New insights into skin stem cell aging and cancer

2014 ◽  
Vol 42 (3) ◽  
pp. 663-669 ◽  
Author(s):  
M. Carmen Ortells ◽  
William M. Keyes
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Cell Aging ◽  
Adult Tissue ◽  
Self Renewal ◽  
Tissue Specific ◽  
Regulatory Processes ◽  
Age Related ◽  
Stem Cell Aging ◽  
Growth Properties

Adult tissue homoeostasis requires continual replacement of cells that are lost due to normal turnover, injury and disease. However, aging is associated with an overall decline in tissue function and homoeostasis, suggesting that the normal regulatory processes that govern self-renewal and regeneration may become impaired with age. Tissue-specific SCs (stem cells) lie at the apex of organismal conservation and regeneration, ultimately being responsible for continued tissue maintenance. In many tissues, there are changes in SC numbers, or alteration of their growth properties during aging, often involving imbalances in tumour-suppressor- and oncogene-mediated pathways. Uncovering the molecular mechanisms leading to changes in SC function during aging will provide an essential tool to address tissue-specific age-related pathologies. In the present review, we summarize the age-related alterations found in different tissue SC populations, highlighting recently identified changes in aged HFSCs (hair-follicle SCs) in the skin.

scholarly journals Intestinal Stem Cell Aging: Origins and Interventions

2020 ◽  
Vol 82 (1) ◽  
pp. 203-226 ◽  
Author(s):  
Heinrich Jasper
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Intestinal Stem Cells ◽  
Intestinal Stem Cell ◽  
Cell Aging ◽  
Control Mechanisms ◽  
Regenerative Processes ◽  
Age Related ◽  
Stem Cell Aging ◽  
Multicellular Organisms

Regenerative processes that maintain the function of the gastrointestinal (GI) epithelium are critical for health and survival of multicellular organisms. In insects and vertebrates, intestinal stem cells (ISCs) regenerate the GI epithelium. ISC function is regulated by intrinsic, local, and systemic stimuli to adjust regeneration to tissue demands. These control mechanisms decline with age, resulting in significant perturbation of intestinal homeostasis. Processes that lead to this decline have been explored intensively in Drosophila melanogaster in recent years and are now starting to be characterized in mammalian models. This review presents a model for age-related regenerative decline in the fly intestine and discusses recent findings that start to establish molecular mechanisms of age-related decline of mammalian ISC function.

scholarly journals Aging of hematopoietic stem cells

Blood ◽  
2018 ◽  
Vol 131 (5) ◽  
pp. 479-487 ◽  
Author(s):  
Gerald de Haan ◽  
Seka Simone Lazare
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Blood Cells ◽  
Aging Process ◽  
Molecular Mechanisms ◽  
Cell Aging ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Stem Cell Aging

Abstract Hematopoietic stem cells (HSCs) ensure a balanced production of all blood cells throughout life. As they age, HSCs gradually lose their self-renewal and regenerative potential, whereas the occurrence of cellular derailment strongly increases. Here we review our current understanding of the molecular mechanisms that contribute to HSC aging. We argue that most of the causes that underlie HSC aging result from cell-intrinsic pathways, and reflect on which aspects of the aging process may be reversible. Because many hematological pathologies are strongly age-associated, strategies to intervene in aspects of the stem cell aging process may have significant clinical relevance.

scholarly journals Stem Cell Quiescence versus Senescence: The Key for Healthy Aging

2021 ◽  
Vol 13 (4) ◽  
pp. 337-49
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Healthy Aging ◽  
Molecular Mechanisms ◽  
Adult Stem Cell ◽  
Cell Aging ◽  
Tissue Specific ◽  
Age Related ◽  
Cell Decline ◽  
Tissue Specific Stem Cells

BACKGROUND: Aging tissues lose their homeostatic and regenerative capacities, which has been linked to the degeneration of the stem cells such as the tissue-specific stem cells, the stem cell niches, and systemic cues that regulate stem cell activity.CONTENT: The maintenance of tissue homeostatic and regeneration dependent on its tissue-specific stem cells, that —long-lived cells with the ability to self-renew and differentiate into mature cells. Understanding the molecular mechanisms that governs stem cell survival, self-renewal, quiescence, proliferation, and commitment to specific differentiated cell lineages is critical for identifying the drivers and effectors of age-associated stem cell failure. Such understanding will be critical for the development of therapeutic approaches that can decrease, and possibly reverse and repair the age-related degenerative process in aging tissues.SUMMARY: The exact mechanisms and reasons of aging process were not fully elucidated until now. Stem cells is one of the keys for maintaining tissues heath and understanding how stem cell decline with age will give us opportunities to find strategy in increasing somatic stem cells regenerative capacity and delay the aging process.KEYWORDS: adult stem cell, aging, epigenetic, metabolism, quiescence, senescence

scholarly journals Causes and Mechanisms of Hematopoietic Stem Cell Aging

2019 ◽  
Vol 20 (6) ◽  
pp. 1272 ◽  
Author(s):  
Jungwoon Lee ◽  
Suk Yoon ◽  
Inpyo Choi ◽  
Haiyoung Jung
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
The Elderly ◽  
Cell Aging ◽  
Extrinsic Factors ◽  
Hematopoietic Stem ◽  
Age Related ◽  
Stem Cell Aging ◽  
Related Stress

