scholarly journals Klotho Deficiency Accelerates Stem Cells Aging by Impairing Telomerase Activity

2018 ◽  
Vol 74 (9) ◽  
pp. 1396-1407 ◽  
Author(s):  
Mujib Ullah ◽  
Zhongjie Sun
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Critical Role ◽  
Telomerase Activity ◽  
Cell Aging ◽  
Treated Animal ◽  
Differentiation Potential ◽  
Telomere Shortening ◽  
Altered Expression ◽  
Stem Cell Aging

Abstract Understanding the effect of molecular pathways involved in the age-dependent deterioration of stem cell function is critical for developing new therapies. The overexpression of Klotho (KL), an antiaging protein, causes treated animal models to enjoy extended life spans. Now, the question stands: Does KL deficiency accelerate stem cell aging and telomere shortening? If so, what are the specific mechanisms by which it does this, and is cycloastragenol (CAG) treatment enough to restore telomerase activity in aged stem cells? We found that KL deficiency diminished telomerase activity by altering the expression of TERF1 and TERT, causing impaired differentiation potential, pluripotency, cellular senescence, and apoptosis in stem cells. Telomerase activity decreased with KL-siRNA knockdown. This suggests that both KL and telomeres regulate the stem cell aging process through telomerase subunits TERF1, POT1, and TERT using the TGFβ, Insulin, and Wnt signaling. These pathways can rejuvenate stem cell populations in a CD90-dependent mechanism. Stem cell dysfunctions were largely provoked by KL deficiency and telomere shortening, owing to altered expression of TERF1, TGFβ1, CD90, POT1, TERT, and basic fibroblast growth factor (bFGF). The CAG treatment partially rescued telomerase deterioration, suggesting that KL plays a critical role in life-extension by regulating telomere length and telomerase activity.

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.

Metabolic Regulation and Related Molecular Mechanisms in Various Stem Cell Functions

2020 ◽  
Vol 15 (6) ◽  
pp. 531-546 ◽  
Author(s):  
Hwa-Yong Lee ◽  
In-Sun Hong
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Oxidative Phosphorylation ◽  
Metabolic Pathways ◽  
Critical Role ◽  
The Self ◽  
Specific Cell ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Cell Functions

Recent studies on the mechanisms that link metabolic changes with stem cell fate have deepened our understanding of how specific metabolic pathways can regulate various stem cell functions during the development of an organism. Although it was originally thought to be merely a consequence of the specific cell state, metabolism is currently known to play a critical role in regulating the self-renewal capacity, differentiation potential, and quiescence of stem cells. Many studies in recent years have revealed that metabolic pathways regulate various stem cell behaviors (e.g., selfrenewal, migration, and differentiation) by modulating energy production through glycolysis or oxidative phosphorylation and by regulating the generation of metabolites, which can modulate multiple signaling pathways. Therefore, a more comprehensive understanding of stem cell metabolism could allow us to establish optimal culture conditions and differentiation methods that would increase stem cell expansion and function for cell-based therapies. However, little is known about how metabolic pathways regulate various stem cell functions. In this context, we review the current advances in metabolic research that have revealed functional roles for mitochondrial oxidative phosphorylation, anaerobic glycolysis, and oxidative stress during the self-renewal, differentiation and aging of various adult stem cell types. These approaches could provide novel strategies for the development of metabolic or pharmacological therapies to promote the regenerative potential of stem cells and subsequently promote their therapeutic utility.

scholarly journals DYRK1A Negatively Regulates CDK5-SOX2 Pathway and Self-Renewal of Glioblastoma Stem Cells

2021 ◽  
Vol 22 (8) ◽  
pp. 4011
Author(s):  
Brianna Chen ◽  
Dylan McCuaig-Walton ◽  
Sean Tan ◽  
Andrew P. Montgomery ◽  
Bryan W. Day ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Critical Role ◽  
Stem Cell Differentiation ◽  
Neural Progenitor Cell ◽  
Cellular Heterogeneity ◽  
Differentiation Potential ◽  
Glioblastoma Stem Cells ◽  
Glioblastoma Stem Cell

