The role of microRNAs in cellular senescence and age-related conditions of cartilage and bone

Skeletal muscle aging is associated with a significant loss of skeletal muscle strength and power (i.e., dynapenia), muscle mass and quality of life, a phenomenon known as sarcopenia. This condition affects nearly one-third of the older population and is one of the main factors leading to negative health outcomes in geriatric patients. Notwithstanding the exact mechanisms responsible for sarcopenia are not fully understood, mitochondria have emerged as one of the central regulators of sarcopenia. In fact, there is a wide consensus on the assumption that the loss of mitochondrial integrity in myocytes is the main factor leading to muscle degeneration. Mitochondria are also key players in senescence. It has been largely proven that the modulation of mitochondrial functions can induce the death of senescent cells and that removal of senescent cells improves musculoskeletal health, quality, and function. In this review, the crosstalk among mitochondria, cellular senescence, and sarcopenia will be discussed with the aim to elucidate the role that the musculoskeletal cellular senescence may play in the onset of sarcopenia through the mediation of mitochondria.

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What have we learned from basic science studies on idiopathic pulmonary fibrosis?

European Respiratory Review ◽

10.1183/16000617.0029-2019 ◽

2019 ◽

Vol 28 (153) ◽

pp. 190029 ◽

Cited By ~ 5

Author(s):

Toyoshi Yanagihara ◽

Seidai Sato ◽

Chandak Upagupta ◽

Martin Kolb

Keyword(s):

Extracellular Matrix ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Cellular Senescence ◽

Basic Science ◽

Science Studies ◽

Cell Types ◽

Age Related ◽

Tremendous Progress

Idiopathic pulmonary fibrosis is a fatal age-related lung disease characterised by progressive and irreversible scarring of the lung. Although the details are not fully understood, there has been tremendous progress in understanding the pathogenesis of idiopathic pulmonary fibrosis, which has led to the identification of many new potential therapeutic targets. In this review we discuss several of these advances with a focus on genetic susceptibility and cellular senescence primarily affecting epithelial cells, activation of profibrotic pathways, disease-enhancing fibrogenic cell types and the role of the remodelled extracellular matrix.

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Senescence and Cancer: Role of Nitric Oxide (NO) in SASP

Cancers ◽

10.3390/cancers12051145 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1145

Author(s):

Nesrine Mabrouk ◽

Silvia Ghione ◽

Véronique Laurens ◽

Stéphanie Plenchette ◽

Ali Bettaieb ◽

...

Keyword(s):

Nitric Oxide ◽

Cancer Treatment ◽

Cellular Senescence ◽

Negative Effects ◽

No Donors ◽

Cell State ◽

Age Related ◽

A Cell ◽

Secretory Phenotype

Cellular senescence is a cell state involved in both physiological and pathological processes such as age-related diseases and cancer. While the mechanism of senescence is now well known, its role in tumorigenesis still remains very controversial. The positive and negative effects of senescence on tumorigenesis depend largely on the diversity of the senescent phenotypes and, more precisely, on the senescence-associated secretory phenotype (SASP). In this review, we discuss the modulatory effect of nitric oxide (NO) in SASP and the possible benefits of the use of NO donors or iNOS inducers in combination with senotherapy in cancer treatment.

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DNA damage responses in ageing

Open Biology ◽

10.1098/rsob.190168 ◽

2019 ◽

Vol 9 (11) ◽

pp. 190168 ◽

Cited By ~ 10

Author(s):

Paulo F. L. da Silva ◽

Björn Schumacher

Keyword(s):

Dna Damage ◽

Stress Response ◽

Cellular Senescence ◽

Damage Accumulation ◽

Genome Instability ◽

Age Related ◽

Progeroid Syndromes ◽

Dna Damage Responses ◽

Universal Feature

Ageing appears to be a nearly universal feature of life, ranging from unicellular microorganisms to humans. Longevity depends on the maintenance of cellular functionality, and an organism's ability to respond to stress has been linked to functional maintenance and longevity. Stress response pathways might indeed become therapeutic targets of therapies aimed at extending the healthy lifespan. Various progeroid syndromes have been linked to genome instability, indicating an important causal role of DNA damage accumulation in the ageing process and the development of age-related pathologies. Recently, non-cell-autonomous mechanisms including the systemic consequences of cellular senescence have been implicated in regulating organismal ageing. We discuss here the role of cellular and systemic mechanisms of ageing and their role in ageing-associated diseases.

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Ageing, Cellular Senescence and Neurodegenerative Disease

International Journal of Molecular Sciences ◽

10.3390/ijms19102937 ◽

2018 ◽

Vol 19 (10) ◽

pp. 2937 ◽

Cited By ~ 59

Author(s):

Marios Kritsilis ◽

Sophia V. Rizou ◽

Paraskevi Koutsoudaki ◽

Konstantinos Evangelou ◽

Vassilis Gorgoulis ◽

...

