scholarly journals Modulation of Autophagy: A Novel “Rejuvenation” Strategy for the Aging Liver

2021 ◽  
Vol 2021 ◽  
pp. 1-30
Author(s):  
Fengming Xu ◽  
Hans-Michael Tautenhahn ◽  
Olaf Dirsch ◽  
Uta Dahmen
Keyword(s):  
Hepatocyte Proliferation ◽  
Detailed Knowledge ◽  
Recycling Process ◽  
Physiological Processes ◽  
Promising Strategy ◽  
Age Related ◽  
Malignant Liver Disease ◽  
The Individual ◽  
Malignant Liver ◽  
And Function

Aging is a natural life process which leads to a gradual decline of essential physiological processes. For the liver, it leads to alterations in histomorphology (steatosis and fibrosis) and function (protein synthesis and energy generation) and affects central hepatocellular processes (autophagy, mitochondrial respiration, and hepatocyte proliferation). These alterations do not only impair the metabolic capacity of the liver but also represent important factors in the pathogenesis of malignant liver disease. Autophagy is a recycling process for eukaryotic cells to degrade dysfunctional intracellular components and to reuse the basic substances. It plays a crucial role in maintaining cell homeostasis and in resisting environmental stress. Emerging evidence shows that modulating autophagy seems to be effective in improving the age-related alterations of the liver. However, autophagy is a double-edged sword for the aged liver. Upregulating autophagy alleviates hepatic steatosis and ROS-induced cellular stress and promotes hepatocyte proliferation but may aggravate hepatic fibrosis. Therefore, a well-balanced autophagy modulation strategy might be suitable to alleviate age-related liver dysfunction. Conclusion. Modulation of autophagy is a promising strategy for “rejuvenation” of the aged liver. Detailed knowledge regarding the most devastating processes in the individual patient is needed to effectively counteract aging of the liver without causing obvious harm.

scholarly journals The Avian Proghrelin System

2010 ◽  
Vol 2010 ◽  
pp. 1-14 ◽  
Author(s):  
Mark P. Richards ◽  
John P. McMurtry
Keyword(s):  
Energy Homeostasis ◽  
Animal Species ◽  
Endocrine System ◽  
Precursor Protein ◽  
Detailed Knowledge ◽  
Physiological Processes ◽  
Tract Function ◽  
Species Comparisons ◽  
The Individual ◽  
And Function

To understand how the proghrelin system functions in regulating growth hormone release and food intake as well as defining its pleiotropic roles in such diverse physiological processes as energy homeostasis, gastrointestinal tract function and reproduction require detailed knowledge of the structure and function of the components that comprise this system. These include the preproghrelin gene that encodes the proghrelin precursor protein from which two peptide hormones, ghrelin and obestatin, are derived and the cognate receptors that bind proghrelin-derived peptides to mediate their physiological actions in different tissues. Also key to the functioning of this system is the posttranslational processing of the proghrelin precursor protein and the individual peptides derived from it. While this system has been intensively studied in a variety of animal species and humans over the last decade, there has been considerably less investigation of the avian proghrelin system which exhibits some unique differences compared to mammals. This review summarizes what is currently known about the proghrelin system in birds and offers new insights into the nature and function of this important endocrine system. Such information facilitates cross-species comparisons and contributes to our understanding of the evolution of the proghrelin system.

The CCL7-CCL2-CCR2 Axis Regulates Age-Related Alterations in ADSCs 

2021 ◽  
Author(s):  
Keya Li ◽  
Guiying Shi ◽  
Xuepei Lei ◽  
Yiying Huang ◽  
Xinyue Li ◽  
...  
Keyword(s):  
Autologous Transplantation ◽  
Hippo Signaling ◽  
Related Disorder ◽  
Promising Strategy ◽  
Age Related ◽  
Minimum Number ◽  
And Function ◽  
The Relationship ◽  
Harmful Effects

