The severity and outcome of coronavirus disease 2019 (COVID-19) largely depends on a patient's age. Adults over 65 years of age represent 80% of hospitalizations and have a 23-fold greater risk of death than those under 65. In the clinic, COVID-19 patients most commonly present with fever, cough and dyspnea, and from there the disease can progress to acute respiratory distress syndrome, lung consolidation, cytokine release syndrome, endotheliitis, coagulopathy, multiple organ failure and death. Comorbidities such as cardiovascular disease, diabetes and obesity increase the chances of fatal disease, but they alone do not explain why age is an independent risk factor. Here, we present the molecular differences between young, middle-aged and older people that may explain why COVID-19 is a mild illness in some but life-threatening in others. We also discuss several biological age clocks that could be used in conjunction with genetic tests to identify both the mechanisms of the disease and individuals most at risk. Finally, based on these mechanisms, we discuss treatments that could increase the survival of older people, not simply by inhibiting the virus, but by restoring patients' ability to clear the infection and effectively regulate immune responses.

Why does COVID-19 disproportionately affect older people?

Abstract Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year‐on‐year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non‐vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its ‘Minimal Information for Studies of Extracellular Vesicles’, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

The reach of tribology has expanded in diverse fields and tribology related research activities have seen immense growth during the last decade. This review takes stock of the recent advances in research pertaining to different aspects of tribology within the last 2 to 3 years. Different aspects of tribology that have been reviewed including lubrication, wear and surface engineering, biotribology, high temperature tribology, and computational tribology. This review attempts to highlight recent research and also presents future outlook pertaining to these aspects. It may however be noted that there are limitations of this review. One of the most important of these is that tribology being a highly multidisciplinary field, the research results are widely spread across various disciplines and there can be omissions because of this. Secondly, the topics dealt with in the field of tribology include only some of the salient topics (such as lubrication, wear, surface engineering, biotribology, high temperature tribology, and computational tribology) but there are many more aspects of tribology that have not been covered in this review. Despite these limitations it is hoped that such a review will bring the most recent salient research in focus and will be beneficial for the growing community of tribology researchers.

/pdf/a-review-of-recent-advances-in-tribology-48dk6nml6e.pdf

A review of recent advances in tribology

Aging is accompanied by profound changes in many physiological functions, leading to a decreased ability to cope with stressors. Many changes are subtle, but can negatively affect nutrient intake, leading to overt malnutrition. Poor oral health may affect food selection and nutrient intake, leading to malnutrition and, consequently, to frailty and sarcopenia. On the other hand, it has been highlighted that sarcopenia is a whole-body process also affecting muscles dedicated to chewing and swallowing. Hence, muscle decline of these muscle groups may also have a negative impact on nutrient intake, increasing the risk for malnutrition. The interplay between oral diseases and malnutrition with frailty and sarcopenia may be explained through biological and environmental factors that are linked to the common burden of inflammation and oxidative stress. The presence of oral problems, alone or in combination with sarcopenia, may thus represent the biological substratum of the disabling cascade experienced by many frail individuals. A multimodal and multidisciplinary approach, including personalized dietary counselling and oral health care, may thus be helpful to better manage the complexity of older people. Furthermore, preventive strategies applied throughout the lifetime could help to preserve both oral and muscle function later in life. Here, we provide an overview on the relevance of poor oral health as a determinant of malnutrition and sarcopenia.

/pdf/poor-oral-health-as-a-determinant-of-malnutrition-and-56orsr8cgi.pdf

Poor Oral Health as a Determinant of Malnutrition and Sarcopenia.

Biological functional entities surround themselves with selective barriers that control the passage of certain classes of macromolecules while rejecting others. A prominent example of such a selective permeability barrier is given by mucus. Mucus is a biopolymer-based hydrogel that lines all wet epithelial surfaces of the human body. It regulates the uptake of nutrients from our gastrointestinal system, adjusts itself with the menstrual cycle to control the passage of sperm, and shields the underlying cells from pathogens such as bacteria and viruses. In the case of drug delivery, the mucus barrier needs to be overcome for successful medical treatment. Despite its importance for both physiology and medical applications, the underlying principles which regulate the permeability of mucus remain enigmatic. Here, we analyze the mobility of microscopic particles in reconstituted mucin hydrogels. We show that electrostatic interactions between diffusing particles and mucin polymers regulate the permeability properties of reconstituted mucin hydrogels. As a consequence, various parameters such as particle surface charge and mucin density, and buffer conditions such as pH and ionic strength, can modulate the microscopic barrier function of the mucin hydrogel. Our findings suggest that the permeability of a biopolymer-based hydrogel such as native mucus can be tuned to a wide range of settings in different compartments of our bodies.