Glioblastoma display vast cellular heterogeneity, with glioblastoma stem cells (GSCs) at the apex. The critical role of GSCs in tumour growth and resistance to therapy highlights the need to delineate mechanisms that control stemness and differentiation potential of GSC. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) regulates neural progenitor cell differentiation, but its role in cancer stem cell differentiation is largely unknown. Herein, we demonstrate that DYRK1A kinase is crucial for the differentiation commitment of glioblastoma stem cells. DYRK1A inhibition insulates the self-renewing population of GSCs from potent differentiation-inducing signals. Mechanistically, we show that DYRK1A promotes differentiation and limits stemness acquisition via deactivation of CDK5, an unconventional kinase recently described as an oncogene. DYRK1A-dependent inactivation of CDK5 results in decreased expression of the stemness gene SOX2 and promotes the commitment of GSC to differentiate. Our investigations of the novel DYRK1A-CDK5-SOX2 pathway provide further insights into the mechanisms underlying glioblastoma stem cell maintenance.

Serine Metabolism Controls Dental Pulp Stem Cell Aging by Regulating the DNA Methylation of p16

2020 ◽  
Vol 100 (1) ◽  
pp. 90-97
Author(s):  
R.L. Yang ◽  
H.M. Huang ◽  
C.S. Han ◽  
S.J. Cui ◽  
Y.K. Zhou ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Stem Cell ◽  
Dental Pulp ◽  
Permanent Teeth ◽  
Deciduous Teeth ◽  
Cell Aging ◽  
Differentiation Capacity ◽  
Stem Cell Aging ◽  
Serine Metabolism

To investigate the characteristics and molecular events of dental pulp stem cells (DPSCs) for tissue regeneration with aging, we isolated and analyzed the stem cells from human exfoliated deciduous teeth (SHED) and permanent teeth of young (Y-DPSCs) and old (A-DPSCs) adults. Results showed that the stemness and osteogenic differentiation capacity of DPSCs decreased with aging. The RNA sequencing results showed that glycine, serine, and threonine metabolism was one of the most enriched gene clusters among SHED, Y-DPSCs, and A-DPSCs, according to analysis based on the Kyoto Encyclopedia of Genes and Genomes. The expression of serine metabolism–related enzymes phosphoserine aminotransferase 1 (PSAT1) and phosphoglycerate (PHGDH) decreased in A-DPSCs and provided less methyl donor S-adenosylmethionine (SAM) for DNA methylation, leading to the hypomethylation of the senescence marker p16 (CDNK2A). Furthermore, the proliferation and differentiation capacity of Y-DPSCs and SHED decreased after PHGDH siRNA treatment, which reduced the level of SAM. Convincingly, the ratios of PSAT1-, PHGDH-, or proliferating cell nuclear antigen–positive cells in the dental pulp of old permanent teeth were less than those in the dental pulp of deciduous teeth and young permanent teeth. In summary, the stemness and differentiation capacity of DPSCs decreased with aging. The decreased serine metabolism in A-DPSCs upregulated the expression of p16 via attenuating its DNA methylation, resulting in DPSC aging. Our finding indicated that serine metabolism and 1 carbon unit participated in stem cell aging, which provided new direction for stem cell aging study and intervention.

Caloric restriction maintains stem cells through niche and regulates stem cell aging

2019 ◽  
Vol 98 (1) ◽  
pp. 25-37 ◽  
Author(s):  
Nagarajan Maharajan ◽  
Karthikeyan Vijayakumar ◽  
Chul Ho Jang ◽  
Goang-Won Cho
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Caloric Restriction ◽  
Cell Aging ◽  
Stem Cell Aging

scholarly journals Investigation of Stem Cell Aging Throughout the Lifetime and Therapeutic Opportunities

2020 ◽  
Author(s):  
Sarah Karimi ◽  
Setareh Raoufi ◽  
Zohreh Bagher
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Aging Process ◽  
Cell Function ◽  
Cell Activity ◽  
The Body ◽  
Natural Phenomenon ◽  
Cell Aging ◽  
Molecular Pathways ◽  
Stem Cell Aging

Introduction: Aging is a natural phenomenon that is caused by changes in the cells of the body. Theoretically, aging starts from birth and lasts throughout life. These changes affect the function of the cells. Also, in old tissues, the capacity for homeostasis and tissue repair is decline due to destructive changes in specific tissue stem cells, niche of stem cells and systemic factors that regulate stem cell activity. Understanding molecular pathways that disrupt stem cell function during aging is crucial for the development of new treatments for aging-associated diseases. In this article, the symptoms of stem cell aging and the key molecular pathways that are commonly used for the aging of stem cells were discussed. We will consider experimental evidence for all of the mechanisms and evaluate the way that can slow down or even stop the aging process. Finally, we will look at the aging process of three types of stem cells.

