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

Christine Hansel; Verena Jendrossek; Diana Klein

doi:10.3390/ijms21093279

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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Diverse Roles of Cellular Senescence in Skeletal Muscle Inflammation, Regeneration, and Therapeutics

Frontiers in Pharmacology ◽

10.3389/fphar.2021.739510 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yuki Saito ◽

Takako S. Chikenji

Keyword(s):

Skeletal Muscle ◽

Cellular Senescence ◽

Current Knowledge ◽

Inflammatory Diseases ◽

Neuromuscular Disorders ◽

Muscle Stem Cells ◽

Related Disease ◽

Tissue Degeneration ◽

Cycle Arrest ◽

Age Related

Skeletal muscle undergoes vigorous tissue remodeling after injury. However, aging, chronic inflammatory diseases, sarcopenia, and neuromuscular disorders cause muscle loss and degeneration, resulting in muscular dysfunction. Cellular senescence, a state of irreversible cell cycle arrest, acts during normal embryonic development and remodeling after tissue damage; when these processes are complete, the senescent cells are eliminated. However, the accumulation of senescent cells is a hallmark of aging tissues or pathological contexts and may lead to progressive tissue degeneration. The mechanisms responsible for the effects of senescent cells have not been fully elucidated. Here, we review current knowledge about the beneficial and detrimental effects of senescent cells in tissue repair, regeneration, aging, and age-related disease, especially in skeletal muscle. We also discuss how senescence of muscle stem cells and muscle-resident fibro-adipogenic progenitors affects muscle pathologies or regeneration, and consider the possibility that immunosenescence leads to muscle pathogenesis. Finally, we explore senotherapy, the therapeutic targeting of senescence to treat age-related disease, from the standpoint of improving muscle regeneration.

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Cellular Senescence: Aging, Cancer, and Injury

Physiological Reviews ◽

10.1152/physrev.00020.2018 ◽

2019 ◽

Vol 99 (2) ◽

pp. 1047-1078 ◽

Cited By ~ 85

Author(s):

Arianna Calcinotto ◽

Jaskaren Kohli ◽

Elena Zagato ◽

Laura Pellegrini ◽

Marco Demaria ◽

...

Keyword(s):

Cell Cycle ◽

Cellular Senescence ◽

Defense Mechanism ◽

Tissue Remodeling ◽

Proliferating Cells ◽

Positive Role ◽

Cellular Defense ◽

Cycle Arrest ◽

Key Features

Cellular senescence is a permanent state of cell cycle arrest that occurs in proliferating cells subjected to different stresses. Senescence is, therefore, a cellular defense mechanism that prevents the cells to acquire an unnecessary damage. The senescent state is accompanied by a failure to re-enter the cell cycle in response to mitogenic stimuli, an enhanced secretory phenotype and resistance to cell death. Senescence takes place in several tissues during different physiological and pathological processes such as tissue remodeling, injury, cancer, and aging. Although senescence is one of the causative processes of aging and it is responsible of aging-related disorders, senescent cells can also play a positive role. In embryogenesis and tissue remodeling, senescent cells are required for the proper development of the embryo and tissue repair. In cancer, senescence works as a potent barrier to prevent tumorigenesis. Therefore, the identification and characterization of key features of senescence, the induction of senescence in cancer cells, or the elimination of senescent cells by pharmacological interventions in aging tissues is gaining consideration in several fields of research. Here, we describe the known key features of senescence, the cell-autonomous, and noncell-autonomous regulators of senescence, and we attempt to discuss the functional role of this fundamental process in different contexts in light of the development of novel therapeutic targets.

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Cellular Senescence in Liver Disease and Regeneration

Seminars in Liver Disease ◽

10.1055/s-0040-1722262 ◽

2021 ◽

Author(s):

Sofia Ferreira-Gonzalez ◽

Daniel Rodrigo-Torres ◽

Victoria L. Gadd ◽

Stuart J. Forbes

Keyword(s):

Cell Cycle ◽

Liver Disease ◽

Cell Cycle Arrest ◽

Genomic Instability ◽

Cellular Senescence ◽

Cell Populations ◽

Cycle Arrest ◽

Relevant Role ◽

Extent Of Damage

AbstractCellular senescence is an irreversible cell cycle arrest implemented by the cell as a result of stressful insults. Characterized by phenotypic alterations, including secretome changes and genomic instability, senescence is capable of exerting both detrimental and beneficial processes. Accumulating evidence has shown that cellular senescence plays a relevant role in the occurrence and development of liver disease, as a mechanism to contain damage and promote regeneration, but also characterizing the onset and correlating with the extent of damage. The evidence of senescent mechanisms acting on the cell populations of the liver will be described including the role of markers to detect cellular senescence. Overall, this review intends to summarize the role of senescence in liver homeostasis, injury, disease, and regeneration.

