Key miRNAs in Modulating Aging and Longevity: A Focus on Signaling Pathways and Cellular Targets

2021 ◽  
Vol 14 ◽  
Author(s):  
Aliabbas Zia ◽  
Tahereh Farkhondeh ◽  
Faezeh Sahebdel ◽  
Ali Mohammad Pourbagher-Shahri ◽  
Saeed Samarghandian
Keyword(s):  
Cellular Senescence ◽  
Cell Biology ◽  
Specific Binding ◽  
Model Organisms ◽  
Specific Expression ◽  
Cellular Targets ◽  
Age Related ◽  
Muscle Tissues ◽  
Mammalian Tissues ◽  
Tissue Aging

: Aging is a multifactorial procedure accompanied by gradual deterioration of most biological procedures of cells. MicroRNAs (miRNAs) are a class of short non-coding RNAs that post-transcriptionally regulate the expression of mRNAs through sequence-specific binding, and contributing to many crucial aspects of cell biology. Several miRNAs are expressed differently in various organisms through aging. The function of miRNAs in modulating aging procedures has been disclosed recently with the detection of miRNAs that modulate longevity in the invertebrate model organisms, through the IIS pathway. In these model organisms, several miRNAs have been detected to both negatively and positively regulate lifespan via commonly aging pathways. miRNAs modulate age-related procedures and disorders in different mammalian tissues by measuring their tissue-specific expression in older and younger counterparts, including heart, skin, bone, brain, and muscle tissues. Moreover, several miRNAs have been contributed to modulating senescence in different human cells, and the roles of these miRNAs in modulating cellular senescence have allowed illustrating some mechanisms of aging. The review discusses the available data on miRNAs through the aging process and we highlight the roles of miRNAs as aging biomarkers and regulators of longevity in cellular senescence, tissue aging, and organism lifespan.

scholarly journals Cellular Senescence and Mammalian Healthspan

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 742-742
Author(s):  
Judith Campisi
Keyword(s):  
Growth Factors ◽  
Cell Fate ◽  
Cellular Senescence ◽  
Complex Cell ◽  
Transgenic Mouse Models ◽  
Bioactive Lipids ◽  
Age Related ◽  
Mammalian Tissues ◽  
Secretory Phenotype ◽  
Near Future

Abstract Cellular senescence is a complex cell fate, often induced by stress or damage, that can be beneficial or deleterious, depending on the physiological context and age of the organism. A prominent feature of senescent cells is a multi-faceted senescence-associated secretory phenotype (SASP), which includes growth factors, cytokine and chemokines, growth factors, proteases, bioactive lipids and metabolites. Senescent cells increase with age in most, if not all, mammalian tissues. Through the use of transgenic mouse models, senescent cells are now known to causally drive numerous age-related pathologies, largely through the SASP. Eliminating senescent cells, genetically or through the use of senolytic/senomorphic agents, can improve the health span, at least in mice, and hold promise for extension to humans in the near future.

scholarly journals An economical and highly adaptable optogenetics system for individual and population-level manipulation of Caenorhabditis elegans

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
M. Koopman ◽  
L. Janssen ◽  
E. A. A. Nollen
Keyword(s):  
Caenorhabditis Elegans ◽  
Light Stimulus ◽  
Cholinergic Neurons ◽  
Model Organisms ◽  
Parameter Study ◽  
Multiple Model ◽  
Excitable Cells ◽  
Specific Expression ◽  
C Elegans ◽  
Age Related

Abstract Background Optogenetics allows the experimental manipulation of excitable cells by a light stimulus without the need for technically challenging and invasive procedures. The high degree of spatial, temporal, and intensity control that can be achieved with a light stimulus, combined with cell type-specific expression of light-sensitive ion channels, enables highly specific and precise stimulation of excitable cells. Optogenetic tools have therefore revolutionized the study of neuronal circuits in a number of models, including Caenorhabditis elegans. Despite the existence of several optogenetic systems that allow spatial and temporal photoactivation of light-sensitive actuators in C. elegans, their high costs and low flexibility have limited wide access to optogenetics. Here, we developed an inexpensive, easy-to-build, modular, and adjustable optogenetics device for use on different microscopes and worm trackers, which we called the OptoArm. Results The OptoArm allows for single- and multiple-worm illumination and is adaptable in terms of light intensity, lighting profiles, and light color. We demonstrate OptoArm’s power in a population-based multi-parameter study on the contributions of motor circuit cells to age-related motility decline. We found that individual components of the neuromuscular system display different rates of age-dependent deterioration. The functional decline of cholinergic neurons mirrors motor decline, while GABAergic neurons and muscle cells are relatively age-resilient, suggesting that rate-limiting cells exist and determine neuronal circuit ageing. Conclusion We have assembled an economical, reliable, and highly adaptable optogenetics system which can be deployed to address diverse biological questions. We provide a detailed description of the construction as well as technical and biological validation of our set-up. Importantly, use of the OptoArm is not limited to C. elegans and may benefit studies in multiple model organisms, making optogenetics more accessible to the broader research community.

