Lipid Players of Cellular Senescence

Lipids are emerging as key players of senescence. Here, we review the exciting new findings on the diverse roles of lipids in cellular senescence, most of which are enabled by the advancements in omics approaches. Senescence is a cellular process in which the cell undergoes growth arrest while retaining metabolic activity. At the organismal level, senescence contributes to organismal aging and has been linked to numerous diseases. Current research has documented that senescent cells exhibit global alterations in lipid composition, leading to extensive morphological changes through membrane remodeling. Moreover, senescent cells adopt a secretory phenotype, releasing various components to their environment that can affect the surrounding tissue and induce an inflammatory response. All of these changes are membrane and, thus, lipid related. Our work, and that of others, has revealed that fatty acids, sphingolipids, and glycerolipids are involved in the initiation and maintenance of senescence and its associated inflammatory components. These studies opened up an exciting frontier to investigate the deeper mechanistic understanding of the regulation and function of these lipids in senescence. In this review, we will provide a comprehensive snapshot of the current state of the field and share our enthusiasm for the prospect of potential lipid-related protein targets for small-molecule therapy in pathologies involving senescence and its related inflammatory phenotypes.

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Skin Aging, Cellular Senescence and Natural Polyphenols

International Journal of Molecular Sciences ◽

10.3390/ijms222312641 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12641

Author(s):

Erika Csekes ◽

Lucia Račková

Keyword(s):

Cellular Senescence ◽

Skin Aging ◽

The Body ◽

Skin Changes ◽

Natural Polyphenols ◽

Current State ◽

Age Related ◽

Aged Skin ◽

And Function

The skin, being the barrier organ of the body, is constitutively exposed to various stimuli impacting its morphology and function. Senescent cells have been found to accumulate with age and may contribute to age-related skin changes and pathologies. Natural polyphenols exert many health benefits, including ameliorative effects on skin aging. By affecting molecular pathways of senescence, polyphenols are able to prevent or delay the senescence formation and, consequently, avoid or ameliorate aging and age-associated pathologies of the skin. This review aims to provide an overview of the current state of knowledge in skin aging and cellular senescence, and to summarize the recent in vitro studies related to the anti-senescent mechanisms of natural polyphenols carried out on keratinocytes, melanocytes and fibroblasts. Aged skin in the context of the COVID-19 pandemic will be also discussed.

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Control of Mesenchymal Stromal Cell Senescence by Tryptophan Metabolites

International Journal of Molecular Sciences ◽

10.3390/ijms22020697 ◽

2021 ◽

Vol 22 (2) ◽

pp. 697

Author(s):

Kenneth K. Wu

Keyword(s):

Cellular Senescence ◽

Morphological Changes ◽

Aerobic Glycolysis ◽

Mapk Signaling ◽

Ros Generation ◽

New Class ◽

Age Related ◽

Tryptophan Metabolites ◽

Mesenchymal Stromal Stem Cell ◽

And Function

Cellular senescence contributes to aging and age-related disorders. High glucose (HG) induces mesenchymal stromal/stem cell (MSC) senescence, which hampers cell expansion and impairs MSC function. Intracellular HG triggers metabolic shift from aerobic glycolysis to oxidative phosphorylation, resulting in reactive oxygen species (ROS) overproduction. It causes mitochondrial dysfunction and morphological changes. Tryptophan metabolites such as 5-methoxytryptophan (5-MTP) and melatonin attenuate HG-induced MSC senescence by protecting mitochondrial integrity and function and reducing ROS generation. They upregulate the expression of antioxidant enzymes. Both metabolites inhibit stress-induced MSC senescence by blocking p38 MAPK signaling pathway, NF-κB, and p300 histone acetyltransferase activity. Furthermore, melatonin upregulates SIRT-1, which reduces NF-κB activity by de-acetylation of NF-κB subunits. Melatonin and 5-MTP are a new class of metabolites protecting MSCs against replicative and stress-induced cellular senescence. They provide new strategies to improve the efficiency of MSC-based therapy for diverse human diseases.

