present work is aimed at a better understanding how GC and ERES achieve their mature structure, what is their role during SKM differentiation, and whether morphological modifications are followed by alterations of membrane traffic efficiency. Therefore we investigated the processes underlying the morphological transformation of the secretory pathway structures as CG and ER exit sites (ERES) during SKM differentiation. The project envisaged the analysis of the localization of selected markers of secretory pathway components in C2C12 differentiating myoblasts and regenerating fibers by applying imaging techniques in order to follow the differentiation of the early secretory pathway compartments.
We report preliminary data on the morphological modifications occurring to GC and ERES in differentiated C2C12 cells
Golgi Complex form and Function: A Potential Hub Role Also in Skeletal Muscle Pathologies?
Full text linkA growing number of disorders has been associated with mutations in the components of the vesicular transport machinery. The early secretory pathway consists of Endoplasmic Reticulum, numerous vesicles, and the Golgi Complex (GC), which work together to modify and package proteins to deliver them to their destination. The GC is a hub organelle, crucial for organization of the other secretory pathway components. As a consequence, GC’s form and function are key players in the pathogenesis of several disorders. Skeletal muscle (SKM) damage can be caused by defective protein modifications and traffic, as observed in some Limb girdle muscular dystrophies. Interestingly, in turn, muscle damage in Duchenne dystrophic SKM cells also includes the alteration of GC morphology. Based on the correlation between GC’s form and function described in non-muscle diseases, we suggest a key role for this hub organelle also in the onset and progression of some SKM disorders. An altered GC could affect the secretory pathway via primary (e.g., mutation of a glycosylation enzyme), or secondary mechanisms (e.g., GC mis-localization in Duchenne muscles), which converge in SKM cell failure. This evidence induces considering the secretory pathway as a potential therapeutic target in the treatment of muscular dystrophies
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