Keyword(s):

Multiple Sclerosis ◽

Neurodegenerative Disease ◽

Cellular Senescence ◽

Biological Process ◽

The Novel ◽

Cell Type ◽

Age Related ◽

Cell Type Specific ◽

First Time

Ageing is a major risk factor for developing many neurodegenerative diseases. Cellular senescence is a homeostatic biological process that has a key role in driving ageing. There is evidence that senescent cells accumulate in the nervous system with ageing and neurodegenerative disease and may predispose a person to the appearance of a neurodegenerative condition or may aggravate its course. Research into senescence has long been hindered by its variable and cell-type specific features and the lack of a universal marker to unequivocally detect senescent cells. Recent advances in senescence markers and genetically modified animal models have boosted our knowledge on the role of cellular senescence in ageing and age-related disease. The aim now is to fully elucidate its role in neurodegeneration in order to efficiently and safely exploit cellular senescence as a therapeutic target. Here, we review evidence of cellular senescence in neurons and glial cells and we discuss its putative role in Alzheimer’s disease, Parkinson’s disease and multiple sclerosis and we provide, for the first time, evidence of senescence in neurons and glia in multiple sclerosis, using the novel GL13 lipofuscin stain as a marker of cellular senescence.

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Cellular Senescence in Bone

10.5772/intechopen.101803 ◽

2021 ◽

Author(s):

Danielle Wang ◽

Haitao Wang

Keyword(s):

Cellular Senescence ◽

Bone Diseases ◽

Epigenetic Alterations ◽

Pharmacological Interventions ◽

Telomere Attrition ◽

Cycle Arrest ◽

Age Related ◽

The Common ◽

Common Problems

Senescence is an irreversible cell-cycle arrest process induced by environmental, genetic, and epigenetic factors. An accumulation of senescent cells in bone results in age-related disorders, and one of the common problems is osteoporosis. Deciphering the basic mechanisms contributing to the chronic ailments of aging may uncover new avenues for targeted treatment. This review focuses on the mechanisms and the most relevant research advancements in skeletal cellular senescence. To identify new options for the treatment or prevention of age-related chronic diseases, researchers have targeted hallmarks of aging, including telomere attrition, genomic instability, cellular senescence, and epigenetic alterations. First, this chapter provides an overview of the fundamentals of bone tissue, the causes of skeletal involution, and the role of cellular senescence in bone and bone diseases such as osteoporosis. Next, this review will discuss the utilization of pharmacological interventions in aging tissues and, more specifically, highlight the role of senescent cells to identify the most effective and safe strategies.

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Cellular Senescence in the Lung: The Central Role of Senescent Epithelial Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21093279 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3279 ◽

Cited By ~ 2

Author(s):

Christine Hansel ◽

Verena Jendrossek ◽

Diana Klein

Keyword(s):

Cell Cycle ◽

Cellular Senescence ◽

Inflammatory Diseases ◽

Cancer Tissue ◽

Gene Expressions ◽

Proliferating Cells ◽

Differentiated Cells ◽

Tissue Degeneration ◽

Age Related

Cellular senescence is a key process in physiological dysfunction developing upon aging or following diverse stressors including ionizing radiation. It describes the state of a permanent cell cycle arrest, in which proliferating cells become resistant to growth-stimulating factors. Senescent cells differ from quiescent cells, which can re-enter the cell cycle and from finally differentiated cells: morphological and metabolic changes, restructuring of chromatin, changes in gene expressions and the appropriation of an inflammation-promoting phenotype, called the senescence-associated secretory phenotype (SASP), characterize cellular senescence. The biological role of senescence is complex, since both protective and harmful effects have been described for senescent cells. While initially described as a mechanism to avoid malignant transformation of damaged cells, senescence can even contribute to many age-related diseases, including cancer, tissue degeneration, and inflammatory diseases, particularly when senescent cells persist in damaged tissues. Due to overwhelming evidence about the important contribution of cellular senescence to the pathogenesis of different lung diseases, specific targeting of senescent cells or of pathology-promoting SASP factors has been suggested as a potential therapeutic approach. In this review, we summarize recent advances regarding the role of cellular (fibroblastic, endothelial, and epithelial) senescence in lung pathologies, with a focus on radiation-induced senescence. Among the different cells here, a central role of epithelial senescence is suggested.

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Cholesterol biosynthetic pathway induces cellular senescence through ERRa

10.1101/2021.10.20.465100 ◽

2021 ◽

Author(s):

Dorian V Ziegler ◽

Mathieu Vernier ◽

Joanna Czarnecka-Herok ◽

Charlotte Scholtes ◽

Christelle Machon ◽

...