Characterization of Particle Translocation through Mucin Hydrogels

Saliva is crucial to oral processing of food and consequently is also related to the sensory and textural experience. It is often assumed that the secretion and properties of saliva change with age, which can result in dry mouth conditions, taste aberrations. Such changes may result in reduced nutrient intake and malnutrition besides adversely affecting the quality of life. Based on some recent research findings, this article reviews our current understandings on age-dependent changes on quantity (bulk salivary flow rate) as well as quality of saliva (e.g., composition, viscosity, lubrication) in healthy elderly individuals. The review begins with a short introduction to histological changes of salivary glands upon aging. This is followed by covering different aspects of salivary changes with key articles highlighting decreased flow rate, increased ionic concentration, decreased calcium and mucin content in saliva of elderly subjects consequently affecting the oral coating and flavor perception. We also highlight issues in data associated with respect to variance in saliva collection protocols as well as factors influencing such results other than age, such as health conditions and polypharmacy. Clear gaps in literature have been highlighted with respect to lack of quantitative data in viscoelasticity, rheology, and lubrication properties of saliva in healthy elderly population and the potential impact of changes in these material properties on sensory and textural perception of food and consequently food intake. Such insights will not only have clinical implications for maintaining optimal oral health in elderly population but also serve to optimize food for elderly population. PRACTICAL APPLICATIONS: The population has undergone a fundamental change in its age structure globally, with a rapid increase in elderly population. Innovation of tailored foods is still in its early stage to satisfy the needs of growing aging population. One of the biggest challenges in such food product development is lack of adequate understanding and characterization of endogenous factors, that is, age-related changes in saliva, which may influence oral processing of food and subsequently nutrient intake. Aging affects the salivary glands and alters quantity (flow rate) and quality (e.g., ion and protein composition, rheology, tribology) of saliva. Thus, older adults may suffer from dry mouth, taste aberration, and poor oral hygiene, greatly affecting their quality of life. This review provides insights into how age versus other health conditions influence salivary properties. Understanding of age-dependent changes in salivary rheology and tribology will be of paramount importance to optimize food for elderly population.

Aging-related changes in quantity and quality of saliva: Where do we stand in our understanding?

https://backend.orbit.dtu.dk/ws/files/192315652/2019_ACIS.pdf

Human saliva and model saliva at bulk to adsorbed phases - similarities and differences.

Salivary pellicle, a spontaneously formed, intricate architecture in the human oral cavity, is a high‐performance bio‐lubricant that coats and protects biological surfaces with varying elastic modulus against frictional damage. Although salivary lubrication underpins the fundamentals of human feeding and speech, the peculiar molecular mechanism behind such lubrication properties remains elusive. For the first time, this work demonstrates a binary model comprised of salivary proteins, mucin, and lactoferrin (LF), forming an electrostatically driven, multilayered self‐assembly that exhibits a lubrication behavior closely resembling that of human saliva, from macro to nanoscale. The multiscale tribological analysis with applied forces ranging from 1 N to 1 nN, supported by real‐time self‐assembly monitoring on hydrophilic and hydrophobic substrates differentially resolves the distinct roles played by the salivary proteins of this proposed lubricating model. Evidences reveal that hydrated mucin controls the macromolecular viscous lubrication entrapping water molecules in the mucinous network and LF acts as a “molecular glue” between mucin–mucin and mucin–surface, latter aiding boundary lubrication. This study puts forward an unprecedented molecular model that explains the synergistic lubrication by salivary components. These results can aid into the design routes for synthesizing highly efficacious nature‐inspired aqueous lubricants for future biomedical applications and nutritional technologies.

https://onlinelibrary.wiley.com/doi/epdf/10.1002/admi.201901549

A Self‐Assembled Binary Protein Model Explains High‐Performance Salivary Lubrication from Macro to Nanoscale

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Aging-related changes in quantity and quality of saliva: Where do we stand in our understanding?

Human saliva and model saliva at bulk to adsorbed phases - similarities and differences.

A Self‐Assembled Binary Protein Model Explains High‐Performance Salivary Lubrication from Macro to Nanoscale

Data associated with 'A Self‐Assembled Binary Protein Model Explains High‐Performance Salivary Lubrication from Macro to Nanoscale'