scholarly journals Silence of the Lambs: The Immunological and Molecular Mechanisms of COVID-19 in Children in Comparison with Adults

2021 ◽  
Vol 9 (2) ◽  
pp. 330
Author(s):  
Francesca Cusenza ◽  
Giusy Davino ◽  
Tiziana D’Alvano ◽  
Alberto Argentiero ◽  
Valentina Fainardi ◽  
...  
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
Clinical Manifestations ◽  
Pediatric Intensive Care ◽  
The Elderly ◽  
Severe Form ◽  
System Response ◽  
Mild Disease ◽  
Age Related ◽  
Developmental Variations

Children infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can suffer from severe coronavirus disease 2019 (COVID-19). However, compared to adults and the elderly, susceptibility to SARS-CoV-2 infection in children seems to be lower; when infection does develop, most infected children remain asymptomatic or develop a mild disease. Understanding why children seem generally protected from severe COVID-19 and only rarely develop clinical conditions that can cause hospitalization, admission to the pediatric intensive care unit and death can be important. More details on the mechanism of action of SARS-CoV-2 could be defined. Moreover, the role played by children in virus diffusion should be better analyzed, and the development of effective preventive and therapeutic measures against COVID-19 could be favored. The main aim of this paper is to discuss the present knowledge on immunological and molecular mechanisms that could explain differences in COVID-19 clinical manifestations between children and adults. Literature analysis showed that although most children are clearly protected from the development of severe COVID-19, the reasons for this peculiarity are not fully understood. Developmental variations in immune system function together with the potential role of repeated antigen stimulation in the first periods of life on innate immunity are widely studied. As the few children who develop the most severe form of pediatric COVID-19 have certain alterations in the immune system response to SARS-CoV-2 infection, studies about the relationships between SARS-CoV-2 and the immune system of the host are essential to understand the reasons for the age-related differences in the severity of COVID-19.

scholarly journals Causes and Mechanisms of Hematopoietic Stem Cell Aging

2019 ◽  
Vol 20 (6) ◽  
pp. 1272 ◽  
Author(s):  
Jungwoon Lee ◽  
Suk Yoon ◽  
Inpyo Choi ◽  
Haiyoung Jung
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
The Elderly ◽  
Cell Aging ◽  
Extrinsic Factors ◽  
Hematopoietic Stem ◽  
Age Related ◽  
Stem Cell Aging ◽  
Related Stress

Many elderly people suffer from hematological diseases known to be highly age-dependent. Hematopoietic stem cells (HSCs) maintain the immune system by producing all blood cells throughout the lifetime of an organism. Recent reports have suggested that HSCs are susceptible to age-related stress and gradually lose their self-renewal and regeneration capacity with aging. HSC aging is driven by cell-intrinsic and -extrinsic factors that result in the disruption of the immune system. Thus, the study of HSC aging is important to our understanding of age-related immune diseases and can also provide potential strategies to improve quality of life in the elderly. In this review, we delineate our understanding of the phenotypes, causes, and molecular mechanisms involved in HSC aging.

scholarly journals CHRONIC INFLAMMATION IN THE ELDERLY: MECHANISMS AND ASSOCIATION WITH ATHEROSCLEROSIS

2021 ◽  
Vol 20 (2) ◽  
pp. 10-18
Author(s):  
P. A. Zinovev ◽  
I. Zh. Shubina ◽  
V. V. Yamenskov ◽  
M. V. Kiselevskiy
Keyword(s):  
Immune System ◽  
Chronic Inflammation ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Early Stage ◽  
The Elderly ◽  
Cellular Aging ◽  
Inflammatory Factors ◽  
Inflammatory Status ◽  
Age Related

In 2000 Claudio Franceschi first used the term “inflammageing” derived from the English words “inflammation” and “age”. This term refers to the development of chronic inflammation in the elderly, which is characterized by a high level of pro-inflammatory markers of cells and tissues. Cellular aging can be triggered by a variety of factors: critical telomere shortening, permanent DNA damage, epigenetic damage, mitochondrial dysfunction, and an increase in the number of molecular fragments associated with cell damage.A large number of markers have been found to reveal the pro-inflammatory status, such as interleukin (IL) 1, IL-1ra (IL-1 receptor antagonist protein), IL-6, -8, -13, -18, C-reactive protein, interferons α, β, transforming growth factor β, tumor necrosis factor α and its soluble receptors and SAA-1 (serum amyloid А1). The molecular mechanisms associated with aging and age-related diseases are not clear yet, while sluggish chronic inflammation is one of the leading mechanisms for the atherosclerosis development. Remodeling of the immune system with the increasing production of pro-inflammatory cytokines and NLRP3 inflammasomes also play a key role in the maintenance of chronic inflammation due to its ability to pick up a variety of age-related dangerous signals that trigger the immune response and subsequent inflammation and may act as a factor of the atherosclerosis development.Thus, pro-inflammatory factors of the immune system play an important role in pathogenesis of atherosclerosis,especially at an early stage, involving various mechanisms of action that boost atherosclerotic changes.

