Understanding Vascular Diseases: Lessons From Premature Aging Syndromes

2016 ◽  
Vol 32 (5) ◽  
pp. 650-658 ◽  
Author(s):  
Yuichi Ikeda ◽  
Hidetoshi Kumagai ◽  
Yoshihiro Motozawa ◽  
Jun-ichi Suzuki ◽  
Hiroshi Akazawa ◽  
...  
Keyword(s):  
Vascular Diseases ◽  
Premature Aging ◽  
Premature Aging Syndromes

Aging, cellular senescence and cancer: epigenetic alterations and nuclear remodeling

2019 ◽  
pp. 238-253
Author(s):  
John C. Lucchesi
Keyword(s):  
Histone Modifications ◽  
Cellular Senescence ◽  
Aging Process ◽  
Nuclear Architecture ◽  
Gene Mutations ◽  
Histone Variants ◽  
Premature Aging ◽  
Model Organisms ◽  
Premature Aging Syndromes ◽  
Nuclear Remodeling

Epigenetic modifications correlated with aging and oncogenesis are changes in the pattern of DNA methylation and of histone modifications, and changes in the level of histone variants (H3.3, macroH2A, H2A.Z) and gene mutations. The sirtuins are a set of highly conserved protein deacetylases of particular significance to the aging process. Many cancer types are found to carry mutations in chromatin-modifying genes such as those encoding methyl or acetyl transferases, affecting the histone modifications of promoters and enhancers. The aging process and oncogenesis present a number of changes in the nuclear architecture. Mutations in the lamina-coding genes lead to premature aging syndromes. Mutations in remodeling complexes are found in different cancers. Modifications that affect the architectural protein binding sites at topologically associating domain (TAD) borders can cause the merging of neighboring TADs. The levels of short non-coding RNAs (sncRNAs) are altered in model organisms and are associated with cancer. Changes in the position of chromosome territories often occur in tumor cells. Nevertheless, cellular senescence, due mostly to the absence of telomerase, represents a mechanism of tumor suppression.

O VI.3 Regulation of gene repair and transcription in normal human cells, and in premature aging syndromes

1997 ◽  
Vol 379 (1) ◽  
pp. S41
Author(s):  
Vilhelm A. Bohr ◽  
Adayabalam Balajce ◽  
Grigory Dianov ◽  
Amrita Machwe ◽  
Alfred May ◽  
...  
Keyword(s):  
Human Cells ◽  
Premature Aging ◽  
Gene Repair ◽  
Normal Human ◽  
Normal Human Cells ◽  
Premature Aging Syndromes

Human premature aging syndromes and genomic instability

2002 ◽  
Vol 123 (8) ◽  
pp. 987-993 ◽  
Author(s):  
Vilhelm A. Bohr
Keyword(s):  
Genomic Instability ◽  
Premature Aging ◽  
Premature Aging Syndromes

scholarly journals Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

2014 ◽  
Vol 29 ◽  
pp. 125-147 ◽  
Author(s):  
Pierre Cau ◽  
Claire Navarro ◽  
Karim Harhouri ◽  
Patrice Roll ◽  
Sabine Sigaudy ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Translational Research ◽  
Nuclear Matrix ◽  
Premature Aging ◽  
Research Perspective ◽  
Premature Aging Syndromes

scholarly journals PRDM8 reveals aberrant DNA methylation in aging syndromes and is relevant for hematopoietic and neuronal differentiation

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Olivia Cypris ◽  
Monika Eipel ◽  
Julia Franzen ◽  
Corinna Rösseler ◽  
Vithurithra Tharmapalan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bone Marrow ◽  
Neuronal Differentiation ◽  
Bone Marrow Failure ◽  
Premature Aging ◽  
Telomere Attrition ◽  
Bone Marrow Failure Syndromes ◽  
Epigenetic Age ◽  
Premature Aging Syndromes ◽  
Aberrant Dna Methylation

