Age-related changes in stem cell dynamics, neurogenesis, apoptosis, and gliosis in the adult brain: A novel teleost fish model of negligible senescence

2013 ◽  
Vol 74 (5) ◽  
pp. 514-530 ◽  
Author(s):  
Ian M. Traniello ◽  
Ruxandra F. Sîrbulescu ◽  
Iulian Ilieş ◽  
Günther K.H. Zupanc
Keyword(s):  
Stem Cell ◽  
Teleost Fish ◽  
Adult Brain ◽  
Cell Dynamics ◽  
Fish Model ◽  
Age Related ◽  
Negligible Senescence ◽  
Age Related Changes

scholarly journals Quantifying Microsatellite Mutation Rates from Intestinal Stem Cell Dynamics in Msh2-Deficient Murine Epithelium

Genetics ◽  
2019 ◽  
Vol 212 (3) ◽  
pp. 655-665 ◽  
Author(s):  
Joseph Christopher ◽  
Ann-Sofie Thorsen ◽  
Sam Abujudeh ◽  
Filipe C. Lourenço ◽  
Richard Kemp ◽  
...  
Keyword(s):  
Stem Cell ◽  
Fold Increase ◽  
Mutation Rates ◽  
Wild Type ◽  
Cell Dynamics ◽  
Tissue Samples ◽  
Age Related ◽  
Increased Risk ◽  
Microsatellite Mutation ◽  
Risk Of Cancer

Microsatellite sequences have an enhanced susceptibility to mutation, and can act as sentinels indicating elevated mutation rates and increased risk of cancer. The probability of mutant fixation within the intestinal epithelium is dictated by a combination of stem cell dynamics and mutation rate. Here, we exploit this relationship to infer microsatellite mutation rates. First a sensitive, multiplexed, and quantitative method for detecting somatic changes in microsatellite length was developed that allowed the parallel detection of mutant [CA]n sequences from hundreds of low-input tissue samples at up to 14 loci. The method was applied to colonic crypts in Mus musculus, and enabled detection of mutant subclones down to 20% of the cellularity of the crypt (∼50 of 250 cells). By quantifying age-related increases in clone frequencies for multiple loci, microsatellite mutation rates in wild-type and Msh2-deficient epithelium were established. An average 388-fold increase in mutation per mitosis rate was observed in Msh2-deficient epithelium (2.4 × 10−2) compared to wild-type epithelium (6.2 × 10−5).

scholarly journals The Diverse Roles of TIMP-3: Insights into Degenerative Diseases of the Senescent Retina and Brain

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 39 ◽  
Author(s):  
Dewing ◽  
Carare ◽  
Lotery ◽  
Ratnayaka
Keyword(s):  
Stem Cell ◽  
Age Related Macular Degeneration ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Degenerative Diseases ◽  
Risk Alleles ◽  
Age Related ◽  
New Treatments ◽  
Extracellular Environment ◽  
Age Related Changes

Tissue inhibitor of metalloproteinase-3 (TIMP-3) is a component of the extracellular environment, where it mediates diverse processes including matrix regulation/turnover, inflammation and angiogenesis. Rare TIMP-3 risk alleles and mutations are directly linked with retinopathies such as age-related macular degeneration (AMD) and Sorsby fundus dystrophy, and potentially, through indirect mechanisms, with Alzheimer’s disease. Insights into TIMP-3 activities may be gleaned from studying Sorsby-linked mutations. However, recent findings do not fully support the prevailing hypothesis that a gain of function through the dimerisation of mutated TIMP-3 is responsible for retinopathy. Findings from Alzheimer’s patients suggest a hitherto poorly studied relationship between TIMP-3 and the Alzheimer’s-linked amyloid-beta (A) proteins that warrant further scrutiny. This may also have implications for understanding AMD as aged/diseased retinae contain high levels of A. Findings from TIMP-3 knockout and mutant knock-in mice have not led to new treatments, particularly as the latter does not satisfactorily recapitulate the Sorsby phenotype. However, recent advances in stem cell and in vitro approaches offer novel insights into understanding TIMP-3 pathology in the retina-brain axis, which has so far not been collectively examined. We propose that TIMP-3 activities could extend beyond its hitherto supposed functions to cause age-related changes and disease in these organs.

scholarly journals Age-Related Changes in Methylome and Transcriptome of Hematopotietic Stem Cells Underlie Natural Genetic Variations

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2660-2660
Author(s):  
Ying Liang
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Stem Cell ◽  
Aging Process ◽  
Expression Patterns ◽  
Genetic Variations ◽  
Cell Aging ◽  
Hematopoietic Stem ◽  
Age Related ◽  
Age Related Changes

The aging of hematopoietic stem cells (HSCs) contributes to the aging of blood system and perhaps the whole organism. The aging process is coordinately determined by both genetic and epigenetic factors, and demonstrates inter-individual variations. We used high-throughput sequencing methods to study the age-dependent changes of genome-wide DNA methylation and gene expression patterns in HSCs of C57BL/6 (B6) and DBA/2 mouse strains, which have shown natural variations in HSC aging process. We observed global age-associated decrease of DNA methylation in both strains, but D2 HSCs have a stronger loss of epigenetic control than B6 stem cells during aging. Majority age-related changes of DNA methylation occur from young to mid-aged stages. We identified stable strain-specific differentially methylated regions (DMRs) that overlap with cis-eQTLs. Moreover, transcription factor binding site motifs are more likely to be disrupted in the DMRs, suggesting the potential impact of genetic variations on epigenetic regulation of HSC aging. We further demonstrated that strain-specific DMRs have more profound effects on the aging of B6 HSCs than D2 stem cells. Transposons are differentially regulated by the DMRs in the two strains, in which D2 HSCs are prone to transposon insertion. This study comprehensively investigated the effects of natural genetic and epigenetic variations on HSC aging. Loss of DNA methylation is an epigenetic signature of stem cell aging, and DNA methylation variations correlates with genetic variations, both contributing to inter-individual differences in stem cell and perhaps organismal aging. Disclosures No relevant conflicts of interest to declare.

Age-Related Changes to the Subventricular Zone Stem Cell Niche

2015 ◽  
pp. 35-68
Author(s):  
Matthew B. Eastman ◽  
Rebecca L. Acabchuk ◽  
Joanne C. Conover
Keyword(s):  
Stem Cell ◽  
Subventricular Zone ◽  
Stem Cell Niche ◽  
Age Related ◽  
Cell Niche ◽  
Age Related Changes

scholarly journals An NRF2 Perspective on Stem Cells and Ageing

2021 ◽  
Vol 2 ◽  
Author(s):  
Matthew Dodson ◽  
Annadurai Anandhan ◽  
Donna D. Zhang ◽  
Lalitha Madhavan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Brain Plasticity ◽  
Adult Brain ◽  
Cellular Redox ◽  
Age Related ◽  
Regenerative Activity ◽  
And Function ◽  
Stem Cell State

Redox and metabolic mechanisms lie at the heart of stem cell survival and regenerative activity. NRF2 is a major transcriptional controller of cellular redox and metabolic homeostasis, which has also been implicated in ageing and lifespan regulation. However, NRF2’s role in stem cells and their functioning with age is only just emerging. Here, focusing mainly on neural stem cells, which are core to adult brain plasticity and function, we review recent findings that identify NRF2 as a fundamental player in stem cell biology and ageing. We also discuss NRF2-based molecular programs that may govern stem cell state and function with age, and implications of this for age-related pathologies.

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