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.

Stem Cell Senescence: the Obstacle of the Treatment of Degenerative Disk Disease

2019 ◽  
Vol 14 (8) ◽  
pp. 654-668 ◽  
Author(s):  
Ying Chen ◽  
Liling Tang
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Senescence ◽  
Cell Aging ◽  
Limiting Factor ◽  
Low Back ◽  
The Family ◽  
Stem Cell Aging ◽  
Negative Effect ◽  
Ivd Degeneration

Intervertebral disc (IVD) has a pivotal role in the maintenance of flexible motion. IVD degeneration is one of the primary causes of low back pain and disability, which seriously influences patients’ health, and increases the family and social economic burden. Recently, stem cell therapy has been proven to be more effective on IVD degeneration disease. However, stem cell senescence is the limiting factor in the IVD degeneration treatment. Senescent stem cells have a negative effect on the self-repair on IVD degeneration. In this review, we delineate that the factors such as telomerase shortening, DNA damage, oxidative stress, microenvironment and exosomes will induce stem cell aging. Recent studies tried to delay the aging of stem cells by regulating the expression of aging-related genes and proteins, changing the activity of telomerase, improving the survival microenvironment of stem cells and drug treatment. Understanding the mechanism of stem cell aging and exploring new approaches to delay or reverse stem cell aging asks for research on the repair of the degenerated disc.

Identification of Candidate Regulators of Hematopoietic Stem Cell Aging Using a Combined QTL Mapping and Microarray Analysis Approach.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1722-1722
Author(s):  
Erin J. Oakley ◽  
Gary Van Zant
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Qtl Mapping ◽  
Hematopoietic Stem Cell ◽  
Differentially Expressed ◽  
Cell Aging ◽  
Chromosome 2 ◽  
Hematopoietic Stem ◽  
Congenic Mice ◽  
Stem Cell Aging

Abstract A combination of quantitative trait locus (QTL) mapping and microarray expression profiling was used to identify five novel candidate genes for regulating hematopoietic stem cell aging in two strains of inbred mice, C57BL/6 (B6) and DBA/2 (D2). Despite their ability to self-renew and maintain essentially normal levels of hematopoietic function throughout the lifetime of an organism, it has become increasingly evident that hematopoietic stem cells (HSCs) are subject to qualitative and quantitative changes over time, and that these changes may affect both the rate of aging and longevity of organisms. In mice, the effect of aging on stem cells is highly strain-specific, thus suggesting that genetic regulation plays a role in HSC aging. Our lab has identified a QTL on murine chromosome 2 that is associated with the variation in frequency of HSCs between aged B6 and D2 mice. In B6 mice, the frequency of HSCs increases with age, whereas in D2 mice the population of HSCs decreases as the animals age. Using a congenic mouse model in which the region surrounding the QTL in D2 mice was introgressed onto a B6 background, genome wide gene expression analyses were performed using sorted lineage negative hematopoietic cells, which are enriched for primitive stem and progenitor hematopoietic cells. RNA isolated from lineage negative cells from chromosome 2 congenic and B6 background mice at young and old ages was reverse transcribed, labeled, and hybridized to Affymetrix Murine Genome 430 arrays. Using an overall p-value cut-off of ≤ 0.01, a total of 4,368 transcripts were differentially expressed between background and congenic mice, out of 39,000 transcripts present on the mouse genome chip. Following a ‘QTL to Gene’ strategy, we identified 123 differentially expressed transcripts located in the congenic interval on chromosome 2. We then assessed for hematopoietic tissue specific expression patterns, the presence of single nucleotide polymorphisms (SNPs) in the transcripts, and cis-regulation of transcript expression. Five genes were identified that met these criteria, and thus are considered candidate regulators of hematopoietic stem cell aging. We used real time PCR to validate differential expression of a subset of the identified genes. Interestingly, a majority of the genes are associated with cell cycle control and/or protein targeting and transport processes. Additionally, all five cis-regulated genes were found to be down-regulated in aged congenic mice compared to aged B6 mice, thus suggesting coordinated regulation by a common promoter region(s) located within the chromosome 2 QTL. These findings suggest that stem cell aging is associated with specifc intrinsic cellular events and provide insight into the genetic mechanisms underlying hematopoietic stem cell aging.

Sign in / Sign up

Export Citation Format

Share Document