scholarly journals Early-life inflammation, immune response and ageing

2017 ◽  
Vol 284 (1850) ◽  
pp. 20170125 ◽  
Author(s):  
Imroze Khan ◽  
Deepa Agashe ◽  
Jens Rolff
Keyword(s):  
Immune Response ◽  
Tissue Damage ◽  
Early Life ◽  
Human Kidney ◽  
Malpighian Tubules ◽  
Older Individuals ◽  
Direct Role ◽  
Adult Lifespan ◽  
Age Related

Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response.

scholarly journals Early inflammation, immunopathology and aging

2016 ◽  
Author(s):  
Imroze Khan ◽  
Deepa Agashe ◽  
Jens Rolff
Keyword(s):  
Immune Response ◽  
Tissue Damage ◽  
Early Life ◽  
Malpighian Tubules ◽  
Older Individuals ◽  
Direct Role ◽  
Immune Effector ◽  
Adult Lifespan ◽  
Age Related

ABSTRACTAge-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase (PO), an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage, in turn accelerating aging. In support of this hypothesis, we found that RNAi knockdown of PO transcripts in young adults reduced inflammation-induced autoreactive tissue damage to Malpighian tubules, and increased adult lifespan. Our work thus provides empirical evidence for a causative link between immunopathological costs of early life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, they displayed exacerbated immunopathological costs and higher post-infection mortality. RNAi-mediated knockdown of PO response reduced immunopathology in older beetles and increased their lifespan after infection. This is the first demonstration of a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of immunopathology under diverse contexts of aging and immune response.

scholarly journals VACCINATION TO PROMOTE HEALTH THROUGHOUT LIFE AS A HEALTHY AGING STRATEGY

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S211-S211
Author(s):  
Leonard Friedland
Keyword(s):  
Immune Response ◽  
Healthy Aging ◽  
New Technologies ◽  
Older Age ◽  
Target Antigen ◽  
Older Individuals ◽  
Demographic Shift ◽  
Age Related ◽  
Important Progress

Abstract This symposium addresses the role of vaccination to promote healthy aging, the process of developing and maintaining the functional ability that enables wellbeing in older age. Life-span immunization of adults across all age categories can help to reduce morbidity and mortality. Healthy aging is critical for our global society to counter the surge in healthcare costs that is coming as a result of the demographic shift to older age. Immune system function and response to vaccination declines with advancing age. Generating effective immune responses against new infectious disease targets can be difficult in older individuals. Important progress has been made in understanding the mechanisms underlying immunosenescence, the age-related decline of the immune response to infections and vaccinations. Innovative research and the development of new technologies, such as adjuvants, substances that can enhance and shape the immune response to the target antigen(s), has facilitated the development of vaccines specially tailored for adults. This evidence-based approach to the development of innovative vaccines addressing immunosenescence is an important clinically relevant healthy aging strategy to promote health throughout life.

scholarly journals The beginnings of Alzheimer’s disease: A review on inflammatory, mitochondrial, genetic and epigenetic pathways

Genetika ◽  
2016 ◽  
Vol 48 (2) ◽  
pp. 515-524
Author(s):  
Simone Perna ◽  
Chiara Bologna ◽  
Pietro Cavagna ◽  
Luisa Bernardinelli ◽  
Davide Guido ◽  
...  
Keyword(s):  
Risk Factors ◽  
Amyloid Beta Protein ◽  
Case Control Studies ◽  
Direct Role ◽  
Mtdna Haplogroups ◽  
Multifactorial Diseases ◽  
Age Related ◽  
Apolipoprotein E Gene ◽  
Genes Encoding

Alzheimer?s Disease (AD) is the most common cause of sporadic dementia, as it affects 60% of cognitive impaired patients; it commonly affects middle and late life, and it is considered an age-related disease. Early-onset familial AD is associated with mutations of the genes encoding amyloid precursor protein (APP), presenilin 1 (PS-1), or PS-2, resulting in the overproduction of amyloid beta-protein. Epidemiological and case-control studies have led to the identification of several risk factors for sporadic AD. The most concrete genetic risk factor for AD is the epsilon4 allele of apolipoprotein E gene (APOE). In addition, several genes such as CTNNA3, GAB2, PVRL2, TOMM40, and APOC1 are known to be the risk factors that contribute to AD pathogenesis. A direct role of interaction between genetic and environmental determinants has been proposed in an epigenetic dynamic for environmental factors operating during the preconceptual, fetal and infant phases of life. Also the the association between mtDNA inherited variants and multifactorial diseases and AD has been investigated by a number of studies that, however, didn?t reach a general consensus on the correlation between mtDNA haplogroups and AD.