Many elderly people suffer from hematological diseases known to be highly age-dependent. Hematopoietic stem cells (HSCs) maintain the immune system by producing all blood cells throughout the lifetime of an organism. Recent reports have suggested that HSCs are susceptible to age-related stress and gradually lose their self-renewal and regeneration capacity with aging. HSC aging is driven by cell-intrinsic and -extrinsic factors that result in the disruption of the immune system. Thus, the study of HSC aging is important to our understanding of age-related immune diseases and can also provide potential strategies to improve quality of life in the elderly. In this review, we delineate our understanding of the phenotypes, causes, and molecular mechanisms involved in HSC aging.

scholarly journals Manifestations and mechanisms of stem cell aging

2011 ◽  
Vol 193 (2) ◽  
pp. 257-266 ◽  
Author(s):  
Ling Liu ◽  
Thomas A. Rando
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Cell Aging ◽  
Functional Changes ◽  
Cell Based Therapy ◽  
Age Related ◽  
Stem Cell Aging ◽  
Genetic Interventions ◽  
Cell Functionality

Adult stem cells exist in most mammalian organs and tissues and are indispensable for normal tissue homeostasis and repair. In most tissues, there is an age-related decline in stem cell functionality but not a depletion of stem cells. Such functional changes reflect deleterious effects of age on the genome, epigenome, and proteome, some of which arise cell autonomously and others of which are imposed by an age-related change in the local milieu or systemic environment. Notably, some of the changes, particularly epigenomic and proteomic, are potentially reversible, and both environmental and genetic interventions can result in the rejuvenation of aged stem cells. Such findings have profound implications for the stem cell–based therapy of age-related diseases.

scholarly journals Non-Coding RNAs Steering the Senescence-Related Progress, Properties, and Application of Mesenchymal Stem Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Jingyi Cai ◽  
Hexu Qi ◽  
Ke Yao ◽  
Yang Yao ◽  
Dian Jing ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Cellular Senescence ◽  
The Other ◽  
Skeletal System ◽  
Self Renewal ◽  
Regulatory Processes ◽  
Age Related ◽  
Non Coding Rnas

The thirst to postpone and even reverse aging progress has never been quenched after all these decades. Unequivocally, mesenchymal stem cells (MSCs), with extraordinary abilities such as self-renewal and multi-directional differentiation, deserve the limelight in this topic. Though having several affable clinical traits, MSCs going through senescence would, on one hand, contribute to age-related diseases and, on the other hand, lead to compromised or even counterproductive therapeutical outcomes. Notably, increasing evidence suggests that non-coding RNAs (ncRNAs) could invigorate various regulatory processes. With even a slight dip or an uptick of expression, ncRNAs would make a dent in or even overturn cellular fate. Thereby, a systematic illustration of ncRNAs identified so far to steer MSCs during senescence is axiomatically an urgent need. In this review, we introduce the general properties and mechanisms of senescence and its relationship with MSCs and illustrate the ncRNAs playing a role in the cellular senescence of MSCs. It is then followed by the elucidation of ncRNAs embodied in extracellular vesicles connecting senescent MSCs with other cells and diversified processes in and beyond the skeletal system. Last, we provide a glimpse into the clinical methodologies of ncRNA-based therapies in MSC-related fields. Hopefully, the intricate relationship between senescence and MSCs will be revealed one day and our work could be a crucial stepping-stone toward that future.

scholarly journals Mitochondrial Dysfunction in Stem Cell Aging

2015 ◽  
Vol 7 (1) ◽  
pp. 15
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mitochondrial Dysfunction ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Tissue Homeostasis ◽  
Cell Aging ◽  
Aging Research ◽  
Age Related

