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.

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.

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 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 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.

scholarly journals Immunosenescence of Polymorphonuclear Neutrophils

2010 ◽  
Vol 10 ◽  
pp. 145-160 ◽  
Author(s):  
Inga Wessels ◽  
Judith Jansen ◽  
Lothar Rink ◽  
Peter Uciechowski
Keyword(s):  
Molecular Mechanisms ◽  
Adaptive Immune System ◽  
The Elderly ◽  
Polymorphonuclear Neutrophils ◽  
Traditional Role ◽  
Functional Changes ◽  
The Public ◽  
Age Related

All immune cells are affected by aging, contributing to the high susceptibility to infections and increased mortality observed in the elderly. The effect of aging on cells of the adaptive immune system is well documented. In contrast, knowledge concerning age-related defects of polymorphonuclear neutrophils (PMN) is limited. During the past decade, it has become evident that in addition to their traditional role as phagocytes, neutrophils are able to secrete a wide array of immunomodulating molecules. Their importance is underlined by the finding that genetic defects that lead to neutropenia increase susceptibility to infections. Whereas there is consistence about the constant circulating number of PMN throughout aging, the abilities of tissue infiltration, phagocytosis, and oxidative burst of PMN from aged donors are discussed controversially. Furthermore, there are numerous discrepancies betweenin vivoandin vitroresults, as well as between results for murine and human PMN. Most of the reported functional changes can be explained by defective signaling pathways, but further research is required to get a detailed insight into the underlying molecular mechanisms. This could form the basis for drug development in order to prevent or treat age-related diseases, and thus to unburden the public health systems.

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.

Age-associated (cardio)metabolic diseases and cross-talk between adipose tissue and skeleton: endocrine aspects

2014 ◽  
Vol 20 (1) ◽  
Author(s):  
Silvia Migliaccio ◽  
Emanuela A. Greco ◽  
Antonio Aversa ◽  
Andrea Lenzi
Keyword(s):  
Cardiovascular Diseases ◽  
Muscle Mass ◽  
Fat Mass ◽  
Successful Aging ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
The Elderly ◽  
Mortality And Morbidity ◽  
Age Related ◽  
Age Related Changes

AbstractAged individuals continue to increase in number, and it is important to understand the pathophysiological mechanisms of age-related changes in order to develop interventions that could contribute to “successful aging”. Metabolic and hormonal factors, age-related changes in body composition, and a decline in physical activity are all involved in the tendency to lose muscle mass, to gain fat mass, and, also, to experience bone loss. Obesity, sarcopenia, and osteoporosis are important widespread health problems that lead to high prevalence of both mortality and morbidity. Indeed, during the last decades, obesity and osteoporosis have become a major health threat around the world. Aging increases the risk of developing obesity, sarcopenia, osteoporosis, and, also, cardiovascular diseases. A reduction of both bone and muscle mass with a corresponding increase of fat mass and inflammation and hormonal imbalance in the elderly lead to and may synergistically increase cardiovascular diseases. This review will focus on the relationship among these different medical situations, trying to clarify the cellular and molecular mechanisms.

scholarly journals Oxidative Stress, Mitochondrial Dysfunction, and Aging

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Hang Cui ◽  
Yahui Kong ◽  
Hong Zhang
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Mitochondrial Dna ◽  
Molecular Mechanisms ◽  
Ros Production ◽  
Oxygen Species ◽  
Progressive Decline ◽  
Theories Of Aging ◽  
Age Related ◽  
Potential Impact

Aging is an intricate phenomenon characterized by progressive decline in physiological functions and increase in mortality that is often accompanied by many pathological diseases. Although aging is almost universally conserved among all organisms, the underlying molecular mechanisms of aging remain largely elusive. Many theories of aging have been proposed, including the free-radical and mitochondrial theories of aging. Both theories speculate that cumulative damage to mitochondria and mitochondrial DNA (mtDNA) caused by reactive oxygen species (ROS) is one of the causes of aging. Oxidative damage affects replication and transcription of mtDNA and results in a decline in mitochondrial function which in turn leads to enhanced ROS production and further damage to mtDNA. In this paper, we will present the current understanding of the interplay between ROS and mitochondria and will discuss their potential impact on aging and age-related diseases.

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