scholarly journals Hereditary syndromes with signs of premature aging

2020 ◽  
Vol 22 (3) ◽  
pp. 4-18
Author(s):  
Olga O. Golounina ◽  
Valentin V. Fadeev ◽  
Zhanna E. Belaya
Keyword(s):  
Molecular Mechanisms ◽  
Werner Syndrome ◽  
Accelerated Aging ◽  
Scientific Data ◽  
The Body ◽  
Premature Aging ◽  
Hereditary Diseases ◽  
Age Related ◽  
Progeroid Syndromes ◽  
Age Related Changes

Aging is a multi-factor biological process that inevitably affects everyone. Degenerative processes, starting at the cellular and molecular levels, gradually influence the change in the functional capabilities of all organs and systems. Progeroid syndromes (from Greek. progērōs prematurely old), or premature aging syndromes, represent clinically and genetically heterogeneous group of rare hereditary diseases characterized by accelerated aging of the body. Progeria and segmental progeroid syndromes include more than a dozen diseases, but the most clear signs of premature aging are evident in Hutchinson-Guilford Progeria Syndrome and Werner Syndrome. This review summarizes the latest scientific data reflecting the etiology and clinical picture of progeria and segmental progeroid syndromes in humans. Molecular mechanisms of aging are considered, using the example of progeroid syndromes. Modern possibilities and potential ways of influencing the mechanisms of the development of age-related changes are discussed. Further study of genetic causes, as well as the development of treatment for progeria and segmental progeroid syndromes, may be a promising direction for correcting age-related changes and increasing life expectancy.

scholarly journals Altered Nuclear Functions in Progeroid Syndromes: a Paradigm for Aging Research

2009 ◽  
Vol 9 ◽  
pp. 1449-1462 ◽  
Author(s):  
Baomin Li ◽  
Sonali Jog ◽  
Jose Candelario ◽  
Sita Reddy ◽  
Lucio Comai
Keyword(s):  
Werner Syndrome ◽  
Accelerated Aging ◽  
Natural Aging ◽  
Aging Research ◽  
Cellular Processes ◽  
Functional Connections ◽  
Age Related ◽  
Progeroid Syndromes ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

Syndromes of accelerated aging could provide an entry point for identifying and dissecting the cellular pathways that are involved in the development of age-related pathologies in the general population. However, their usefulness for aging research has been controversial, as it has been argued that these diseases do not faithfully reflect the process of natural aging. Here we review recent findings on the molecular basis of two progeroid diseases, Werner syndrome (WS) and Hutchinson-Gilford progeria syndrome (HGPS), and highlight functional connections to cellular processes that may contribute to normal aging.

Potential Possibilities of Nuclear Medicine Methods in Diagnostics Age Changes of the Cardiovascular System.

2021 ◽  
Vol 66 (5) ◽  
pp. 59-65
Author(s):  
M. Vorontsova ◽  
A. Obrezan ◽  
A. Obrezan
Keyword(s):  
Aging Process ◽  
Molecular Mechanisms ◽  
The Body ◽  
Premature Aging ◽  
Diagnostic Methods ◽  
Age Changes ◽  
Medical Interventions ◽  
Defense Systems ◽  
Age Related ◽  
Daunting Task

In connection with the increase in the average age of the world's population, the problem of preventing premature aging and the treatment of age-related diseases is coming to the fore. The main direction in the implementation of this goal is to influence the key molecular mechanisms of aging in order to suppress pathological processes and activate the defense systems of the cell and the body as a whole. In order to solve this daunting task, it is necessary to have in the arsenal not only various means of intervention in the aging process, but also diagnostic methods that would allow to fully verify these processes and evaluate the effectiveness of medical interventions.

scholarly journals Molecular Mechanisms Underlying Accelerated Aging by Defects in the FGF23-Klotho System

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Makoto Kuro-o
Keyword(s):  
Molecular Mechanisms ◽  
Accelerated Aging ◽  
Basic Research ◽  
Cellular Level ◽  
Premature Aging ◽  
Health Span ◽  
Aging Society ◽  
Age Related ◽  
Evolutionarily Conserved ◽  
Premature Aging Syndrome