Abstract Background and ObjectivesAdipose-tissue derived stem cells (ADSCs) autologous transplantation have been a promising strategy for aging-related disorder. But the relationship between ADSCs senescence and organismal aging were still no consistent conclusions. Toward this end, we analyzed the senescence properties of ADSCs from different age donors to furthermore understand the differences of cells between young and senile donors and verify the influence of organismal aging on the proliferation and function of ADSCs in vitro, providing the theoretical basis for the clinical application of autologous ADSCs transplantation.Methods and ResultsWe detected the characteristics, function, gene expression, apoptosis, cell cycle, SA-β-gal staining, and transcription features of ADSCs from 1-month mice and 20-month mice. ADSCs from old donors had some senescence-associated changes with less ability to proliferation than ADSCs from 1-month mice. Differentiation ability, cell surface markers, and SA-β-Gal staining did not differ across donor age, while cells exhibit a more remarkable age-related changes through continuous passages. According to the results of transcriptome analysis, the CCL7-CCL2-CCR2 axis and Hippo signaling pathway would be considered as its possible mechanisms. ConclusionsOur study reveals that ADSCs from old donors have some age-related alterations. The CCL7-CCL2-CCR2 which lies behind this change would be a potential target for gene therapy to reduce harmful effects of ADSCs from old donors. To make autologous transplantation work better, we would recommend that ADSCs should be cryopreserved in youth with minimum number of passages.

scholarly journals A Review of Dietary (Phyto)Nutrients for Glutathione Support

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2073 ◽  
Author(s):  
Deanna M. Minich ◽  
Benjamin I. Brown
Keyword(s):  
Disease Risk ◽  
Redox Balance ◽  
Nutritional Interventions ◽  
Physiological Processes ◽  
Glutathione Status ◽  
Age Related ◽  
Metabolic Detoxification ◽  
The Individual ◽  
Nutritional Strategies ◽  
Considerable Body

Glutathione is a tripeptide that plays a pivotal role in critical physiological processes resulting in effects relevant to diverse disease pathophysiology such as maintenance of redox balance, reduction of oxidative stress, enhancement of metabolic detoxification, and regulation of immune system function. The diverse roles of glutathione in physiology are relevant to a considerable body of evidence suggesting that glutathione status may be an important biomarker and treatment target in various chronic, age-related diseases. Yet, proper personalized balance in the individual is key as well as a better understanding of antioxidants and redox balance. Optimizing glutathione levels has been proposed as a strategy for health promotion and disease prevention, although clear, causal relationships between glutathione status and disease risk or treatment remain to be clarified. Nonetheless, human clinical research suggests that nutritional interventions, including amino acids, vitamins, minerals, phytochemicals, and foods can have important effects on circulating glutathione which may translate to clinical benefit. Importantly, genetic variation is a modifier of glutathione status and influences response to nutritional factors that impact glutathione levels. This narrative review explores clinical evidence for nutritional strategies that could be used to improve glutathione status.

scholarly journals Nutrition and microRNAs: Novel Insights to Fight Sarcopenia

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 951
Author(s):  
Alessandra Barbiera ◽  
Laura Pelosi ◽  
Gigliola Sica ◽  
Bianca Maria Scicchitano
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Molecular Mechanisms ◽  
Muscle Protein ◽  
Low Grade ◽  
Protein Homeostasis ◽  
Dietary Interventions ◽  
Physiological Processes ◽  
Age Related ◽  
And Function

Sarcopenia is a progressive age-related loss of skeletal muscle mass and strength, which may result in increased physical frailty and a higher risk of adverse events. Low-grade systemic inflammation, loss of muscle protein homeostasis, mitochondrial dysfunction, and reduced number and function of satellite cells seem to be the key points for the induction of muscle wasting, contributing to the pathophysiological mechanisms of sarcopenia. While a range of genetic, hormonal, and environmental factors has been reported to contribute to the onset of sarcopenia, dietary interventions targeting protein or antioxidant intake may have a positive effect in increasing muscle mass and strength, regulating protein homeostasis, oxidative reaction, and cell autophagy, thus providing a cellular lifespan extension. MicroRNAs (miRNAs) are endogenous small non-coding RNAs, which control gene expression in different tissues. In skeletal muscle, a range of miRNAs, named myomiRNAs, are involved in many physiological processes, such as growth, development, and maintenance of muscle mass and function. This review aims to present and to discuss some of the most relevant molecular mechanisms related to the pathophysiological effect of sarcopenia. Besides, we explored the role of nutrition as a possible way to counteract the loss of muscle mass and function associated with ageing, with special attention paid to nutrient-dependent miRNAs regulation. This review will provide important information to better understand sarcopenia and, thus, to facilitate research and therapeutic strategies to counteract the pathophysiological effect of ageing.