scholarly journals Decline in rates of clearance of IgG-sensitized erythrocytes with increasing age

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1726-1730
Author(s):  
KA Melez ◽  
LF Fries ◽  
BS Bender ◽  
T Quinn ◽  
MM Frank
Keyword(s):  
Aging Process ◽  
Elderly Population ◽  
The Elderly ◽  
Older Individuals ◽  
Immune Functions ◽  
Macrophage Function ◽  
Normal Volunteers ◽  
Age Related ◽  
Male Subjects

Decreased immune functions have been suggested as a cause for the increased incidence of autoimmunity, malignancy, and infection in the elderly population. To assess the possible role of changes in macrophage function in the aging process we studied the Fc receptor- mediated clearance of IgG-coated erythrocytes in 56 healthy normal volunteers by following the removal of radiolabeled autologous erythrocytes. An age-related decrease in Fc-mediated clearance rates in both female and male subjects was found, which suggests a physiological decline of this macrophage function in older individuals.

scholarly journals The role of balanced supplementation in diet of age-related macular degeneration patients

2021 ◽  
Vol 8 (1) ◽  
pp. 19-25
Author(s):  
Iwona Kusz vel Sobczuk ◽  
Anna Święch
Keyword(s):  
Vitamin D ◽  
Immune Response ◽  
Macular Degeneration ◽  
Vitamin B6 ◽  
Age Related Macular Degeneration ◽  
Response Modulation ◽  
Omega 3 ◽  
Age Related ◽  
Immune Response Modulation

Aim: The aim of the article was to discuss the role of balanced supplementation in diet of age-related macular degeneration patients. Methods: This review was carried out using comprehensive and systematic literature reports on the role of supplementation of vitamin D, vitamin C, vitamin E, vitamin B6, vitamin B12, zinc, lutein, zeaxanthin, omega-3 acid and folic acid in the prevention of AMD. Results: Vitamins, minerals and carotenoids are essential for the proper retinal function over an inflammation and immune response modulation. Conclusions: Vitamins, minerals and carotenoids discussed in the article have anti-inflammatory and antioxidative properties in the management of AMD progression. Accordingly, it is relevant to assure the appropriate level of these nutrients in a diet of AMD patients.

scholarly journals Src-like Adaptor Protein Promotes the CD103+ dendritic Cell Homeostasis in the Lung

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1339-1339
Author(s):  
Namit Sharma ◽  
Pan Zhongda ◽  
Tracy Lauren Smith ◽  
Savar Kaul ◽  
Emilie Ernoult ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Immune Cell ◽  
Conflicts Of Interest ◽  
Adaptor Protein ◽  
Cell Receptor ◽  
Apoptotic Cells ◽  
Direct Role