scholarly journals Neuroinflammation and Its Impact on the Pathogenesis of COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Mohammed M. Almutairi ◽  
Farzane Sivandzade ◽  
Thamer H. Albekairi ◽  
Faleh Alqahtani ◽  
Luca Cucullo
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Immune Cell ◽  
Clinical Manifestations ◽  
Cell Infiltration ◽  
Cellular Mechanisms ◽  
Cytokine Levels

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical manifestations of COVID-19 include dry cough, difficult breathing, fever, fatigue, and may lead to pneumonia and respiratory failure. There are significant gaps in the current understanding of whether SARS-CoV-2 attacks the CNS directly or through activation of the peripheral immune system and immune cell infiltration. Although the modality of neurological impairments associated with COVID-19 has not been thoroughly investigated, the latest studies have observed that SARS-CoV-2 induces neuroinflammation and may have severe long-term consequences. Here we review the literature on possible cellular and molecular mechanisms of SARS-CoV-2 induced-neuroinflammation. Activation of the innate immune system is associated with increased cytokine levels, chemokines, and free radicals in the SARS-CoV-2-induced pathogenic response at the blood-brain barrier (BBB). BBB disruption allows immune/inflammatory cell infiltration into the CNS activating immune resident cells (such as microglia and astrocytes). This review highlights the molecular and cellular mechanisms involved in COVID-19-induced neuroinflammation, which may lead to neuronal death. A better understanding of these mechanisms will help gain substantial knowledge about the potential role of SARS-CoV-2 in neurological changes and plan possible therapeutic intervention strategies.

scholarly journals Updates on Old and Weary Haematopoiesis

2018 ◽  
Vol 19 (9) ◽  
pp. 2567 ◽  
Author(s):  
Joanna Konieczny ◽  
Lorena Arranz
Keyword(s):  
Molecular Mechanisms ◽  
The Elderly ◽  
Progressive Decline ◽  
Cell Functions ◽  
Age Related ◽  
High Incidence ◽  
Hsc Niche ◽  
Blood Formation ◽  
External Stimuli ◽  
Future Work

Blood formation, or haematopoiesis, originates from haematopoietic stem cells (HSCs), whose functions and maintenance are regulated in both cell- and cell non-autonomous ways. The surroundings of HSCs in the bone marrow create a specific niche or microenvironment where HSCs nest that allows them to retain their unique characteristics and respond rapidly to external stimuli. Ageing is accompanied by reduced regenerative capacity of the organism affecting all systems, due to the progressive decline of stem cell functions. This includes blood and HSCs, which contributes to age-related haematological disorders, anaemia, and immunosenescence, among others. Furthermore, chronological ageing is characterised by myeloid and platelet HSC skewing, inflammageing, and expanded clonal haematopoiesis, which may be the result of the accumulation of preleukaemic lesions in HSCs. Intriguingly, haematological malignancies such as acute myeloid leukaemia have a high incidence among elderly patients, yet not all individuals with clonal haematopoiesis develop leukaemias. Here, we discuss recent work on these aspects, their potential underlying molecular mechanisms, and the first cues linking age-related changes in the HSC niche to poor HSC maintenance. Future work is needed for a better understanding of haematopoiesis during ageing. This field may open new avenues for HSC rejuvenation and therapeutic strategies in the elderly.

scholarly journals Targeting Age-Related Pathways in Heart Failure

2020 ◽  
Vol 126 (4) ◽  
pp. 533-551 ◽  
Author(s):  
Haobo Li ◽  
Margaret H. Hastings ◽  
James Rhee ◽  
Lena E. Trager ◽  
Jason D. Roh ◽  
...  
Keyword(s):  
Heart Failure ◽  
Elderly Population ◽  
Molecular Mechanisms ◽  
The Elderly ◽  
Structure And Function ◽  
Experimental Platform ◽  
Age Related ◽  
Cardiac Structure And Function ◽  
And Function ◽  
Increased Susceptibility