The basic research of aging has been primarily focused on elucidating mechanisms of aging and longevity that are evolutionarily conserved from yeasts to primates. Such efforts have culminated in the notion that (1) senescence at the cellular level is associated with aging at the organismal level and that (2) calorie restriction and growth suppression decelerate aging. However, these important findings in the basic research have not necessarily been linked to improvement of daily medical practice in the aging society. It has become increasingly important to investigate mechanisms of aging unique to mammals or humans and apply the research fruits for the treatment of major age-related disorders to extend the health span. Seminal studies on the klotho mouse, a mutant exhibiting a premature aging syndrome, have identified phosphate as a proaging factor in mammals. In this review, mechanisms of phosphate-induced premature aging and potential therapeutic targets will be discussed, which may be directly applicable for developing novel strategies for the treatment of chronic kidney disease and its complications.

scholarly journals Age-Related Changes in Molecular and Whole Muscle Function: Role of Fat Content?

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 141-141
Author(s):  
Joseph Gordon III ◽  
Nicholas Remillard ◽  
Chad Straight ◽  
Rajakumar Nagarajan ◽  
Bruce Damon ◽  
...  
Keyword(s):  
Older Adults ◽  
Molecular Mechanisms ◽  
Fat Content ◽  
Fat Deposition ◽  
Muscle Size ◽  
Type I ◽  
Contraction Velocity ◽  
Age Related ◽  
Whole Muscle ◽  
Age Related Changes

Abstract Decreases in muscle size and function are a general consequence of old age; the precise mechanisms of these changes remain unclear. Recent studies suggest that fat deposition in muscle may also contribute to dysfunction in older adults. Fat content was quantified in the quadriceps, and its effects on function in healthy young (21-45 y) and older (65-75 y) men and women (n=44) of comparable physical activity were compared. A subset of the young matched with the older group for muscle fat content were also examined. Peak fat-free whole muscle cross-sectional area (mCSA; cm2), volume (MV; cm3), fat content (fat fraction, FF; %), specific torque (Nm/mCSA) and peak contraction velocity (Nm∙s-1) were determined using fat-water magnetic resonance imaging and dynamometry (0-300□∙s-1). To examine potential molecular mechanisms of muscle weakness, vastus lateralis biopsies were obtained (n=31) and cross-bridge kinetics of type I and II fibers were determined. FF was higher in older adults than young (8.4±1.2% (SE), 7.6±1.4; p=0.03), while mCSA (48.9±10.4 vs. 64.2±17.3), MV (1536±532 vs. 2112±708), specific torque (2.6±0.4 vs. 3.2±0.4), and peak voluntary contraction velocity (422±20 vs. 441±23) were lower in older than young (p<0.01). Type II fiber myosin attachment rate was slower and attachment time longer in older muscle (p<0.017), providing a potential mechanism for the slowing of peak contraction velocity with age. Notably, differences at the whole muscle and molecular levels remained for the subset of young and older groups matched for FF, suggesting that fat deposition in muscle does not exacerbate age-related changes in function.

scholarly journals NAD+Metabolism in Aging and Cancer

2019 ◽  
Vol 3 (1) ◽  
pp. 105-130 ◽  
Author(s):  
Tyler G. Demarest ◽  
Mansi Babbar ◽  
Mustafa N. Okur ◽  
Xiuli Dan ◽  
Deborah L. Croteau ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Redox Homeostasis ◽  
Accelerated Aging ◽  
Cancer Therapies ◽  
Nad Metabolism ◽  
Cellular Processes ◽  
Cancer Pathogenesis ◽  
Nicotinamide Mononucleotide ◽  
Age Related

Aging is a major risk factor for many types of cancer, and the molecular mechanisms implicated in aging, progeria syndromes, and cancer pathogenesis display considerable similarities. Maintaining redox homeostasis, efficient signal transduction, and mitochondrial metabolism is essential for genome integrity and for preventing progression to cellular senescence or tumorigenesis. NAD+is a central signaling molecule involved in these and other cellular processes implicated in age-related diseases and cancer. Growing evidence implicates NAD+decline as a major feature of accelerated aging progeria syndromes and normal aging. Administration of NAD+precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) offer promising therapeutic strategies to improve health, progeria comorbidities, and cancer therapies. This review summarizes insights from the study of aging and progeria syndromes and discusses the implications and therapeutic potential of the underlying molecular mechanisms involved in aging and how they may contribute to tumorigenesis.