Keyword(s):

Cellular Senescence ◽

Biosynthetic Pathway ◽

Mevalonate Pathway ◽

Cholesterol Biosynthesis ◽

Age Related ◽

Diet Regimen ◽

Cholesterol Biosynthetic Pathway ◽

A Cell ◽

Normal Human

Cellular senescence is a cell program induced by various stresses that leads to a stable proliferation arrest and to a senescence-associated secretory phenotype. Accumulation of senescent cells during age-related diseases participates in these pathologies and regulates healthy lifespan. Recent evidences point out a global dysregulated intracellular metabolism associated to senescence phenotype. Nonetheless, the functional contribution of metabolic homeostasis in regulating senescence is barely understood. In this work, we describe how the mevalonate pathway, an anabolic pathway leading to the endogenous biosynthesis of poly-isoprenoids, such as cholesterol, acts as a positive regulator of cellular senescence in normal human cells. Mechanistically, this mevalonate-induced senescence is partly mediated by the downstream cholesterol biosynthetic pathway. This pathway promotes transcriptional activity of ERRα leading to dysfunctional mitochondria, ROS production, DNA damage and a p53-dependent senescence. Supporting the relevance of these observations, increase of senescence in liver due to a high-fat diet regimen is abrogated in ERRα knockout mouse. Overall, this work unravels the role of cholesterol biosynthesis in the induction of an ERRα-dependent mitochondrial program leading to cellular senescence and related pathological alterations.

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nc886, a Non-Coding RNA, Is a New Biomarker and Epigenetic Mediator of Cellular Senescence in Fibroblasts

International Journal of Molecular Sciences ◽

10.3390/ijms222413673 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13673

Author(s):

Yuna Kim ◽

Hyanggi Ji ◽

Eunae Cho ◽

Nok-Hyun Park ◽

Kyeonghwan Hwang ◽

...

Keyword(s):

Cellular Senescence ◽

Replicative Senescence ◽

Tumor Formation ◽

Epigenetic Changes ◽

Functional Studies ◽

Human Models ◽

Age Related ◽

Non Coding Rna ◽

Epigenetic Regulators

Functional studies of organisms and human models have revealed that epigenetic changes can significantly impact the process of aging. Non-coding RNA (ncRNA), one of epigenetic regulators, plays an important role in modifying the expression of mRNAs and their proteins. It can mediate the phenotype of cells. It has been reported that nc886 (=vtRNA2-1 or pre-miR-886), a long ncRNA, can suppress tumor formation and photo-damages of keratinocytes caused by UVB. The aim of this study was to determine the role of nc886 in replicative senescence of fibroblasts and determine whether substances capable of controlling nc886 expression could regulate cellular senescence. In replicative senescence fibroblasts, nc886 expression was decreased while methylated nc886 was increased. There were changes of senescence biomarkers including SA-β-gal activity and expression of p16INK4A and p21Waf1/Cip1 in senescent cells. These findings indicate that the decrease of nc886 associated with aging is related to cellular senescence of fibroblasts and that increasing nc886 expression has potential to suppress cellular senescence. AbsoluTea Concentrate 2.0 (ATC) increased nc886 expression and ameliorated cellular senescence of fibroblasts by inhibiting age-related biomarkers. These results indicate that nc886 has potential as a new target for anti-aging and that ATC can be a potent epigenetic anti-aging ingredient.

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The Emerging Role of Senescence in Ocular Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/2583601 ◽

2020 ◽

Vol 2020 ◽

pp. 1-19 ◽

Cited By ~ 4

Author(s):

Parameswaran G. Sreekumar ◽

David R. Hinton ◽

Ram Kannan

Keyword(s):

Cellular Senescence ◽

Age Related Macular Degeneration ◽

Bioactive Molecules ◽

Surrounding Tissue ◽

New Members ◽

Age Related ◽

Reasonable Evidence ◽

Aging Mechanisms ◽

Cellular Stresses

Cellular senescence is a state of irreversible cell cycle arrest in response to an array of cellular stresses. An important role for senescence has been shown for a number of pathophysiological conditions that include cardiovascular disease, pulmonary fibrosis, and diseases of the skin. However, whether senescence contributes to the progression of age-related macular degeneration (AMD) has not been studied in detail so far and the present review describes the recent research on this topic. We present an overview of the types of senescence, pathways of senescence, senescence-associated secretory phenotype (SASP), the role of mitochondria, and their functional implications along with antisenescent therapies. As a central mechanism, senescent cells can impact the surrounding tissue microenvironment via the secretion of a pool of bioactive molecules, termed the SASP. An updated summary of a number of new members of the ever-growing SASP family is presented. Further, we introduce the significance of mechanisms by which mitochondria may participate in the development of cellular senescence. Emerging evidence shows that extracellular vesicles (EVs) are important mediators of the effects of senescent cells on their microenvironment. Based on recent studies, there is reasonable evidence that senescence could be a modifiable factor, and hence, it may be possible to delay age-related diseases by modulating basic aging mechanisms using SASP inhibitors/senolytic drugs. Thus, antisenescent therapies in aging and age-related diseases appear to have a promising potential.

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