BACKGROUND: Regardless of the precise underlying molecular mechanisms, the fundamental defining manifestation of aging is an overall decline in the functional capacity of various organs to maintain baseline tissue homeostasis and to respond adequately to physiological needs under stress. There is an increasingly urgent need for a more complete understanding of the molecular pathways and biological processes underlying aging and age-related disorders.CONTENT: Mitochondria constitute the most prominent source of adenosine triphosphate (ATP) and are implicated in multiple anabolic and catabolic circuitries. In addition, mitochondria coordinate cell-wide stress responses and control non-apoptotic cell death routines. The involvement of mitochondria in both vital and lethal processes is crucial for both embryonic and postembryonic development, as well as for the maintenance of adult tissue homeostasis. Age-associated telomere damage, diminution of telomere ‘capping’ function and associated p53 activation have emerged as prime instigators of a functional decline of tissue stem cells and of mitochondrial dysfunction that adversely affect renewal and bioenergetic support in diverse tissues. Constructing a model of how telomeres, stem cells and mitochondria interact with key molecules governing genome integrity, ‘stemness’ and metabolism provides a framework for how diverse factors contribute to aging and age-related disorders.SUMMARY: Cellular senescence defined as an irreversible proliferation arrest promotes age-related decline in mammalian tissue homeostasis. The aging of tissue-specific stem cell and progenitor cell compartments is believed to be central to the decline of tissue and organ integrity and function in the elderly. Taken into consideration that the overwhelming majority of intracellular reactive oxygen species (ROS) are of mitochondrial origin, it is reasonable to posit that the elevated ROS production might be caused by alteration in mitochondrial function during senescence. It is likely that mitochondria and stem cells will remain at the forefront of aging research also for the next decade.KEYWORDS: aging, stem cell, mitochondrial biogenesis, mitophagy, senescence, telomeres

scholarly journals The Mechanism of Stem Cell Aging

2022 ◽  
Author(s):  
Liangyu Mi ◽  
Junping Hu ◽  
Na Li ◽  
Jinfang Gao ◽  
Rongxiu Huo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Cell Aging ◽  
Therapeutic Application ◽  
Differentiation Potential ◽  
Stem Cell Aging ◽  
New Directions ◽  
Aging Mechanisms

AbstractStem cells have self-renewal ability and multi-directional differentiation potential. They have tissue repair capabilities and are essential for maintaining the tissue homeostasis. The depletion of stem cells is closely related to the occurrence of body aging and aging-related diseases. Therefore, revealing the molecular mechanisms of stem cell aging will set new directions for the therapeutic application of stem cells, the study of aging mechanisms, and the prevention and treatment of aging-related diseases. This review comprehensively describes the molecular mechanisms related to stem cell aging and provides the basis for further investigations aimed at developing new anti-stem cell aging strategies and promoting the clinical application of stem cells.

scholarly journals Stem Cells: The Future Promise of Stem Cells in Healthspan

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 742-743
Author(s):  
Ashley Webb
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Aging ◽  
Hematopoietic System ◽  
Tissue Specific ◽  
Maintenance And Repair ◽  
Stem Cell Aging ◽  
The Future ◽  
Tissue Specific Stem Cells

Abstract Tissue specific stem cells are critical for maintenance and repair of tissues and organs throughout life. However, during aging, the functionality of stem cells declines, contributing to tissue decline. This symposium will focus on the mechanisms underlying stem cell aging in various compartments, including muscle, brain and the hematopoietic system.

scholarly journals Local anesthetics impair the growth and self-renewal of glioblastoma stem cells by inhibiting ZDHHC15-mediated GP130 palmitoylation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiaoqing Fan ◽  
Haoran Yang ◽  
Chenggang Zhao ◽  
Lizhu Hu ◽  
Delong Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Western Blot ◽  
Local Anesthetics ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Xenograft Model ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Self Renewal

Abstract Background A large number of preclinical studies have shown that local anesthetics have a direct inhibitory effect on tumor biological activities, including cell survival, proliferation, migration, and invasion. There are few studies on the role of local anesthetics in cancer stem cells. This study aimed to determine the possible role of local anesthetics in glioblastoma stem cell (GSC) self-renewal and the underlying molecular mechanisms. Methods The effects of local anesthetics in GSCs were investigated through in vitro and in vivo assays (i.e., Cell Counting Kit 8, spheroidal formation assay, double immunofluorescence, western blot, and xenograft model). The acyl-biotin exchange method (ABE) assay was identified proteins that are S-acylated by zinc finger Asp-His-His-Cys-type palmitoyltransferase 15 (ZDHHC15). Western blot, co-immunoprecipitation, and liquid chromatograph mass spectrometer-mass spectrometry assays were used to explore the mechanisms of ZDHHC15 in effects of local anesthetics in GSCs. Results In this study, we identified a novel mechanism through which local anesthetics can damage the malignant phenotype of glioma. We found that local anesthetics prilocaine, lidocaine, procaine, and ropivacaine can impair the survival and self-renewal of GSCs, especially the classic glioblastoma subtype. These findings suggest that local anesthetics may weaken ZDHHC15 transcripts and decrease GP130 palmitoylation levels and membrane localization, thus inhibiting the activation of IL-6/STAT3 signaling. Conclusions In conclusion, our work emphasizes that ZDHHC15 is a candidate therapeutic target, and local anesthetics are potential therapeutic options for glioblastoma.

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