scholarly journals Protein Posttranslational Modifications: Roles in Aging and Age-Related Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-19 ◽  
Author(s):  
Ana L. Santos ◽  
Ariel B. Lindner
Keyword(s):  
Posttranslational Modifications ◽  
Molecular Mechanisms ◽  
Molecular Processes ◽  
Progressive Decline ◽  
Age Related ◽  
Evolutionarily Conserved ◽  
Protein Posttranslational Modifications ◽  
Aging Models ◽  
The Relationship

Aging is characterized by the progressive decline of biochemical and physiological function in an individual. Consequently, aging is a major risk factor for diseases like cancer, obesity, and type 2 diabetes. The cellular and molecular mechanisms of aging are not well understood, nor is the relationship between aging and the onset of diseases. One of the hallmarks of aging is a decrease in cellular proteome homeostasis, allowing abnormal proteins to accumulate. This phenomenon is observed in both eukaryotes and prokaryotes, suggesting that the underlying molecular processes are evolutionarily conserved. Similar protein aggregation occurs in the pathogenesis of diseases like Alzheimer’s and Parkinson’s. Further, protein posttranslational modifications (PTMs), either spontaneous or physiological/pathological, are emerging as important markers of aging and aging-related diseases, though clear causality has not yet been firmly established. This review presents an overview of the interplay of PTMs in aging-associated molecular processes in eukaryotic aging models. Understanding PTM roles in aging could facilitate targeted therapies or interventions for age-related diseases. In addition, the study of PTMs in prokaryotes is highlighted, revealing the potential of simple prokaryotic models to uncover complex aging-associated molecular processes in the emerging field of microbiogerontology.

scholarly journals Natural Compounds and Aging: Between Autophagy and Inflammasome

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Shih-Yi Chuang ◽  
Chih-Hung Lin ◽  
Jia-You Fang
Keyword(s):  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Natural Compounds ◽  
Inflammasome Activation ◽  
Defense Systems ◽  
Age Related ◽  
Nlrp3 Inflammasome Activation ◽  
The Relationship ◽  
Different Sources

Aging, a natural physiological process, is characterized by a progressive loss of physiological integrity. Loss of cellular homeostasis in the aging process results from different sources, including changes in genes, cell imbalance, and dysregulation of the host-defense systems. Innate immunity dysfunctions during aging are connected with several human pathologies, including metabolic disorders and cardiovascular diseases. Recent studies have clearly indicated that the decline in autophagic capacity that accompanies aging results in the accumulation of dysfunctional mitochondria, reactive oxygen species (ROS) production, and further process dysfunction of the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome activation in the macrophages, which produce the proinflammatory cytokines. These factors impair cellular housekeeping and expose cells to higher risk in many age-related diseases, such as atherosclerosis and type 2 diabetes. In this review, we investigated the relationship between dysregulation of the inflammasome activation and perturbed autophagy with aging as well as the possible molecular mechanisms. We also summarized the natural compounds from food intake, which have potential to reduce the inflammasome activation and enhance autophagy and can further improve the age-related diseases discussed in this paper.

scholarly journals Drusen Characteristics of Type 2 Macular Neovascularization in Age-related Macular Degeneration

2020 ◽  
Author(s):  
Daniel Ahmed ◽  
Martin Stattin ◽  
Anna-Maria Haas ◽  
Alexandra Graf ◽  
Katharina Krepler ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Care Center ◽  
Age Related Macular Degeneration ◽  
Retrospective Data Analysis ◽  
Age Related ◽  
The Relationship ◽  
Subretinal Drusenoid Deposits ◽  
Medical Retina ◽  
Fellow Eyes

Abstract Background: To assess the relationship between drusen characteristics and type 2 macular neovascularization (MNV) in age-related macular degeneration (AMD)Methods: Retrospective data analysis of eyes previously diagnosed with neovascular AMD in a tertiary eye care center (Medical Retina Unit, Rudolf Foundation Hospital, Vienna, Austria) between June 2008 and December 2017. Drusen subtypes, fibrosis, atrophy and subfoveal choroidal thickness (SFCT) of both eyes in patients with type 2 MNV lesions were categorized based on multimodal imaging.Results: Type 2 MNV was diagnosed in 27 (3.2%) of 835 eyes (749 patients). Drusen characteristics in type 2 MNV were observed as followed: drusen < 63 mm in 2 eyes (7.4%), drusen ≥ 63 mm in 10 eyes (37%), subretinal drusenoid deposits (SDD) in 8 eyes (29.6%), cuticular drusen in 2 eye (7.4%) and no drusen were evident in 10 eyes (37%). Drusen distribution in 23 fellow eyes was detected as followed: drusen < 63 mm in 2 eyes (8.7%), drusen ≥ 63 mm in 9 eyes (39.1%), SDD in 5 eyes (21.7%), cuticular drusen in 1 eye (4.3%) and no drusen were evident in 9 eyes (39.1%). Mean SFCT was 140 ± 49 mm in affected eyes and 152 ± 41 mm in the fellow eyes. Patients with drusen or SDD were significantly younger (mean 70.88 ± 6.85, p=0.04) than patients without deposits (mean 77.40 ± 5.74). Conclusions: Type 2 MNV remains a rare entity in AMD. It was frequently seen in the absence ofdrusen, a hallmark of AMD. These findings contribute to the heterogeneity of phenotypes related to pure type 2 lesions.