scholarly journals Insights from In Vivo Studies of Cellular Senescence

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 954
Author(s):  
Luis I. Prieto ◽  
Sara I. Graves ◽  
Darren J. Baker
Keyword(s):  
Cellular Senescence ◽  
Cell Biology ◽  
Senescent Cell ◽  
In Vivo Studies ◽  
Cycle Arrest ◽  
Mammalian Cell Lines ◽  
Age Related ◽  
Cell Accumulation ◽  
Secretory Phenotype

Cellular senescence is the dynamic process of durable cell-cycle arrest. Senescent cells remain metabolically active and often acquire a distinctive bioactive secretory phenotype. Much of our molecular understanding in senescent cell biology comes from studies using mammalian cell lines exposed to stress or extended culture periods. While less well understood mechanistically, senescence in vivo is becoming appreciated for its numerous biological implications, both in the context of beneficial processes, such as development, tumor suppression, and wound healing, and in detrimental conditions, where senescent cell accumulation has been shown to contribute to aging and age-related diseases. Importantly, clearance of senescent cells, through either genetic or pharmacological means, has been shown to not only extend the healthspan of prematurely and naturally aged mice but also attenuate pathology in mouse models of chronic disease. These observations have prompted an investigation of how and why senescent cells accumulate with aging and have renewed exploration into the characteristics of cellular senescence in vivo. Here, we highlight our molecular understanding of the dynamics that lead to a cellular arrest and how various effectors may explain the consequences of senescence in tissues. Lastly, we discuss how exploitation of strategies to eliminate senescent cells or their effects may have clinical utility.

scholarly journals The Role of Curcumin in the Modulation of Ageing

2019 ◽  
Vol 20 (5) ◽  
pp. 1239 ◽  
Author(s):  
Anna Bielak-Zmijewska ◽  
Wioleta Grabowska ◽  
Agata Ciolko ◽  
Agnieszka Bojko ◽  
Grażyna Mosieniak ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Natural Products ◽  
Cellular Senescence ◽  
Current Knowledge ◽  
Model Organisms ◽  
Age Related ◽  
Daily Diet

It is believed that postponing ageing is more effective and less expensive than the treatment of particular age-related diseases. Compounds which could delay symptoms of ageing, especially natural products present in a daily diet, are intensively studied. One of them is curcumin. It causes the elongation of the lifespan of model organisms, alleviates ageing symptoms and postpones the progression of age-related diseases in which cellular senescence is directly involved. It has been demonstrated that the elimination of senescent cells significantly improves the quality of life of mice. There is a continuous search for compounds, named senolytic drugs, that selectively eliminate senescent cells from organisms. In this paper, we endeavor to review the current knowledge about the anti-ageing role of curcumin and discuss its senolytic potential.

scholarly journals Publisher Correction: Genetic tool development in marine protists: emerging model organisms for experimental cell biology

2020 ◽  
Vol 17 (5) ◽  
pp. 551-551
Author(s):  
Drahomíra Faktorová ◽  
R. Ellen R. Nisbet ◽  
José A. Fernández Robledo ◽  
Elena Casacuberta ◽  
Lisa Sudek ◽  
...  
Keyword(s):  
Cell Biology ◽  
Model Organisms ◽  
Tool Development ◽  
Experimental Cell ◽  
Genetic Tool ◽  
Marine Protists

scholarly journals Cellular Senescence in Lung Fibrosis

2021 ◽  
Vol 22 (13) ◽  
pp. 7012
Author(s):  
Fernanda Hernandez-Gonzalez ◽  
Rosa Faner ◽  
Mauricio Rojas ◽  
Alvar Agustí ◽  
Manuel Serrano ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cellular Senescence ◽  
Lung Fibrosis ◽  
Lung Diseases ◽  
Physiological Mechanism ◽  
Lung Parenchyma ◽  
Scar Tissue ◽  
Interstitial Lung Diseases ◽  
Cellular Damage ◽  
Age Related

Fibrosing interstitial lung diseases (ILDs) are chronic and ultimately fatal age-related lung diseases characterized by the progressive and irreversible accumulation of scar tissue in the lung parenchyma. Over the past years, significant progress has been made in our incomplete understanding of the pathobiology underlying fibrosing ILDs, in particular in relation to diverse age-related processes and cell perturbations that seem to lead to maladaptation to stress and susceptibility to lung fibrosis. Growing evidence suggests that a specific biological phenomenon known as cellular senescence plays an important role in the initiation and progression of pulmonary fibrosis. Cellular senescence is defined as a cell fate decision caused by the accumulation of unrepairable cellular damage and is characterized by an abundant pro-inflammatory and pro-fibrotic secretome. The senescence response has been widely recognized as a beneficial physiological mechanism during development and in tumour suppression. However, recent evidence strengthens the idea that it also drives degenerative processes such as lung fibrosis, most likely by promoting molecular and cellular changes in chronic fibrosing processes. Here, we review how cellular senescence may contribute to lung fibrosis pathobiology, and we highlight current and emerging therapeutic approaches to treat fibrosing ILDs by targeting cellular senescence.