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The Oxford Handbook of the Auditory Brainstem

10.1093/oxfordhb/9780190849061.001.0001 ◽

2018 ◽

Cited By ~ 1

Keyword(s):

Current Knowledge ◽

Auditory Pathway ◽

Auditory Brainstem ◽

Auditory Midbrain ◽

Current State ◽

Neuronal Mechanisms ◽

Maladaptive Plasticity ◽

And Function ◽

Auditory Field

The Oxford Handbook of the Auditory Brainstem provides an in-depth reference to the organization and function of ascending and descending auditory pathways in the mammalian brainstem. Individual chapters are organized along the auditory pathway, beginning with the cochlea and ending with the auditory midbrain. Each chapter provides an introduction to the respective area and summarizes our current knowledge before discussing the disputes and challenges that the field currently faces.The handbook emphasizes the numerous forms of plasticity that are increasingly observed in many areas of the auditory brainstem. Several chapters focus on neuronal modulation of function and plasticity on the synaptic, neuronal, and circuit level, especially during development, aging, and following peripheral hearing loss. In addition, the book addresses the role of trauma-induced maladaptive plasticity with respect to its contribution in generating central hearing dysfunction, such as hyperacusis and tinnitus.The book is intended for students and postdoctoral fellows starting in the auditory field and for researchers of related fields who wish to get an authoritative and up-to-date summary of the current state of auditory brainstem research. For clinical practitioners in audiology, otolaryngology, and neurology, the book is a valuable resource of information about the neuronal mechanisms that are currently discussed as major candidates for the generation of central hearing dysfunction.

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From Exosome Glycobiology to Exosome Glycotechnology, the Role of Natural Occurring Polysaccharides

Polysaccharides ◽

10.3390/polysaccharides2020021 ◽

2021 ◽

Vol 2 (2) ◽

pp. 311-338

Author(s):

Giulia Della Rosa ◽

Clarissa Ruggeri ◽

Alessandra Aloisi

Keyword(s):

State Of The Art ◽

Cell Communication ◽

Pathological Conditions ◽

New Findings ◽

Cell Type Specific ◽

New Perspective ◽

And Function ◽

And Personalized Medicine ◽

Innate Ability

Exosomes (EXOs) are nano-sized informative shuttles acting as endogenous mediators of cell-to-cell communication. Their innate ability to target specific cells and deliver functional cargo is recently claimed as a promising theranostic strategy. The glycan profile, actively involved in the EXO biogenesis, release, sorting and function, is highly cell type-specific and frequently altered in pathological conditions. Therefore, the modulation of EXO glyco-composition has recently been considered an attractive tool in the design of novel therapeutics. In addition to the available approaches involving conventional glyco-engineering, soft technology is becoming more and more attractive for better exploiting EXO glycan tasks and optimizing EXO delivery platforms. This review, first, explores the main functions of EXO glycans and associates the potential implications of the reported new findings across the nanomedicine applications. The state-of-the-art of the last decade concerning the role of natural polysaccharides—as targeting molecules and in 3D soft structure manufacture matrices—is then analysed and highlighted, as an advancing EXO biofunction toolkit. The promising results, integrating the biopolymers area to the EXO-based bio-nanofabrication and bio-nanotechnology field, lay the foundation for further investigation and offer a new perspective in drug delivery and personalized medicine progress.

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Cellular Senescence and Mammalian Healthspan

Innovation in Aging ◽

10.1093/geroni/igaa057.2655 ◽

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.

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Flavonoids in Skin Senescence Prevention and Treatment

International Journal of Molecular Sciences ◽

10.3390/ijms22136814 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6814

Author(s):

Anna Domaszewska-Szostek ◽

Monika Puzianowska-Kuźnicka ◽

Alina Kuryłowicz

Keyword(s):