scholarly journals Irving S. Wright Award: Cellular recycling in aging and disease: The importance of taking out the trash

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 386-386
Author(s):  
Malene Hansen
Keyword(s):  
Quality Control ◽  
Normal Aging ◽  
Recycling Process ◽  
C Elegans ◽  
Control Processes ◽  
Age Related ◽  
Round Worm ◽  
And Function

Abstract Aging is greatly influenced by quality-control processes that keep the materials inside our cells in proper shape and function. One of these processes is called autophagy, which means "self-eating". This cellular recycling process can digest damaged components to provide new and better parts for the cell. Autophagy plays important roles in many age-related diseases and has been directly linked to aging. In our laboratory, we use the microscopic soil-dwelling round worm C. elegans to understand how autophagy is linked to aging and disease. In this Wright Award seminar, I will discuss our progress on understanding how autophagy is regulated during normal aging and how it may promote a long and healthy lifespan.

scholarly journals ABC Transporters in T Cell-Mediated Physiological and Pathological Immune Responses

2021 ◽  
Vol 22 (17) ◽  
pp. 9186
Author(s):  
Christoph Thurm ◽  
Burkhart Schraven ◽  
Sascha Kahlfuss
Keyword(s):  
T Cells ◽  
T Cell ◽  
Abc Transporters ◽  
Current Knowledge ◽  
Cell Types ◽  
Cell Populations ◽  
Physiological Processes ◽  
The Individual ◽  
Dependent Transport ◽  
And Function

ATP-binding cassette (ABC) transporters represent a heterogeneous group of ATP-dependent transport proteins, which facilitate the import and/or export of various substrates, including lipids, sugars, amino acids and peptides, ions, and drugs. ABC transporters are involved in a variety of physiological processes in different human tissues. More recent studies have demonstrated that ABC transporters also regulate the development and function of different T cell populations, such as thymocytes, Natural Killer T cells, CD8+ T cells, and CD4+ T helper cells, including regulatory T cells. Here, we review the current knowledge on ABC transporters in these T cell populations by summarizing how ABC transporters regulate the function of the individual cell types and how this affects the immunity to viruses and tumors, and the course of autoimmune diseases. Furthermore, we provide a perspective on how a better understanding of the function of ABC transporters in T cells might provide promising novel avenues for the therapy of autoimmunity and to improve immunity to infection and cancer.

scholarly journals H3K4me3 enrichment defines neuronal age, while a youthful H3K27ac signature is recapitulated in aged neurons

2021 ◽  
Author(s):  
Katherine A Giles ◽  
Andrew J Phipps ◽  
Jake M Cashion ◽  
Shannon N Huskins ◽  
Timothy R Mercer ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Old Age ◽  
Epigenetic Alterations ◽  
Neuron Morphology ◽  
Age Related ◽  
Genome Wide ◽  
The Individual ◽  
And Function ◽  
Age Related Cognitive Decline ◽  
Neuronal Output

Neurons live for the lifespan of the individual and underlie our ability for lifelong learning and memory. However, aging alters neuron morphology and function resulting in age-related cognitive decline. It is well established that epigenetic alterations are essential for learning and memory, yet few neuron-specific genome-wide epigenetic maps exist into old age. Comprehensive mapping of H3K4me3 and H3K27ac in mouse neurons across lifespan revealed plastic H3K4me3 marking that differentiates neuronal age linked to known characteristics of cellular and neuronal aging. We determined that neurons in old age recapitulate the H3K27ac enrichment at promoters, enhancers and super enhancers from young adult neurons, likely representing a re-activation of pathways to maintain neuronal output. Finally, this study identified new characteristics of neuronal aging, including altered rDNA regulation and epigenetic regulatory mechanisms. Collectively, these findings indicate a key role for epigenetic regulation in neurons, that is inextricably linked with aging.