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 Obesity and inflammatory skin diseases

2019 ◽  
Vol 3 (1) ◽  
pp. 50
Author(s):  
Satoshi Nakamizo ◽  
Tetsuya Honda ◽  
Kenji Kabashima
Keyword(s):  
Molecular Mechanisms ◽  
Skin Diseases ◽  
Public Health Problem ◽  
Inflammatory Skin Diseases ◽  
Significant Public Health Problem ◽  
Significant Public Health ◽  
Inflammatory Skin ◽  
Underlying Mechanisms ◽  
The Relationship

Obesity has become a significant public health problem since it may cause many chronic diseases, including type 2 diabetes, cardiovascular diseases, liver diseases, and some cancers. Recent studies have shown that obesity is a major risk factor for the development of inflammatory skin diseases, including eczema, atopic dermatitis, and psoriasis. Inflammatory cytokines produced from adipose tissue and activation of innate immunity are considered as important factors in obesity-induced inflammation. However, the molecular mechanisms by which obesity affects the development of inflammatory skin diseases are not well understood. In this review, we will discuss the relationship between the underlying mechanisms linking obesity and inflammatory skin diseases based on the latest researches.

scholarly journals The immunosenescence and lipotoxicity in thyrotoxicosis mice

2022 ◽  
Author(s):  
Qin Feng
Keyword(s):  
Elderly Patients ◽  
Accelerated Aging ◽  
Cholesterol Levels ◽  
Age Related ◽  
Ifn Γ ◽  
Aging Models ◽  
High Level ◽  
The Relationship ◽  
Worse Prognosis ◽  
Biochemical Examination

Abstract COVID-19 is a worldwide outbreak now, and it is found to be age-related. Immunosenescence may be a predisposing and severe factor for COVID-19. Besides, many infectious diseases in clinic are age-related, and elderly patients have longer hospitalization and worse prognosis. Therefore, finding suitable aging models is of great significance for fighting aging related diseases and promoting the prognosis of elderly patients. In this study, the relationship between thyrotoxicosis and aging was investigated by routine detection and serum metabonomics in mice. The results of routine blood test and flow cytometry showed significant decrease in neutrophils, lymphocytes, CD4+/CD8+ and CD4+IFN-γ + lymphocytes in thyrotoxicosis mice. Biochemical examination combined with serum metabolomics analysis showed that serious disorder of lipid metabolism may be one of the causes of immunosenescence, including lower cholesterol levels, lower levels of VD and bile acids, high level of glucocorticoids, triglycerides, free fatty acids, Sphingolipids and decrease of Docosanoids, especially DPA. This study proves that thyrotoxicosis mice are an accelerated aging model. In present study, the main performance is immunosenescence, which may be due to lipotoxicity, suggesting that the immunosenescence state can be adjusted by improving lipotoxicity, whether anti thyroxine or not. However, there are other manifestations of thyroid toxicity mouse model simulating aging, such as organ aging, which need to continue to be studied by means of system biology to provide more comprehensive evidence.

scholarly journals ROLE OF INSULIN IN BRAIN: DELVE INTO THE MOLECULAR MECHANISMS

2021 ◽  
Author(s):  
Sofia Khanam
Keyword(s):  
Molecular Mechanisms ◽  
Insulin Signalling ◽  
Diabetic Patients ◽  
Functional Activities ◽  
Mitochondrial Alterations ◽  
Age Related ◽  
The Brain ◽  
And Oxidative Stress

