Term
| Which endogenous factors influence aging? |
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Definition
| mutations , chromosomal instability, epigenetic changes, protein misfolding |
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Term
| Which exogenous factors influence aging? |
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Definition
| diet, exercise, stress- free living, healthy living |
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Term
| What are the primary hallmarks of aging? |
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Definition
| Primary hallmarks = cause of aging = genomic instability, telomeres' shortening, epigenetic changes, loss of proteostasis |
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Term
| What are the antagonistic hallmarks of aging? |
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Definition
| Antagonistic hallmarks = responses for aging = deregulated nutrients sensing, mitochondrial disfunction, cellular senescent |
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Term
| What are the integrative hallmarks of aging? |
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Definition
| Integrative hallmarks = culprits of phenotype = stem cells exaustion, altered cell-cell communication |
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Term
| What are exogenous factors of genome instability? |
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Definition
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Term
| What are endogenous factors of genome instability? |
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Definition
ROS
replication errors
spontaneous reactions |
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Term
| What is possible DNA damage and how are they repaired? |
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Definition
telomere shortening - repaired with telomerase
base damage - repaired with base excision repair
adduct formation - repaired with nucleotide excision repair,translession dna synthesis interstand crosslink - repaired with homologus repair,nucleotide excision repair, translession dna synthesis
double strand break-repaired with nonhomologus end joining homologus repair
mismatch - repaired with mismatch repair |
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Term
| How cellular senescence affects aging? |
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Definition
YOUNG: cellular senescence prevents the proliferation of damaged cells,protecting from cancer and contributing to tissue homeostasis.
OLD: the pervasive damage and the deficient clearance of senescent cells result in their accumulation, and this has a number of deleterious effects on tissue homeostasis that contribute to aging |
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Term
| How stem cell exhaustion affects aging? |
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Definition
| Consequences of the exhaustion of hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), satellite cells, and intestinal epithelial stem cells (IESCs) are exemplified: anaemia, myelodysplasia |
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Term
| How stem altered intercellular communication affects aging? |
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Definition
Neuroendocrine dysfunction
Inflammation
Immunosenecence |
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Term
| What are the functions of nuclear lamina? |
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Definition
Maintain nuclear stability
Organize chromatin
Bind nuclear pore complexes,nuclear envelope proteins and transcription factors
Important for: nuclear stability, chromal organizaton, DNA replica1on, cell cycle progression |
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Term
| Posttranslational modifications of lamin A |
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Definition
Farnesylation, triggered by CSIM at the C end
SIM cleaved by ZMPSTE24
Cystein is carboxymethylated
ZMPSTE24 removes the terminal 15 amino acids and farnesyl group |
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Term
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Definition
Silent mutation in coding sequence (G608G)
Alternative splicing -> deletion of 50 aa
Farnesylation, triggered by CSIM at the C end
SIM cleaved by ZMPSTE24
Cystein is carboxymethylated
Deletion-> no site for ZMPSTE24 -> it does not remove farnesyl group |
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Term
| What are the consequences of progerin embedded into nuclear lamina? |
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Definition
| fragility, vulnerability to mechanical stresses and nuclear blebbing, disrupted interactions with other nuclear envelope proteins and their consequent mislocation,disorganization and loss of peripheral heterochromatin |
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Term
| Is progerin present in stem cells? |
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Definition
| No, appears only after differentiation |
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Term
| What is the therapy for HGPS? |
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Definition
| FTI’s inhibit an enzyme that is necessary to attach to the farnesyl group to the progerin protein. If the farnesyl group can not be attached then the progerin protein can not fully function because in order to damage the cells and cause accelerated aging the progerin protein needs to be farnesylated. |
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Term
| Which protein telomers are bound to? What is its function? |
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Definition
| Telomeres are bound by a characteristic multiprotein complex - shelterin. A main function of this complex is to prevent the access of DNA repair proteins to the telomeres. |
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Term
| What absence of telomerase is leading to? |
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Definition
| Premature ageing and also in a lesser incidence of cancer |
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Term
| What overexpression of telomerase is leading to? |
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Definition
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Term
| What overexpression of telomerase together with cancer supressors is leading to? |
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Definition
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Term
| What are the possible fates of unfolded proteins? |
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Definition
| Autophagy, proteosomal degrdation, refolded protein thought chaperones or aggregation(aging) |
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Term
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Definition
constitutively decrease — extends longevity (lower rates of cell growth and metabolism and, hence, lower rates of cellular damage)
decrease is common during ageing
most conserved aging-controlling pathway in evolution |
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Term
| What happens with methylation during aging? |
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Definition
| global hypomethylation, but regional hypermethylaton |
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Term
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Definition
| NAD+-dependent deacetylases that target histone and nonhistone proteins |
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Term
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Definition
Senescent
Survival
DNA repair
Metabolism
Prolifiration |
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Term
| When sirtuin is more active? |
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Definition
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