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Role of Age-Related Mitochondrial Dysfunction in Sarcopenia

International Journal of Molecular Sciences ◽

10.3390/ijms21155236 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5236 ◽

Cited By ~ 1

Author(s):

Evelyn Ferri ◽

Emanuele Marzetti ◽

Riccardo Calvani ◽

Anna Picca ◽

Matteo Cesari ◽

...

Keyword(s):

Skeletal Muscle ◽

Cellular Senescence ◽

Significant Loss ◽

Muscle Aging ◽

Age Related ◽

Mitochondrial Functions ◽

Health Quality ◽

Skeletal Muscle Aging ◽

And Function

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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Chronic Inflammation as an Immunological Abnormality and Effectiveness of Exercise

Biomolecules ◽

10.3390/biom9060223 ◽

2019 ◽

Vol 9 (6) ◽

pp. 223 ◽

Cited By ~ 21

Author(s):

Katsuhiko Suzuki

Keyword(s):

Chronic Inflammation ◽

Pathological Condition ◽

Inflammatory Cells ◽

The Elderly ◽

Healthy Life ◽

Daily Lives ◽

Food Ingredients ◽

Tissue Degeneration ◽

Age Related

Reduced levels of physical activity in people’s daily lives cause the development of metabolic syndromes or age-related disorders. Chronic inflammation is now understood to be an underlying pathological condition in which inflammatory cells such as neutrophils and monocyte/macrophages infiltrate into fat and other tissues and accumulate when people become obese due to overeating and/or physical inactivity. Pro-inflammatory mediators such as cytokines that are secreted in excess from inflammatory cells will not only lead to the development of arteriosclerosis when they chronically affect blood vessels but also bring tissue degeneration and/or dysfunction to various organs. Chronic inflammation is also involved in sarcopenia that brings hypofunction in the elderly, dementia, osteoporosis, or cancer and negatively affects many chronic diseases and people’s healthy life expectancy. In this paper, outlines of such studies are introduced in terms of homeostatic inflammation, which occurs chronically due to the innate immune system and its abnormalities, while focusing on the efficacy of exercise from aspects of immunology and oxidative stress. The preventative effects of functional food ingredients in combination with exercise are also introduced and described. The challenges and future directions in understanding the role of exercise in the control of chronic inflammation are discussed.

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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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ROLE OF AMALAKYADI RASAYANA IN LOWERING DOWN THE MORBIDITY RATE IN CHILDREN: A REVIEW

International Journal of Research in Ayurveda and Pharmacy ◽

10.7897/2277-4343.1105153 ◽

2020 ◽

Vol 11 (5) ◽

pp. 121-127

Author(s):

Ajay Kushwaha ◽

Nisha Kumari Ojha

Keyword(s):

Immune System ◽

Experimental Studies ◽

Anthelmintic Activity ◽

The Body ◽

Morbidity Rate ◽

Tissue Quality ◽

Tissue Degeneration ◽

Age Related

Children are more susceptible to various infections because of underdeveloped immune system as compared to adults. Strengthening the immune system is a natural way to help the body fight against the disease-causing pathogens and immunomodulators can play a major role in this context. Various Ayurveda classics and studies published in journals related to Ayurveda drugs for improving immunity are reviewed and analysed. In Ayurveda, the objective of immune enhancement is achieved through the use of the Amalakyadi Rasayana (an Immunomodulators), as it increases longevity of life, memory, intellect, luxture, complexion, voice, strength of the body functions, strength of all senses and provides the resistance to disease, improves glow and power. Analysis of classical references and various experimental studies show that Amalakyadi Rasayana posse immuno-modulatory, Antioxidant, Anti-inflammatory, Antimicrobial, Anthelmintic activity. Present paper is a review to update knowledge on pharmacological properties, therapeutic actions and possible mode of action of the selected formulation, Amalakyadi rasayana from Yogaratnakara (Rasayanadhikara/17) to enhance the immunity in children. Rasayana is an important part of Ayurvedic therapeutics used to improve the quality of life by strengthening the tissue quality and by reducing the age-related tissue degeneration. This study reveals that Amalakyadi Rasayana have potential to improve or strengthen the immune system in children and thereby can lower down the morbidity rate in children.

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