Abstract Dendritic cells (DCs) along with mast cells function as sentinels for the innate immune system and perform as antigen presenting cells (APCs) to mount an adaptive immune response against invading pathogen. FLT3 receptor tyrosine kinase signaling has been shown to regulate the homeostatic mechanisms of subsets of DCs particularly, CD103+DCs compared to CD11b+DCs. CD103+DCs are regarded as APCs with superior capabilities to mount an effective immune response, thus understanding their homeostasis mechanism(s)/function is of paramount importance to devise effective therapeutics including DC vaccines. The Src-like adapter protein (SLAP) has been shown to dampen the signaling downstream of receptor tyrosine kinases including FLT3, cKit, and immune cell receptors including T cell receptor, B cell receptor, and Granulocyte-monocyte colony stimulating factor receptor via by recruiting c-Cbl, an ubiquitin ligase. Here, we report that SLAP deficient mice (KO) have reduced numbers of CD103+DC in lung while equal numbers in liver and kidney compared to control mice. To further confirm reduced CD103+DC in the lung, efferocytosis assays that are dependent upon CD+103 DC in lung epithelium to cleanse the apoptotic cells were performed. Flow cytometric quantification of CD103+DCs that uptake fluorescently labeled apoptotic cells administered via intranasal route and migrate to mediastinal lymph nodes confirmed reduced number of CD103+DCs in SLAP KO mice. Further analysis of DC progenitor populations showed reduced pre-DC progenitor in the lung in SLAP KO mice while bone marrow compartment showed equal progenitor populations including pre-DC and common dendritic progenitors suggesting the role of SLAP in localized FLT3 signaling in the lung. Consistently, DCs in lymphoid compartment including spleen, thymus, inguinal and popliteal lymph node did not show any defects. Upon further dissecting the cellular mechanism, SLAP KO DCs showed increased apoptosis while having similar proliferation potential in vivo at steady state.Bone marrow progenitors from SLAP KO mice failed to generate mature DCs in the presence of FLT3 ligand in vitrodue to enhanced apoptosis at early time points. Also, submaximal inhibition of FLT3 with an inhibitor, quizartinib partially rescues the apoptotic phenotype of SLAP KO bone marrow progenitors suggesting a cell-intrinsic role of SLAP in the survival of DCs. Biochemical analysis revealed that SLAP is directly recruited to the juxta-membrane residues of the FLT3 receptor in an inducible manner suggesting a direct role of SLAP in the regulation of FLT3 signaling. Phosphoflow analysis of DCs generated in the combined presence of GMCSF and FLT3 ligands showed that SLAP promotes the signaling to SHP2 while perturbs signaling to the mTOR pathway. Together these results suggest that SLAP is a critical regulator of CD103+DCs homeostasis in selective peripheral organs including the lung. Disclosures No relevant conflicts of interest to declare.

scholarly journals Role of age-related alterations of the cerebral venous circulation in the pathogenesis of vascular cognitive impairment

2019 ◽  
Vol 316 (5) ◽  
pp. H1124-H1140 ◽  
Author(s):  
Gabor A. Fulop ◽  
Stefano Tarantini ◽  
Andriy Yabluchanskiy ◽  
Andrea Molnar ◽  
Calin I. Prodan ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cerebral Arteries ◽  
Vascular Cognitive Impairment ◽  
Cerebral Veins ◽  
Older Individuals ◽  
Low Velocity ◽  
Venous Circulation ◽  
Age Related ◽  
The Brain

There has been an increasing appreciation of the role of vascular contributions to cognitive impairment and dementia (VCID) associated with old age. Strong preclinical and translational evidence links age-related dysfunction and structural alterations of the cerebral arteries, arterioles, and capillaries to the pathogenesis of many types of dementia in the elderly, including Alzheimer’s disease. The low-pressure, low-velocity, and large-volume venous circulation of the brain also plays critical roles in the maintenance of homeostasis in the central nervous system. Despite its physiological importance, the role of age-related alterations of the brain venous circulation in the pathogenesis of vascular cognitive impairment and dementia is much less understood. This overview discusses the role of cerebral veins in the pathogenesis of VCID. Pathophysiological consequences of age-related dysregulation of the cerebral venous circulation are explored, including blood-brain barrier disruption, neuroinflammation, exacerbation of neurodegeneration, development of cerebral microhemorrhages of venous origin, altered production of cerebrospinal fluid, impaired function of the glymphatics system, dysregulation of cerebral blood flow, and ischemic neuronal dysfunction and damage. Understanding the age-related functional and phenotypic alterations of the cerebral venous circulation is critical for developing new preventive, diagnostic, and therapeutic approaches to preserve brain health in older individuals.

scholarly journals Chitotriosidase: a marker and modulator of lung disease

2020 ◽  
Vol 29 (156) ◽  
pp. 190143 ◽  
Author(s):  
De Chang ◽  
Lokesh Sharma ◽  
Charles S. Dela Cruz
Keyword(s):  
Immune Response ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Bronchial Asthma ◽  
Tissue Damage ◽  
Lung Diseases ◽  
Molecular Pathogenesis ◽  
Activated Macrophages ◽  
Pulmonary Infections

Chitotriosidase (CHIT1) is a highly conserved and regulated chitinase secreted by activated macrophages; it is a member of the 18-glycosylase family (GH18). CHIT1 is the most prominent chitinase in humans, can cleave chitin and participates in the body's immune response and is associated with inflammation, infection, tissue damage and remodelling processes. Recently, CHIT1 has been reported to be involved in the molecular pathogenesis of pulmonary fibrosis, bronchial asthma, COPD and pulmonary infections, shedding new light on the role of these proteins in lung pathophysiology. The potential roles of CHIT1 in lung diseases are reviewed in this article.