scholarly journals Potential Treatment of Retinal Diseases with Iron Chelators

2018 ◽  
Vol 11 (4) ◽  
pp. 112 ◽  
Author(s):  
Wanting Shu ◽  
Joshua Dunaief
Keyword(s):  
Retinal Degeneration ◽  
Therapeutic Potential ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Body ◽  
Age Related Macular Degeneration ◽  
Hereditary Diseases ◽  
Iron Chelators ◽  
Excess Iron ◽  
Age Related

Iron is essential for life, while excess iron can be toxic. Iron generates hydroxyl radical, which is the most reactive free radical, causing oxidative stress. Since iron is absorbed through the diet but not excreted from the body, it accumulates with age in tissues, including the retina, consequently leading to age-related toxicity. This accumulation is further promoted by inflammation. Hereditary diseases such as aceruloplasminemia, Friedreich’s ataxia, pantothenate kinase-associated neurodegeneration, and posterior column ataxia with retinitis pigmentosa involve retinal degeneration associated with iron dysregulation. In addition to hereditary causes, dietary or parenteral iron supplementation has been recently reported to elevate iron levels in the retinal pigment epithelium (RPE) and promote retinal degeneration. Ocular siderosis from intraocular foreign bodies or subretinal hemorrhage can also lead to retinopathy. Evidence from mice and humans suggests that iron toxicity may contribute to age-related macular degeneration pathogenesis. Iron chelators can protect photoreceptors and RPE in various mouse models. The therapeutic potential for iron chelators is under investigation.

Age-related changes in erythrocyte agglutinability in Hiroshima subjects

1961 ◽  
Vol 16 (6) ◽  
pp. 1093-1096
Author(s):  
J. W. Hollingsworth ◽  
H. B. Hamilton ◽  
G. Ishii
Keyword(s):  
Blood Group ◽  
Technical Assistance ◽  
Atomic Bomb ◽  
Accelerated Aging ◽  
The Third ◽  
Age Related ◽  
Group A ◽  
Age Related Changes

As part of a physiologic aging assessment in survivors of the atomic bombing, agglutinability of erythrocytes with A and B antisera was studied in 1,495 subjects in Hiroshima. It was found that erythrocyte agglutinability is maximal during the third decade and falls progressively with advancing years. At age 20—40, agglutinability of erythrocytes from females was somewhat less than that of males. Subjects of blood group AB demonstrated agglutinability titers with both antisera comparable to the titers of the group A and B subjects. Analysis of agglutinability titers in relationship to degree of irradiation from the Hiroshima atomic bomb in 1945 failed to show differences, but the sample was too small to allow definite conclusions about possible radiation-accelerated aging. Note: With the Technical Assistance of N. Ueda Submitted on February 16, 1961

scholarly journals P0018GLOMERULAR ENDOTHELIAL CELL SENESCENCE DRIVES AGE-RELATED KIDNEY DISEASE THROUGH PAI-1

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Camille Cohen ◽  
Legoff Oceanc ◽  
Frederic Soysouvanh ◽  
Marine Tanou ◽  
Florence Vasseur ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Kidney Disease ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Accelerated Aging ◽  
Plasminogen Activator Inhibitor 1 ◽  
Histological Lesion ◽  
Glomerular Endothelial Cells ◽  
Age Related ◽  
Pai 1