Narrow is the Gate to Utopia

Moreana ◽  
2012 ◽  
Vol 49 (Number 187- (1-2) ◽  
pp. 207-226
Author(s):  
Marie-Claire Phélippeau
Keyword(s):  
Social Construction ◽  
Free Will ◽  
Religious Toleration ◽  
Individual Liberty ◽  
The Reformation ◽  
The Individual ◽  
And Function

This study examines the notions of pleasure, individual liberty and consensus in Thomas More’s Utopia. The paradox inherent in Utopia, written before the Reformation, is especially visible in the affirmation of religious toleration coexisting with the need for a strict supervision of the citizens. The dream of an ideal republic is based on a Pauline vision of man which defines the individual mainly as a sinner. Consequently, it is the duty of the republic’s rulers to guide the citizens and establish a consensus. This study tries to determine the part left to the individual’s free will and examines the nature and function of the structures that are supposed to ensure the happiness of each one and of the whole community. The notion of moral hierarchy is asserted as the linchpin of the Utopian social construction.

Matrix Metalloproteinases in Invertebrates

2020 ◽  
Vol 27 (11) ◽  
pp. 1068-1081
Author(s):  
Xi Liu ◽  
Dongwu Liu ◽  
Yangyang Shen ◽  
Mujie Huang ◽  
Lili Gao ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Immune Responses ◽  
Theoretical Basis ◽  
Regulatory Mechanism ◽  
Structure And Function ◽  
Catalytic Domains ◽  
Physiological Processes ◽  
Disease Occurrence ◽  
Complex Functions ◽  
And Function

Matrix Metalloproteinases (MMPs) belong to a family of metal-dependent endopeptidases which contain a series of conserved pro-peptide domains and catalytic domains. MMPs have been widely found in plants, animals, and microorganisms. MMPs are involved in regulating numerous physiological processes, pathological processes, and immune responses. In addition, MMPs play a key role in disease occurrence, including tumors, cardiovascular diseases, and other diseases. Compared with invertebrate MMPs, vertebrate MMPs have diverse subtypes and complex functions. Therefore, it is difficult to study the function of MMPs in vertebrates. However, it is relatively easy to study invertebrate MMPs because there are fewer subtypes of MMPs in invertebrates. In the present review, the structure and function of MMPs in invertebrates were summarized, which will provide a theoretical basis for investigating the regulatory mechanism of MMPs in invertebrates.

scholarly journals Adolescent and adult laryngotracheal stenosis: a review

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Gerhard Johan Klopper ◽  
Oladele Vincent Adeniyi ◽  
Kate Stephenson
Keyword(s):  
Intensive Care ◽  
Past Century ◽  
Main Body ◽  
Laryngotracheal Stenosis ◽  
Airway Protection ◽  
Interventional Pulmonology ◽  
The Past ◽  
Airway Emergency ◽  
The Individual ◽  
And Function

Abstract Background The larynx has multiple composite functions which include phonation, airway protection, and sensory control of respiration. Stenosis of the larynx and trachea were first recorded by O’Dwyer in 1885 and by Colles in 1886, respectively. Initially, the aetiology of laryngotracheal stenosis was predominantly infective. Currently, the leading cause is iatrogenic injury to the laryngotracheal complex secondary to prolonged ventilation in an intensive care unit. Main body Laryngotracheal stenosis is a complex and diverse disease. It poses a major challenge to the surgeon and can present as an airway emergency. Management typically demands the combined involvement of various disciplines including otorhinolaryngology, cardiothoracic surgery, anaesthesiology, interventional pulmonology, and radiology. Both the disease and its management can impact upon respiration, voice, and swallowing. The incidence of iatrogenic laryngotracheal stenosis has reflected the evolution of airway and intensive care whilst airway surgery has advanced concurrently over the past century. Correction of laryngotracheal stenosis requires expansion of the airway lumen; this is achieved by either endoscopic or open surgery. We review the relevant basic science, aetiopathogenesis, diagnosis, management, and treatment outcomes of LTS. Conclusion The choice of surgical procedure in the management of laryngotracheal stenosis is often dictated by the individual anatomy and function of the larynx and trachea, together with patient factors and available facilities. Regardless of how the surgeon chooses to approach these lesions, prevention of iatrogenic laryngotracheal damage remains of primary importance.

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