During aging, deterioration in cardiac structure and function leads to increased susceptibility to heart failure. The need for interventions to combat this age-related cardiac decline is becoming increasingly urgent as the elderly population continues to grow. Our understanding of cardiac aging, and aging in general, is limited. However, recent studies of age-related decline and its prevention through interventions like exercise have revealed novel pathological and cardioprotective pathways. In this review, we summarize recent findings concerning the molecular mechanisms of age-related heart failure and highlight exercise as a valuable experimental platform for the discovery of much-needed novel therapeutic targets in this chronic disease.

scholarly journals Central Role of Oxidative Stress in Age-Related Macular Degeneration: Evidence from a Review of the Molecular Mechanisms and Animal Models

2020 ◽  
Vol 2020 ◽  
pp. 1-19 ◽  
Author(s):  
Samuel Abokyi ◽  
Chi-Ho To ◽  
Tim T. Lam ◽  
Dennis Y. Tse
Keyword(s):  
Oxidative Stress ◽  
Animal Models ◽  
Macular Degeneration ◽  
Molecular Mechanisms ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Related Factor ◽  
Vascular Endothelial ◽  
Age Related ◽  
Endothelial Growth Factor

Age-related macular degeneration (AMD) is a common cause of visual impairment in the elderly. There are very limited therapeutic options for AMD with the predominant therapies targeting vascular endothelial growth factor (VEGF) in the retina of patients afflicted with wet AMD. Hence, it is important to remind readers, especially those interested in AMD, about current studies that may help to develop novel therapies for other stages of AMD. This study, therefore, provides a comprehensive review of studies on human specimens as well as rodent models of the disease, to identify and analyze the molecular mechanisms behind AMD development and progression. The evaluation of this information highlights the central role that oxidative damage in the retina plays in contributing to major pathways, including inflammation and angiogenesis, found in the AMD phenotype. Following on the debate of oxidative stress as the earliest injury in the AMD pathogenesis, we demonstrated how the targeting of oxidative stress-associated pathways, such as autophagy and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, might be the futuristic direction to explore in the search of an effective treatment for AMD, as the dysregulation of these mechanisms is crucial to oxidative injury in the retina. In addition, animal models of AMD have been discussed in great detail, with their strengths and pitfalls included, to assist inform in the selection of suitable models for investigating any of the molecular mechanisms.

Primary Aldosteronism in the Elderly

2020 ◽  
Vol 105 (7) ◽  
pp. e2320-e2326
Author(s):  
Paolo Mulatero ◽  
Jacopo Burrello ◽  
Tracy Ann Williams ◽  
Silvia Monticone
Keyword(s):  
Primary Aldosteronism ◽  
Molecular Mechanisms ◽  
Sodium Intake ◽  
Evidence Synthesis ◽  
Expression Patterns ◽  
The Elderly ◽  
Zona Glomerulosa ◽  
Endocrine Society ◽  
Age Related ◽  
Serum Aldosterone

Abstract Context The clinical spectrum and knowledge of the molecular mechanisms underlying primary aldosteronism (PA), the most frequent form of endocrine hypertension, has evolved over recent years. In accordance with the Endocrine Society guidelines and in light of the growing evidence showing adverse cardiovascular outcomes, it is expected that a progressively wider population of patients affected by hypertension will be screened for PA, including the elderly. Evidence Acquisition A systematic search of PubMed was undertaken for studies related to the renin-angiotensin-aldosterone system (RAAS), PA, and adrenal histopathology in the elderly population. Evidence Synthesis Several studies showed an age-dependent decrease in the activity of RAAS, together with a progressive decrease of the aldosterone response to sodium intake, particularly after the sixth decade of life. The positive correlation between age and serum aldosterone during liberal sodium intake over serum aldosterone during sodium restriction is paralleled by histological changes in adrenal aldosterone synthase (CYP11B2) expression patterns. Immunohistochemical studies showed a progressive loss of the continuous expression of CYP11B2 in the adrenal zona glomerulosa with aging and a concomitant increase of aldosterone-producing cell clusters, which might be responsible for relatively autonomous aldosterone production. Additionally, following PA confirmation and subtype diagnosis, older age is correlated with a lower benefit after adrenalectomy for unilateral PA. Conclusions Accumulating evidence suggests that RAAS physiology and regulation show age-related changes. Further studies may investigate to what extent these variations might affect the diagnostic workup of patients affected by PA.

scholarly journals Uncovering the Neuroprotective Mechanisms of Curcumin on Transthyretin Amyloidosis

