scholarly journals dCubilin/dAMN- mediated protein reabsorption in Drosophila nephrocytes modulates longevity

2021 ◽  
Author(s):  
Xiaoming Feng ◽  
Xizhen Hong ◽  
Qiuxia Fan ◽  
Liting Chen ◽  
Jing Li ◽  
...  
Keyword(s):  
Aging Process ◽  
Whole Body ◽  
Genetic Enhancement ◽  
Neuronal Tissue ◽  
Age Related ◽  
Muscle Tissues ◽  
Protein Reabsorption ◽  
Cellular Pathways ◽  
Different Tissues

Aging is a multi-faceted process regulated by multiple cellular pathways, including the proteostasis network. Pharmacological or genetic enhancement of the intracellular proteostasis network extends lifespan and prevents age-related diseases. However, how proteostasis is regulated in different tissues throughout the aging process remains unclear. Here, we show that Drosophila homologs for Cubulin/Amnionless (dCubilin/dAMN)-mediated protein reabsorption from hemolymph (fly equivalent of blood) by nephrocytes modulates longevity through regulating proteostasis in muscle and brain tissues in Drosophila. We find that overexpression of dAMN receptor in nephrocytes extends lifespan, whereas nephrocyte-specific dCubilin or dAMN RNAi knockdown results in a protein reabsorption defect and shortens lifespan in flies. And we show that dCubilin/dAMN-mediated protein reabsorption in nephrocytes regulates proteostasis in hemolymph and improves healthspan. In addition, we show that enhanced dCubilin/dAMN-mediated protein reabsorption in nephrocytes slows down the aging process in muscle and brain by maintaining the proteostasis network in these tissues. Furthermore, our study shows that dCubilin/dAMN -mediated protein reabsorption in nephrocytes affects proteasome activity in the whole body and muscle tissues. Altogether, our work has revealed an inter-organ communication network across nephrocytes and muscle/neuronal tissue which is essential to maintain proteostasis and to delay senescence in these organs. The findings have provided insights into the role of renal protein reabsorption in the aging process via this tele-proteostasis network.

Oxidative stress and aging: Is methylglyoxal the hidden enemy?This review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.

2010 ◽  
Vol 88 (3) ◽  
pp. 273-284 ◽  
Author(s):  
Kaushik M. Desai ◽  
Tuanjie Chang ◽  
Hui Wang ◽  
Ali Banigesh ◽  
Arti Dhar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Aging Process ◽  
Cellular Tissue ◽  
Cardiovascular Complications ◽  
Whole Body ◽  
Age Related ◽  
Transport Chain ◽  
Glycation End Products ◽  
Health And Disease

Aging is a multifactorial process that involves changes at the cellular, tissue, organ and the whole body levels resulting in decreased functioning, development of diseases, and ultimately death. Oxidative stress is believed to be a very important factor in causing aging and age-related diseases. Oxidative stress is caused by an imbalance between oxidants such as reactive oxygen species (ROS) and antioxidants. ROS are produced from the mitochondrial electron transport chain and many oxidative reactions. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite formed during glucose, protein and fatty acid metabolism. MG levels are elevated in hyperglycemia and other conditions. An excess of MG formation can increase ROS production and cause oxidative stress. MG reacts with proteins, DNA and other biomolecules, and is a major precursor of advanced glycation end products (AGEs). AGEs are also associated with the aging process and age-related diseases such as cardiovascular complications of diabetes, neurodegenerative diseases and connective tissue disorders. AGEs also increase oxidative stress. In this review we discuss the potential role of MG in the aging process through increasing oxidative stress besides causing AGEs formation. Specific and effective scavengers and crosslink breakers of MG and AGEs are being developed and can become potential treatments to slow the aging process and prevent many diseases.