scholarly journals Molecular and phenotypic analysis of rodent models reveals conserved and species-specific modulators of human sarcopenia

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Anastasiya Börsch ◽  
Daniel J. Ham ◽  
Nitish Mittal ◽  
Lionel A. Tintignac ◽  
Eugenia Migliavacca ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Inflammatory Responses ◽  
Molecular Data ◽  
Model Organisms ◽  
Sequencing Data ◽  
Phenotypic Analysis ◽  
Age Related ◽  
Analogous Data ◽  
Species Specific ◽  
And Function

AbstractSarcopenia, the age-related loss of skeletal muscle mass and function, affects 5–13% of individuals aged over 60 years. While rodents are widely-used model organisms, which aspects of sarcopenia are recapitulated in different animal models is unknown. Here we generated a time series of phenotypic measurements and RNA sequencing data in mouse gastrocnemius muscle and analyzed them alongside analogous data from rats and humans. We found that rodents recapitulate mitochondrial changes observed in human sarcopenia, while inflammatory responses are conserved at pathway but not gene level. Perturbations in the extracellular matrix are shared by rats, while mice recapitulate changes in RNA processing and autophagy. We inferred transcription regulators of early and late transcriptome changes, which could be targeted therapeutically. Our study demonstrates that phenotypic measurements, such as muscle mass, are better indicators of muscle health than chronological age and should be considered when analyzing aging-related molecular data.

scholarly journals Dendranthema zawadskii var. lucidum (Nakai) J.H. Park Extract Inhibits Cellular Senescence in Human Dermal Fibroblasts and Aging-Related Inflammation in Rats

Processes ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 801
Author(s):  
Jehun Choi ◽  
Gwi-Yeong Jang ◽  
Jeonghoon Lee ◽  
Hae-Young Chung ◽  
Hyung-Jun Noh ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Cell Cycle Progression ◽  
Inflammatory Responses ◽  
Dermal Fibroblast ◽  
Dermal Fibroblasts ◽  
Dependent Manner ◽  
Aged Rats ◽  
Age Related ◽  
Dendranthema Zawadskii ◽  
Beta Galactosidase

Senescence is the phenomenon by which physiological functions of organisms degenerate with time. Cellular senescence is marked by an inhibition of cell cycle progression. Beta-galactosidase accumulates in the lysosomes of aged cells. In this study, human dermal fibroblast cells (HDFs) were treated with 0.5 μM doxorubicin for 4 h to induce cellular senescence. Senescence-associated beta-galactosidase (SA-β-gal) activity was then measured 72 h after treatment with aerial parts of Dendranthema zawadskii var. lucidum (Nakai) J.H. Park (DZ) extract. Treatment with DZ extract significantly decreased SA-β-gal activity in a dose-dependent manner in HDFs. Additionally, DZ extract treatment reduced age-related oxidative stress and inflammation in the aortas of aged rats. The reactive oxygen species (ROS) levels in aortas of aged control rats were higher than those in young rats. However, DZ extract-fed aged rats showed significantly lower ROS levels than the aged control rats. When the aged rats were treated with DZ extract at either 0.2 or 1.0 mg∙kg−1∙day−1, NF-κB levels in aorta tissue decreased significantly compared to those in aorta tissue of the aged control rats without DZ treatment. In addition, DZ extract-fed aged rat aortas showed significant reductions in expression of iNOS and COX-2 induced by NF-κB translocation. Therefore, these results suggest that DZ effectively inhibited senescence-related NF-κB activation and inflammation. DZ extract may have a role in the prevention of the vascular inflammatory responses that occur during vascular aging.

scholarly journals The ATP Synthase Deficiency in Human Diseases

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 325
Author(s):  
Chiara Galber ◽  
Stefania Carissimi ◽  
Alessandra Baracca ◽  
Valentina Giorgio
Keyword(s):  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Mitochondrial Protein ◽  
High Energy ◽  
Neurocognitive Disorders ◽  
Human Diseases ◽  
Age Related ◽  
Muscle Tissues ◽  
Mitochondrial Atp Synthase ◽  
Genes Encoding

Human diseases range from gene-associated to gene-non-associated disorders, including age-related diseases, neurodegenerative, neuromuscular, cardiovascular, diabetic diseases, neurocognitive disorders and cancer. Mitochondria participate to the cascades of pathogenic events leading to the onset and progression of these diseases independently of their association to mutations of genes encoding mitochondrial protein. Under physiological conditions, the mitochondrial ATP synthase provides the most energy of the cell via the oxidative phosphorylation. Alterations of oxidative phosphorylation mainly affect the tissues characterized by a high-energy metabolism, such as nervous, cardiac and skeletal muscle tissues. In this review, we focus on human diseases caused by altered expressions of ATP synthase genes of both mitochondrial and nuclear origin. Moreover, we describe the contribution of ATP synthase to the pathophysiological mechanisms of other human diseases such as cardiovascular, neurodegenerative diseases or neurocognitive disorders.

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