Abstract Background and Aims In age-related chronic kidney disease (CKD), the most frequent histological lesion observed is glomerulosclerosis. The molecular mechanisms involved in this deterioration process are unclear, but cellular senescence might play a role. Method By combining several murine models of physiological and accelerated aging with transgenic animals and in vitro models, we discovered the role of endothelial senescence in the development of glomerular lesions. Results These senescent glomerular endothelial cells secreted several molecules, grouped under the senescence associated secretory phenotype (SASP) including the plasminogen activator inhibitor 1 (PAI-1). Specific deletion of PAI-1 in endothelial cells prevented the development of glomerulosclerosis during physiological and accelerated aging, by decreasing podocyte loss. In addition, we showed that PAI-1 mediates a detrimental endothelial-podocyte crosstalk, as incubation of podocytes by supernatant of senescent glomerular endothelial cells led to their detachment. Consistently, preincubation of the senescent supernatant with tiplaxtinin, a PAI-1 inhibitor, preserved podocytes. More importantly, we demonstrated that these data are relevant to humans. In fact, PAI-1 staining the day of the transplantation was predictive of kidney allograft dysfunction 12 months after transplantation from elderly donors. Conclusion In conclusion, our study uncovers the critical role played by endothelial senescence in the development of glomerulosclerosis during aging and identified PAI-1 as a novel promising biomarker for predicting kidney dysfunction in patients receiving a kidney from elderly donors.

A genome-wide CRISPR-based screen identifies KAT7 as a driver of cellular senescence

2021 ◽  
Vol 13 (575) ◽  
pp. eabd2655
Author(s):  
Wei Wang ◽  
Yuxuan Zheng ◽  
Shuhui Sun ◽  
Wei Li ◽  
Moshi Song ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Werner Syndrome ◽  
Embryonic Stem ◽  
Accelerated Aging ◽  
Premature Aging ◽  
Mesenchymal Precursor Cells ◽  
Genome Wide ◽  
A Genome ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

Understanding the genetic and epigenetic bases of cellular senescence is instrumental in developing interventions to slow aging. We performed genome-wide CRISPR-Cas9–based screens using two types of human mesenchymal precursor cells (hMPCs) exhibiting accelerated senescence. The hMPCs were derived from human embryonic stem cells carrying the pathogenic mutations that cause the accelerated aging diseases Werner syndrome and Hutchinson-Gilford progeria syndrome. Genes whose deficiency alleviated cellular senescence were identified, including KAT7, a histone acetyltransferase, which ranked as a top hit in both progeroid hMPC models. Inactivation of KAT7 decreased histone H3 lysine 14 acetylation, repressed p15INK4b transcription, and alleviated hMPC senescence. Moreover, lentiviral vectors encoding Cas9/sg-Kat7, given intravenously, alleviated hepatocyte senescence and liver aging and extended life span in physiologically aged mice as well as progeroid Zmpste24−/− mice that exhibit a premature aging phenotype. CRISPR-Cas9–based genetic screening is a robust method for systematically uncovering senescence genes such as KAT7, which may represent a therapeutic target for developing aging interventions.

scholarly journals Age Related Changes in Weight of the Thymus Gland of Bangladeshi People

1970 ◽  
Vol 8 (1) ◽  
pp. 10-12
Author(s):  
Meherunnessa Begum ◽  
Uttam Kumar Paul ◽  
Md Jahangir Alam
Keyword(s):  
Related Problem ◽  
Immune Status ◽  
Regulatory Mechanism ◽  
Age Groups ◽  
The Body ◽  
Thymus Gland ◽  
Thymus Weight ◽  
Age Related ◽  
Key Words Thymus ◽  
Age Related Changes

Context: Thymus is intimately related to the immuno regulatory mechanism of the body, its weight in general as well as at different age in a particular population might also be related to the overall immune status of that population. Thus the knowledge of the weight of the thymus at different ages may be helpful in planning of the medical and surgical treatment of thymus related problem as well as dealing patients from immunologic aspects Objective: To measure the age related changes in weight of the thymus gland of Bangladeshi people Study design: A descriptive type of study Place and period of study: The study was carried out in the Department of Anatomy, IPGMR Dhaka from October 1996 to March 1997. Materials: 40 (forty) thymuses from Bangladeshi cadaver of either sex were taken for this study. Method: The collected samples were divided into four age groups ranged from still born to sixty years old individuals and comparative studies were done between different age groups. Result: The thymuses increased significantly in weight steadily through the increasing age groups from the still born babies to <16yrs and then declines through the age still higher. Conclusion: In the present study the weight of the thymus increases through the increasing age groups and then declined. Key words: Thymus; Weight DOI: 10.3329/bja.v8i1.6101 Bangladesh Journal of Anatomy January 2010, Vol. 8 No. 1 pp. 10-12

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