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 Role of transposable elements in age-related genomic instability

1997 ◽  
Vol 69 (3) ◽  
pp. 183-195 ◽  
Author(s):  
A. G. NIKITIN ◽  
R. J. SHMOOKLER REIS
Keyword(s):  
Transposable Elements ◽  
Genomic Instability ◽  
Genetic Instability ◽  
Aging Process ◽  
Biological Systems ◽  
Age Related ◽  
Eukaryotic Organisms ◽  
Initiating Factors

Genetic instability is associated with aging in many species. One of the initiating factors for genetic instability is the movement of transposable elements (TEs), which occur in all prokaryotic and eukaryotic organisms. The hypothesis that TEs could be involved in the aging process is discussed and the correlation between aging and activity of TEs is analysed in a variety of biological systems.

scholarly journals Loxl2 is a mediator of cardiac aging in Drosophila melanogaster; genetically examining the role of aging clock genes

2021 ◽  
Author(s):  
Mark J Bouska ◽  
Hua Bai
Keyword(s):  
Drosophila Melanogaster ◽  
Clock Genes ◽  
Turning Points ◽  
Whole Body ◽  
Specific Gene ◽  
Age Related ◽  
Human Orthologs ◽  
Age Range ◽  
Transcriptional Target

Abstract Transcriptomic, proteomic, and methylation aging clocks demonstrate that aging has a predictable preset program, while Transcriptome Trajectory Turning Points indicate that the 20 to 40 age range in humans is the likely stage at which the progressive loss of homeostatic control, and in turn aging, begins to have detrimental effects. Turning points in this age range overlapping with human aging clock genes revealed five candidates that we hypothesized could play a role in aging or age-related physiological decline. To examine these gene’s effects on lifespan and health-span, we utilized whole body and heart specific gene knockdown of human orthologs in Drosophila melanogaster. Whole body Loxl2, fz3, and Glo1 RNAi positively affected lifespan as did heart-specific Loxl2 knockdown. Loxl2 inhibition concurrently reduced age-related cardiac arrythmia and collagen (Pericardin) fiber width. Loxl2 binds several transcription factors in humans and RT-qPCR confirmed that a conserved transcriptional target CDH1 (Drosophila CadN2), has expression levels which correlate with Loxl2 reduction in Drosophila. These results point to conserved pathways and multiple mechanisms by which inhibition of Loxl2 can be beneficial to heart health and organismal aging.

scholarly journals Bioactive Nutrients and Nutrigenomics in Age-Related Diseases

2016 ◽  
Author(s):  
Tania Rescigno ◽  
Mario F. Tecce ◽  
Anna Capasso
Keyword(s):  
Oxidative Stress ◽  
Immune System ◽  
Aging Process ◽  
Bioactive Molecules ◽  
Low Grade ◽  
Molecular Processes ◽  
Ample Evidence ◽  
Inflammatory Status ◽  
Age Related

The increase in the average lifespan and the consequent proportional growth of the elderly segment of society has furthered the interest in studying ageing processes. Ageing may be considered a multifactorial process derived from the interaction between genetic and environmental factors including lifestyle. There is ample evidence in many species that the maximum age attainable (maximum lifespan potential, MLSP) is genetically determined and several mitochondrial DNA polymorphisms are associated with longevity. Many studies have shown that most of the phenotypic characteristics observed in the aging process are the result of the occurrence, with age, of a low grade chronic pro-inflammatory status called "inflammaging", partially under genetic control. The term indicate that aging is accompanied by a low degree of chronic inflammatory, an up-regulation of inflammatory response and that inflammatory changes are common to many age-related diseases. Therefore, the theory of oxidation-inflammation was proposed as the main cause of aging. Accordingly, the chronic oxidative stress, that appears with age, affects all cells and especially those of the regulatory systems, such as the nervous, endocrine, and immune systems and the communication between them. This prevents an adequate homeostasis and, therefore, the preservation of health. It was also proposed that the immune system plays a key role in the aging process, specifically in the rate of aging, since there is a relationship between the redox state and functional capacity of immune cells and longevity of individuals. Moreover, the role of the immune system in senescence could be of universal application. A confirmation of the central role of the immune system in oxi-inflamm-aging is that the administrationintake? of adequate amounts of antioxidants in the diet improves immune function, decreases their oxidative stress, and consequently increases longevity. The promotion of healthy lifestyles is one of the major goals of governments and international agencies all over the world. Human molecular processes are influenced by both physiological pathways and exogenous factors which include, for instance, those originating from diet. Dietary intake has substantive effects on molecular processes of metabolic health. Nutrients can directly regulate physiological changes in human body. In fact, in addition to have an energetic and structural value, nutritional intake provides bioactive molecules which are selectively able to modulate specific metabolic pathways, noticeably affecting cardiovascular and neoplastic diseases development or progress. Numerous bioactive nutrients are being progressively identified and their chemopreventive effects are being described at clinical and molecular mechanism levels. Systematic analyses comprise all “omics” technologies (such as transcriptomics, proteomics and metabolomics) and the goal is to investigate bioactive molecules effects derived from the diet. Nutrigenomic knowledge on physiologic status and disease risk will provide both developments of better diagnostic procedures and of new therapeutic strategies specifically targeted on nutritionally relevant processes. The present review was aimed to understand the molecular mechanisms underlying beneficial effects of bioactive nutrients and nutrigenomics on age-related diseases.