We have learned over the last several decades that the brain is an important target for insulin action. In central nervous system (CNS) it mainly affects feeding behaviour and various aspects of memory and cognition. Insulin signalling in CNS has emerged as a novel field of research since decreases brain insulin levels and signalling were associated to impaired learning, memory and age-related neurodegenerative diseases. Alterations of these functional activities may contribute to the manifestation of several clinical entities, such as central insulin resistance, type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD). A close alliance between T2DM and AD has been reported, to the extent that AD is twice more frequent in diabetic patients. There are links between T2DM and AD through mitochondrial alterations and oxidative stress, altered energy and glucose metabolism, cholesterol modifications, dysfunctional protein O-GlcNAcylation, formation of amyloid plaques, altered Aβ metabolism and tau hyperphosphorylation. Herewith, we aim to integrate the metabolic, neuromodulatory, and neuroprotective roles of insulin in two age-related pathologies: T2DM and AD, both in terms of intracellular signalling and potential therapeutic approach.

scholarly journals Chondrocyte Aging: The Molecular Determinants and Therapeutic Opportunities

2021 ◽  
Vol 9 ◽  
Author(s):  
Thamil Selvee Ramasamy ◽  
Yong Mei Yee ◽  
Ilyas M. Khan
Keyword(s):  
Molecular Mechanisms ◽  
Articular Chondrocytes ◽  
Functional Decline ◽  
Cellular Aging ◽  
Joint Degeneration ◽  
Complex Interplay ◽  
Regenerative Capacity ◽  
Progressive Decline ◽  
Age Related ◽  
Molecular Determinants

Osteoarthritis (OA) is a joint degenerative disease that is an exceedingly common problem associated with aging. Aging is the principal risk factor for OA, but damage-related physiopathology of articular chondrocytes probably drives the mechanisms of joint degeneration by a progressive decline in the homeostatic and regenerative capacity of cells. Cellular aging is the manifestation of a complex interplay of cellular and molecular pathways underpinned by transcriptional, translational, and epigenetic mechanisms and niche factors, and unraveling this complexity will improve our understanding of underlying molecular changes that affect the ability of the articular cartilage to maintain or regenerate itself. This insight is imperative for developing new cell and drug therapies for OA disease that will target the specific causes of age-related functional decline. This review explores the key age-related changes within articular chondrocytes and discusses the molecular mechanisms that are commonly perturbed as cartilage ages and degenerates. Current efforts and emerging potential therapies in treating OA that are being employed to halt or decelerate the aging processes are also discussed.

scholarly journals High Reflectivity and Low Reflectivity Properties on OCTA Influence the Detection of Macular Neovascularization in AMD

2021 ◽  
Vol 9 ◽  
Author(s):  
Alessandro Arrigo ◽  
Emanuela Aragona ◽  
Alessandro Bordato ◽  
Alessia Amato ◽  
Andrea Saladino ◽  
...  
Keyword(s):  
Blood Flow ◽  
Age Related Macular Degeneration ◽  
Cross Sectional ◽  
High Reflectivity ◽  
Age Related ◽  
Flow Features ◽  
The Relationship ◽  
Good Agreement

Background: In this study, we aimed to discriminate high reflectivity and low reflectivity macular neovascularization (MNV) lesions secondary to age-related macular degeneration (AMD)and to assess the influence of blood flow features on the amount of MNV detected by optical coherence tomography angiography (OCTA).Methods: The study was designed as observational, cross-sectional. Type 1 and type 2 MNV lesions were included. All the patients underwent fluorescein angiography (FA), indocyanine green angiography (ICGA) and OCTA. MNV size was calculated on early FA for type 2 MNV and on both early and late phases of ICGA for type 1 lesions. From OCTA, we calculated both MNV size and MNV reflectivity. We assessed the agreement between FA/ICGA and OCTA MNV sizes. Moreover, we studied the relationship between MNV reflectivity properties and MNV OCTA detection.Results: Fifty eyes (50 patients) were included. MNV was identified as follows: 35 /70%) type 1 and 15 (30%) type 2. We found a good agreement between early ICGA size and OCTA size for type 1 MNV (2.10 ± 1.91 mm2 vs 2.09 ± 1.87 mm2; p &gt; 0.05), whereas MNV lesions turned out to be remarkably bigger on late ICGA phase (3.41 ± 2.87 mm2; p &lt; 0.01). Interestingly, OCTA well-matched with FA in terms of MNV size for type 2 lesions (2.36 ± 2.15 mm2 vs 2.37 ± 2.25 mm2). MNV reflectivity was higher in type 2 MNV and it was strongly associated with the OCTA ability to reconstruct the neovascular network.Conclusion: Our study quantitatively showed that MNV filling pattern and MNV blood flow reflectivity features influence the OCTA detection of the MNV in its entirety.