Therapeutic Strategy ◽

Cancer Susceptibility ◽

Skin Aging ◽

Structure And Function ◽

Tissue Structure ◽

Delayed Wound Healing ◽

Secretory Phenotype ◽

Cellular Pathways ◽

And Function ◽

Increased Susceptibility

Skin aging is associated with the accumulation of senescent cells and is related to many pathological changes, including decreased protection against pathogens, increased susceptibility to irritation, delayed wound healing, and increased cancer susceptibility. Senescent cells secrete a specific set of pro-inflammatory mediators, referred to as a senescence-associated secretory phenotype (SASP), which can cause profound changes in tissue structure and function. Thus, drugs that selectively eliminate senescent cells (senolytics) or neutralize SASP (senostatics) represent an attractive therapeutic strategy for age-associated skin deterioration. There is growing evidence that plant-derived compounds (flavonoids) can slow down or even prevent aging-associated deterioration of skin appearance and function by targeting cellular pathways crucial for regulating cellular senescence and SASP. This review summarizes the senostatic and senolytic potential of flavonoids in the context of preventing skin aging.

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Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 Signaling

Cells ◽

10.3390/cells10010063 ◽

2021 ◽

Vol 10 (1) ◽

pp. 63

Author(s):

Ji Hye Kwon ◽

Miyeon Kim ◽

Soyoun Um ◽

Hyang Ju Lee ◽

Yun Kyung Bae ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cellular Senescence ◽

Small Cells ◽

Critical Determinant ◽

Senescent Phenotype ◽

Toll Like Receptor 2 ◽

Secretory Phenotype ◽

Major Factors

In order to provide a sufficient number of cells for clinical use, mesenchymal stem cells (MSCs) must be cultured for long-term expansion, which inevitably triggers cellular senescence. Although the small size of MSCs is known as a critical determinant of their fate, the main regulators of stem cell senescence and the underlying signaling have not been addressed. Umbilical cord blood-derived MSCs (UCB-MSCs) were obtained using size-isolation methods and then cultured with control or small cells to investigate the major factors that modulate MSC senescence. Cytokine array data suggested that the secretion of interukin-8 (IL-8) or growth-regulated oncogene-alpha (GROa) by senescent cells was markedly inhibited during incubation of small cells along with suppression of cognate receptor (C-X-C motif chemokine receptor2, CXCR2) via blockade of the autocrine/paracrine positive loop. Moreover, signaling via toll-like receptor 2 (TLR2) and TLR5, both pattern recognition receptors, drove cellular senescence of MSCs, but was inhibited in small cells. The activation of TLRs (2 and 5) through ligand treatment induced a senescent phenotype in small cells. Collectively, our data suggest that small cell from UCB-MSCs exhibit delayed cellular senescence by inhibiting the process of TLR signaling-mediated senescence-associated secretory phenotype (SASP) activation.

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Expression and Function of Organic Anion Transporting Polypeptides in the Human Brain: Physiological and Pharmacological Implications

Pharmaceutics ◽

10.3390/pharmaceutics13060834 ◽

2021 ◽

Vol 13 (6) ◽

pp. 834

Author(s):

Anima M. Schäfer ◽

Henriette E. Meyer zu Schwabedissen ◽

Markus Grube

Keyword(s):

Organic Anion ◽

Physiological Role ◽

Point Of View ◽

Efflux Transporters ◽

Organic Anion Transporting Polypeptides ◽

Current State ◽

P Glycoprotein ◽

The Central Nervous System ◽

And Function ◽

Uptake Transporters

The central nervous system (CNS) is an important pharmacological target, but it is very effectively protected by the blood–brain barrier (BBB), thereby impairing the efficacy of many potential active compounds as they are unable to cross this barrier. Among others, membranous efflux transporters like P-Glycoprotein are involved in the integrity of this barrier. In addition to these, however, uptake transporters have also been found to selectively uptake certain compounds into the CNS. These transporters are localized in the BBB as well as in neurons or in the choroid plexus. Among them, from a pharmacological point of view, representatives of the organic anion transporting polypeptides (OATPs) are of particular interest, as they mediate the cellular entry of a variety of different pharmaceutical compounds. Thus, OATPs in the BBB potentially offer the possibility of CNS targeting approaches. For these purposes, a profound understanding of the expression and localization of these transporters is crucial. This review therefore summarizes the current state of knowledge of the expression and localization of OATPs in the CNS, gives an overview of their possible physiological role, and outlines their possible pharmacological relevance using selected examples.