scholarly journals Comprehensive longitudinal study of epigenetic mutations in aging

2019 ◽  
Author(s):  
Yunzhang Wang ◽  
Robert Karlsson ◽  
Juulia Jylhävä ◽  
Åsa K. Hedman ◽  
Catarina Almqvist ◽  
...  
Keyword(s):  
Cancer Diagnosis ◽  
Genetic Background ◽  
Aging Process ◽  
Genetic Factors ◽  
Aberrant Methylation ◽  
Contributing Factors ◽  
Cross Sectional ◽  
Age Related ◽  
Comprehensive Study

AbstractBackgroundThe role of DNA methylation in aging has been widely studied. However, epigenetic mutations, here defined as aberrant methylation levels compared to the distribution in a population, are less understood. Hence, we investigated longitudinal accumulation of epigenetic mutations, using 994 blood samples collected at up to five time points from 375 individuals in old ages.ResultsWe verified earlier cross-sectional evidence on the increase of epigenetic mutations with age, and identified important contributing factors including sex, CD19+ B cells, genetic background, cancer diagnosis and technical artifacts. We further classified epigenetic mutations into High/Low Methylation Outliers (HMO/LMO) according to their changes in methylation, and specifically studied methylation sites (CpGs) that were prone to mutate (frequently mutated CpGs). We validated four epigenetically mutated CpGs using pyrosequencing in 93 samples. Furthermore, by using twins, we concluded that the age-related accumulation of epigenetic mutations was not related to genetic factors, hence driven by stochastic or environmental effects.ConclusionsHere we conducted a comprehensive study of epigenetic mutation and highlighted its important role in aging process and cancer development.

scholarly journals Epigenetics of aging and disease: a brief overview

2019 ◽  
Author(s):  
Christina Pagiatakis ◽  
Elettra Musolino ◽  
Rosalba Gornati ◽  
Giovanni Bernardini ◽  
Roberto Papait
Keyword(s):  
Gene Expression ◽  
Neurodegenerative Disorders ◽  
Potential Role ◽  
Molecular Level ◽  
Physiological Function ◽  
Regulate Gene Expression ◽  
Age Related ◽  
Genetic And Environmental Factors ◽  
Different Tissues

AbstractAging is an important risk factor for several human diseases such as cancer, cardiovascular disease and neurodegenerative disorders, resulting from a combination of genetic and environmental factors (e.g., diet, smoking, obesity and stress), which, at molecular level, cause changes in gene expression underlying the decline of physiological function. Epigenetics, which include mechanisms regulating gene expression independently of changes to DNA sequence, regulate gene expression by modulating the structure of chromatin or by regulating the binding of transcriptional machinery to DNA. Several studies showed that an impairment of epigenetic mechanisms promotes alteration of gene expression underlying several aging-related diseases. Alteration of these mechanisms is also linked with changes of gene expression that occurs during aging processes of different tissues. In this review, we will outline the potential role of epigenetics in the onset of two age-related pathologies, cancer and cardiovascular diseases.

scholarly journals Comprehensive longitudinal study of epigenetic mutations in aging

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Yunzhang Wang ◽  
Robert Karlsson ◽  
Juulia Jylhävä ◽  
Åsa K. Hedman ◽  
Catarina Almqvist ◽  
...  
Keyword(s):  
Cancer Diagnosis ◽  
Genetic Background ◽  
Aging Process ◽  
Genetic Factors ◽  
Aberrant Methylation ◽  
Contributing Factors ◽  
Cross Sectional ◽  
Age Related ◽  
Comprehensive Study