scholarly journals Drusen Characteristics of Type 2 Macular Neovascularization in Age-related Macular Degeneration

2019 ◽  
Author(s):  
Daniel Ahmed ◽  
Martin Stattin ◽  
Anna-Maria Haas ◽  
Alexandra Graf ◽  
Katharina Krepler ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Care Center ◽  
Age Related Macular Degeneration ◽  
Retrospective Data Analysis ◽  
Age Related ◽  
Imaging Results ◽  
The Relationship ◽  
Subretinal Drusenoid Deposits ◽  
Fellow Eyes

Abstract Background To assess the relationship between drusen characteristics and type 2 macular neovascularization (MNV) in age-related macular degeneration (AMD). Methods Retrospective data analysis of eyes previously diagnosed with neovascular AMD in a tertiary eye care center (Medical Retina Unit, Rudolf Foundation Hospital, Vienna, Austria) between June 2008 and December 2017. Drusen subtypes, fibrosis, atrophy and subfoveal choroidal thickness (SFCT) of both eyes in patients with type 2 MNV lesions were categorized based on multimodal imaging. Results Type 2 MNV was diagnosed in 27 (3.2%) of 835 eyes (749 patients). Drusen characteristics in type 2 MNV were observed as followed: drusen < 63 m in 2 eyes (7.4%), drusen ≥ 63 mm in 10 eyes (37%), subretinal drusenoid deposits (SDD) in 8 eyes (29.6%), cuticular drusen in 2 eye (7.4%) and no drusen were evident in 10 eyes (37%). Drusen distribution in 23 fellow eyes was detected as followed: drusen < 63 mm in 2 eyes (8.7%), drusen ≥ 63 mm in 9 eyes (39.1%), SDD in 5 eyes (21.7%), cuticular drusen in 1 eye (4.3%) and no drusen were evident in 8 eyes (34.8%). Mean SFCT was 140 ± 49 mm in affected eyes and 152 ± 41 mm in the fellow eyes. Conclusions Type 2 MNV remains a rare entity in AMD. It was frequently seen in the absence of drusen, a hallmark of AMD. These findings suggest other biological pathways related to pure type 2 lesions.

scholarly journals Drusen Characteristics of Type 2 Macular Neovascularization in Age-related Macular Degeneration

2020 ◽  
Author(s):  
Daniel Ahmed ◽  
Martin Stattin ◽  
Anna-Maria Haas ◽  
Alexandra Graf ◽  
Katharina Krepler ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Care Center ◽  
Age Related Macular Degeneration ◽  
Retrospective Data Analysis ◽  
Age Related ◽  
Imaging Results ◽  
The Relationship ◽  
Subretinal Drusenoid Deposits ◽  
Fellow Eyes

Abstract Background To assess the relationship between drusen characteristics and type 2 macular neovascularization (MNV) in age-related macular degeneration (AMD) Methods Retrospective data analysis of eyes previously diagnosed with neovascular AMD in a tertiary eye care center (Medical Retina Unit, Rudolf Foundation Hospital, Vienna, Austria) between June 2008 and December 2017. Drusen subtypes, fibrosis, atrophy and subfoveal choroidal thickness (SFCT) of both eyes in patients with type 2 MNV lesions were categorized based on multimodal imaging. Results Type 2 MNV was diagnosed in 27 (3.2%) of 835 eyes (749 patients). Drusen characteristics in type 2 MNV were observed as followed: drusen < 63 mm in 2 eyes (7.4%), drusen ≥ 63 mm in 10 eyes (37%), subretinal drusenoid deposits (SDD) in 8 eyes (29.6%), cuticular drusen in 2 eye (7.4%) and no drusen were evident in 10 eyes (37%). Drusen distribution in 23 fellow eyes was detected as followed: drusen < 63 mm in 2 eyes (8.7%), drusen ≥ 63 mm in 9 eyes (39.1%), SDD in 5 eyes (21.7%), cuticular drusen in 1 eye (4.3%) and no drusen were evident in 9 eyes (39.1%). Mean SFCT was 140 ± 49 mm in affected eyes and 152 ± 41 mm in the fellow eyes. Patients with drusen or SDD were significantly younger (mean 70.88 ± 6.85, p=0.04) than patients without deposits (mean 77.40 ± 5.74). Conclusions Type 2 MNV remains a rare entity in AMD. It was frequently seen in the absence of drusen, a hallmark of AMD. These findings contribute to the heterogeneity of phenotypes related to pure type 2 lesions.

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