2019 ◽  
Vol 20 (6) ◽  
pp. 1287 ◽  
Author(s):  
Nelson Ferreira ◽  
Maria Saraiva ◽  
Maria Almeida
Keyword(s):  
Immune System ◽  
Amino Acid ◽  
Molecular Mechanisms ◽  
Clinical Manifestations ◽  
Current Work ◽  
Amino Acid Substitutions ◽  
Therapeutic Approaches ◽  
Transthyretin Amyloidosis ◽  
Chemical Chaperones ◽  
Attr Amyloidosis

Transthyretin (TTR) amyloidoses (ATTR amyloidosis) are diseases associated with transthyretin (TTR) misfolding, aggregation and extracellular deposition in tissues as amyloid. Clinical manifestations of the disease are variable and include mainly polyneuropathy and/or cardiomyopathy. The reasons why TTR forms aggregates and amyloid are related with amino acid substitutions in the protein due to mutations, or with environmental alterations associated with aging, that make the protein more unstable and prone to aggregation. According to this model, several therapeutic approaches have been proposed for the diseases that range from stabilization of TTR, using chemical chaperones, to clearance of the aggregated protein deposited in tissues in the form of oligomers or small aggregates, by the action of disruptors or by activation of the immune system. Interestingly, different studies revealed that curcumin presents anti-amyloid properties, targeting multiple steps in the ATTR amyloidogenic cascade. The effects of curcumin on ATTR amyloidosis will be reviewed and discussed in the current work in order to contribute to knowledge of the molecular mechanisms involved in TTR amyloidosis and propose more efficient drugs for therapy.

scholarly journals Role of Senescence and Aging in SARS-CoV-2 Infection and COVID-19 Disease

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3367
Author(s):  
Seodhna M. Lynch ◽  
Guangran Guo ◽  
David S. Gibson ◽  
Anthony J. Bjourson ◽  
Taranjit Singh Rai
Keyword(s):  
Immune System ◽  
Severe Disease ◽  
Severe Infection ◽  
The Elderly ◽  
System Response ◽  
Aging Research ◽  
Global Pandemic ◽  
Immune System Response ◽  
Response Current

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic associated with substantial morbidity and mortality worldwide, with particular risk for severe disease and mortality in the elderly population. SARS-CoV-2 infection is driven by a pathological hyperinflammatory response which results in a dysregulated immune response. Current advancements in aging research indicates that aging pathways have fundamental roles in dictating healthspan in addition to lifespan. Our review discusses the aging immune system and highlights that senescence and aging together, play a central role in COVID-19 pathogenesis. In our review, we primarily focus on the immune system response to SARS-CoV-2 infection, the interconnection between severe COVID-19, immunosenescence, aging, vaccination, and the emerging problem of Long-COVID. We hope to highlight the importance of identifying specific senescent endotypes (or “sendotypes”), which can used as determinants of COVID-19 severity and mortality. Indeed, identified sendotypes could be therapeutically exploited for therapeutic intervention. We highlight that senolytics, which eliminate senescent cells, can target aging-associated pathways and therefore are proving attractive as potential therapeutic options to alleviate symptoms, prevent severe infection, and reduce mortality burden in COVID-19 and thus ultimately enhance healthspan.

scholarly journals Novel Programmed Cell Death as Therapeutic Targets in Age-Related Macular Degeneration?

2020 ◽  
Vol 21 (19) ◽  
pp. 7279 ◽  
Author(s):  
Ming Yang ◽  
Kwok-Fai So ◽  
Wai Ching Lam ◽  
Amy Cheuk Yin Lo
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Macular Degeneration ◽  
Molecular Mechanisms ◽  
Cell Damage ◽  
Retinal Pigment ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Severe Visual Loss ◽  
Age Related

Age-related macular degeneration (AMD) is a leading cause of severe visual loss among the elderly. AMD patients are tormented by progressive central blurring/loss of vision and have limited therapeutic options to date. Drusen accumulation causing retinal pigment epithelial (RPE) cell damage is the hallmark of AMD pathogenesis, in which oxidative stress and inflammation are the well-known molecular mechanisms. However, the underlying mechanisms of how RPE responds when exposed to drusen are still poorly understood. Programmed cell death (PCD) plays an important role in cellular responses to stress and the regulation of homeostasis and diseases. Apart from the classical apoptosis, recent studies also discovered novel PCD pathways such as pyroptosis, necroptosis, and ferroptosis, which may contribute to RPE cell death in AMD. This evidence may yield new treatment targets for AMD. In this review, we summarized and analyzed recent advances on the association between novel PCD and AMD, proposing PCD’s role as a therapeutic new target for future AMD treatment.

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