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Exploring the microbiome in health and disease

Toxicology Research and Application ◽

10.1177/2397847317741884 ◽

2017 ◽

Vol 1 ◽

pp. 239784731774188 ◽

Cited By ~ 5

Author(s):

Elena Scotti ◽

Stéphanie Boué ◽

Giuseppe Lo Sasso ◽

Filippo Zanetti ◽

Vincenzo Belcastro ◽

...

Keyword(s):

Human Health ◽

Metabolic Diseases ◽

Skin Diseases ◽

Human Microbiome ◽

Chronic Obstructive ◽

Microbial Composition ◽

Obstructive Pulmonary Disease ◽

New Findings ◽

Dynamics And Function ◽

And Function

The analysis of human microbiome is an exciting and rapidly expanding field of research. In the past decade, the biological relevance of the microbiome for human health has become evident. Microbiome comprises a complex collection of microorganisms, with their genes and metabolites, colonizing different body niches. It is now well known that the microbiome interacts with its host, assisting in the bioconversion of nutrients and detoxification, supporting immunity, protecting against pathogenic microbes, and maintaining health. Remarkable new findings showed that our microbiome not only primarily affects the health and function of the gastrointestinal tract but also has a strong influence on general body health through its close interaction with the nervous system and the lung. Therefore, a perfect and sensitive balanced interaction of microbes with the host is required for a healthy body. In fact, growing evidence suggests that the dynamics and function of the indigenous microbiota can be influenced by many factors, including genetics, diet, age, and toxicological agents like cigarette smoke, environmental contaminants, and drugs. The disruption of this balance, that is called dysbiosis, is associated with a plethora of diseases, including metabolic diseases, inflammatory bowel disease, chronic obstructive pulmonary disease, periodontitis, skin diseases, and neurological disorders. The importance of the host microbiome for the human health has also led to the emergence of novel therapeutic approaches focused on the intentional manipulation of the microbiota, either by restoring missing functions or eliminating harmful roles. In the present review, we outline recent studies devoted to elucidate not only the role of microbiome in health conditions and the possible link with various types of diseases but also the influence of various toxicological factors on the microbial composition and function.

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Intestinal Structure and Function after Small Bowel by-Pass in the Rat

Clinical Science ◽

10.1042/cs0430731 ◽

1972 ◽

Vol 43 (6) ◽

pp. 731-742 ◽

Cited By ~ 101

Author(s):

M. H. Gleeson ◽

J. Cullen ◽

R. H. Dowling

Keyword(s):

Small Bowel ◽

Migration Rate ◽

Morphological Changes ◽

Intestinal Resection ◽

Glucose Absorption ◽

Turnover Time ◽

Structure And Function ◽

Major Influence ◽

Intestinal Continuity ◽

And Function

1. To study further the influence of luminal nutrition on small bowel structure and function, segments of rat jejunum and ileum were completely excluded from intestinal continuity by Thiry-Vella by-pass operations. The effect of partial deprivation of luminal nutrition was also studied in jejunal segments that had been surgically transposed to a distal position in the intestinal tract. 2. Macroscopically, by-passed jejunum and ileum both became narrowed and atrophic, whereas the intestine in continuity showed hypertrophic changes similar to those seen after intestinal resection. 3. In by-passed intestine the pattern of villi changed from mucosal ridges to ‘fingers’ and ‘leaves’. Although villous height and total mucosal thickness were both reduced, light microscopy showed that even 6 months after exclusion from intestinal continuity villous morphology was still retained. 4. Epithelial-cell migration rate and turnover time were diminished in both jejunum and ileum after by-pass. In intestine in continuity the migration rate was increased, but the turnover time remained the same as in controls. 5. In by-passed jejunum, in vivo glucose absorption diminished progressively with time, but did not change in excluded ileal segments. 6. After ileo-jejunal transposition, the jejunum showed no major morphological changes, but glucose absorption became significantly depressed. 7. These results further support the concept that intraluminal nutrition exerts a major influence on cell turnover, villous morphology and absorptive function in the small intestine.

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