A Possible Role for the Antioxidants Lutein and Zeaxanthin in Protecting against Age-Related Increases in Lens Density

Perception ◽  
1997 ◽  
Vol 26 (1_suppl) ◽  
pp. 166-166
Author(s):  
B R Hammond ◽  
J E Náñez
Keyword(s):  
Light Exposure ◽  
Latency Period ◽  
Crystalline Lens ◽  
Epidemiological Data ◽  
Protective Role ◽  
Older Individuals ◽  
Age Related ◽  
Number Of Factors ◽  
Relationship Of

Epidemiological data have identified a number of factors that influence risk of developing age-related cataract (ARC). For instance, factors that promote (eg smoking and light exposure) and factors that protect (eg antioxidants) against oxidative stress to the crystalline lens appear to increase and decrease risk of ARC, respectively. Although biochemical studies consistently support a protective role for antioxidants, the epidemiological data are inconsistent. Since ARC is a condition with a protracted latency period, it is possible that the inconsistencies present in the epidemiological literature may be due to the focus on cataractous patients. We focused on the lens health of individuals prior to cataract. Lens health was determined by measuring the optical density (OD) of the lens with a psychophysical technique. OD characterises many of the biochemical changes of the lens and is part of many systems used to classify ARC. Variance in lens OD, stratified by age, was examined for its relationship to variables thought to be important to the etiology of ARC. We report results for the relationship of lens OD to the antioxidants lutein and zeaxanthin (L and Z). For older individuals (>48 years) we noted a significant inverse relationship between dietary intake of L and Z and lens OD ( n=39, r=−0.34, p<0.015). This was not the case for younger individuals (24 – 36 years). This relationship is increased when L and Z are measured directly in the retina is a psychophysical technique. For older individuals, retinal L and Z (ie macular pigment) are inversely related to lens OD ( n=51, r=-0.47, p<0.001). These data are consistent with a role of L and Z in protecting against age-related increases in the OD of the crystalline lens.

Role of estrogen in the management of COVID – 19 in females

2020 ◽  
Vol 10 (3) ◽  
pp. 67-70
Author(s):  
Keerthi Chadam Venkatesulu ◽  
Shaik Habeeb Jan ◽  
Harika Sree Gaddam
Keyword(s):  
Health Care Systems ◽  
Treatment Options ◽  
Adverse Outcomes ◽  
Older Individuals ◽  
Therapeutic Benefits ◽  
Age Related ◽  
Disease Condition ◽  
Care Systems ◽  
The Difference

With the increase, the spread of COVID-19 its effect can be seen on health care systems seek innovative treatment ways as the need of the hour. The suspected leading cause of COVID-19 is due to the response to inflammations and the cytokine storm, which majorly damages the lung tissue. The difference in response to the vaccine can be seen due to different sex. Moreover, age-related decrease in sex steroid hormones like Estrogen as well as testosterone can promote pro-inflammatory raise in older individuals which in turn increases the risk of COVID-19 related adverse outcomes. Such sex hormones have the capacity of mitigating inflammatory response and can also provide promising therapeutic benefits for patients suffering from COVID-19. Moreover, over above the effects of on any ERS, these drugs showed useful ancillary properties. Most showed to highlight broader roles in mitigating viral replication by the ER-independent mechanisms as mentioned. Data simplifies ER modulation an apt pharmacological approach for restricting storm and thus prevents the inflammation due to COVID-19. Mainly the application of or tissue-selective estrogen complex can provide a pharmacological response. Such treatment options can be fruitful for both sexes in the early phase of such disease condition to prevent further progression of the disease to severe forms.

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