Abstract Background Dyskeratosis congenita (DKC) and idiopathic aplastic anemia (AA) are bone marrow failure syndromes that share characteristics of premature aging with severe telomere attrition. Aging is also reflected by DNA methylation changes, which can be utilized to predict donor age. There is evidence that such epigenetic age predictions are accelerated in premature aging syndromes, but it is yet unclear how this is related to telomere length. DNA methylation analysis may support diagnosis of DKC and AA, which still remains a challenge for these rare diseases. Results In this study, we analyzed blood samples of 70 AA and 18 DKC patients to demonstrate that their epigenetic age predictions are overall increased, albeit not directly correlated with telomere length. Aberrant DNA methylation was observed in the gene PRDM8 in DKC and AA as well as in other diseases with premature aging phenotype, such as Down syndrome and Hutchinson-Gilford-Progeria syndrome. Aberrant DNA methylation patterns were particularly found within subsets of cell populations in DKC and AA samples as measured with barcoded bisulfite amplicon sequencing (BBA-seq). To gain insight into the functional relevance of PRDM8, we used CRISPR/Cas9 technology to generate induced pluripotent stem cells (iPSCs) with heterozygous and homozygous knockout. Loss of PRDM8 impaired hematopoietic and neuronal differentiation of iPSCs, even in the heterozygous knockout clone, but it did not impact on epigenetic age. Conclusion Taken together, our results demonstrate that epigenetic aging is accelerated in DKC and AA, independent from telomere attrition. Furthermore, aberrant DNA methylation in PRDM8 provides another biomarker for bone marrow failure syndromes and modulation of this gene in cellular subsets may be related to the hematopoietic and neuronal phenotypes observed in premature aging syndromes. Graphical abstract

Genodermatoses with Premature Aging/Syndromes

2015 ◽  
pp. 1-19
Author(s):  
Adele Chedraoui ◽  
Abdul Ghani Kibbi ◽  
Mazen Kurban
Keyword(s):  
Premature Aging ◽  
Premature Aging Syndromes

Aneuploidy analysis in fibroblasts of human premature aging syndromes by FISH during in vitro cellular aging

1998 ◽  
Vol 103 (2) ◽  
pp. 209-222 ◽  
Author(s):  
Asit B Mukherjee ◽  
Christin Costello
Keyword(s):  
Cellular Aging ◽  
Premature Aging ◽  
Premature Aging Syndromes

scholarly journals Premature aging syndromes: From patients to mechanism

2019 ◽  
Vol 96 (2) ◽  
pp. 58-65
Author(s):  
Mattheus Xing Rong Foo ◽  
Peh Fern Ong ◽  
Oliver Dreesen
Keyword(s):  
Premature Aging ◽  
Premature Aging Syndromes

The Rb/E2F pathway and Ras activation regulate RecQ helicase gene expression

2008 ◽  
Vol 412 (2) ◽  
pp. 299-306 ◽  
Author(s):  
Yongqing Liu ◽  
Shahenda El-Naggar ◽  
Brian Clem ◽  
Jason Chesney ◽  
Douglas C. Dean
Keyword(s):  
Dna Replication ◽  
Family Members ◽  
Dna Helicase ◽  
Premature Aging ◽  
Telomere Maintenance ◽  
Ras Activation ◽  
Oncogenic Mutations ◽  
Helicase Gene ◽  
Cell Cycle Pathway ◽  
Premature Aging Syndromes

Disruption of the Rb (retinoblastoma protein)/E2F cell-cycle pathway and Ras activation are two of the most frequent events in cancer, and both of these mutations place oncogenic stress on cells to increase DNA replication. In the present study, we demonstrate that these mutations have an additive effect on induction of members of the RecQ DNA helicase family. RecQ activity is important for genomic stability, initiation of DNA replication and telomere maintenance, and mutation of the BLM (Bloom's syndrome gene), WRN (Werner's syndrome gene) or RECQL4 (Rothmund–Thomson syndrome gene) family members leads to premature aging syndromes characterized by genetic instability and telomere loss. RecQ family members are frequently overexpressed in cancers, and overexpression of BLM has been shown to cause telomere elongation. Concomitant with induction of RecQ genes in response to Rb family mutation and Ras activation, we show an increase in the number of telomeric repeats. We suggest that this induction of RecQ genes in response to common oncogenic mutations may explain the up-regulation of the genes seen in cancers, and it may provide a means for transformed cells to respond to an increased demand for DNA replication.

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