Abstract Background The role of DNA methylation in aging has been widely studied. However, epigenetic mutations, here defined as aberrant methylation levels compared to the distribution in a population, are less understood. Hence, we investigated longitudinal accumulation of epigenetic mutations, using 994 blood samples collected at up to five time points from 375 individuals in old ages. Results We verified earlier cross-sectional evidence on the increase of epigenetic mutations with age, and identified important contributing factors including sex, CD19+ B cells, genetic background, cancer diagnosis, and technical artifacts. We further classified epigenetic mutations into High/Low Methylation Outliers (HMO/LMO) according to their changes in methylation, and specifically studied methylation sites (CpGs) that were prone to mutate (frequently mutated CpGs). We validated four epigenetically mutated CpGs using pyrosequencing in 93 samples. Furthermore, by using twins, we concluded that the age-related accumulation of epigenetic mutations was not related to genetic factors, hence driven by stochastic or environmental effects. Conclusions Here we conducted a comprehensive study of epigenetic mutation and highlighted its important role in aging process and cancer development.

scholarly journals Synuclein Deficiency Results in Age-Related Respiratory and Cardiovascular Dysfunctions in Mice

2020 ◽  
Vol 10 (9) ◽  
pp. 583
Author(s):  
Patrick S. Hosford ◽  
Natalia Ninkina ◽  
Vladimir L. Buchman ◽  
Jeffrey C. Smith ◽  
Nephtali Marina ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Physiological Role ◽  
Normal Function ◽  
Whole Body ◽  
Cardiovascular Reflexes ◽  
Long Term Effects ◽  
Gene Encoding ◽  
Age Related

Synuclein (α, β, and γ) proteins are highly expressed in presynaptic terminals, and significant data exist supporting their role in regulating neurotransmitter release. Targeting the gene encoding α-synuclein is the basis of many animal models of Parkinson’s disease (PD). However, the physiological role of this family of proteins in not well understood and could be especially relevant as interfering with accumulation of α-synuclein level has therapeutic potential in limiting PD progression. The long-term effects of their removal are unknown and given the complex pathophysiology of PD, could exacerbate other clinical features of the disease, for example dysautonomia. In the present study, we sought to characterize the autonomic phenotypes of mice lacking all synucleins (α, β, and γ; αβγ−/−) in order to better understand the role of synuclein-family proteins in autonomic function. We probed respiratory and cardiovascular reflexes in conscious and anesthetized, young (4 months) and aged (18–20 months) αβγ−/− male mice. Aged mice displayed impaired respiratory responses to both hypoxia and hypercapnia when breathing activities were recorded in conscious animals using whole-body plethysmography. These animals were also found to be hypertensive from conscious blood pressure recordings, to have reduced pressor baroreflex gain under anesthesia, and showed reduced termination of both pressor and depressor reflexes. The present data demonstrate the importance of synuclein in the normal function of respiratory and cardiovascular reflexes during aging.

scholarly journals DNA damage responses and p53 in the aging process

Blood ◽  
2018 ◽  
Vol 131 (5) ◽  
pp. 488-495 ◽  
Author(s):  
Hui-Ling Ou ◽  
Björn Schumacher
Keyword(s):  
Dna Damage ◽  
Aging Process ◽  
Tumor Development ◽  
Cancer Development ◽  
Adaptive Responses ◽  
Genome Maintenance ◽  
Age Related ◽  
Progeroid Syndromes ◽  
Process Studies

Abstract The genome is constantly attacked by genotoxic insults. DNA damage has long been established as a cause of cancer development through its mutagenic consequences. Conversely, radiation therapy and chemotherapy induce DNA damage to drive cells into apoptosis or senescence as outcomes of the DNA damage response (DDR). More recently, DNA damage has been recognized as a causal factor for the aging process. The role of DNA damage in aging and age-related diseases is illustrated by numerous congenital progeroid syndromes that are caused by mutations in genome maintenance pathways. During the past 2 decades, understanding how DDR drives cancer development and contributes to the aging process has progressed rapidly. It turns out that the DDR factor p53 takes center stage during tumor development and also plays an important role in the aging process. Studies in metazoan models ranging from Caenorhabditis elegans to mammals have revealed cell-autonomous and systemic DDR mechanisms that orchestrate adaptive responses that augment maintenance of the aging organism amid gradually accumulating DNA damage.

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