Cellular Aging And Death Flashcards
Induction of heat shock proteins occurs in which situation?
Damaged to intracellular proteins
What is Cellular senescence
An irreversible cell-cycle arrest mechanism
Acts to protect against cancer
Involved in development, tissue repair, aging and age related disorders.
What is Aging
An inevitable and progressive biological process
Tightly regulated and complex interplay between genetic and acquired factors
Aging is typically characterized by an increase in senescence
A quantitative and qualitative decrease in stem cells
Abnormal structure at tissue levels
Aging phenotypes in humans
Genome instability
Macro molecular aggregates
Decrease in innate immunity
Decreased mitochondrial function
Sarcopenia
Decrease fitness (Tonus of the cells)
Aging theories
RNA processing
Oxidative stress theory etc…
RNA processing
A key intermediary step between transcription and translation in the central dogma
- rna processing
-5 capping
-pre-mRNA splicing
-3-polyadenylation
-rna editing
Alternative splicing
Accounts for the complexity of organisms
Most of our pre-mRNAs shown to be alternatively spliced
Pre-mRNA splicing
Is an intricate posttranscriptional process
Leads to the removal of introns and joining of exons in a pre-mRNA to form a mature mRNA
Exon usage is increased by
Aging
Splicing changes corresponds to
Genes involved in aging including : DNA repair, DNA damage and apoptosis, neuronal plasticity
Signaling pathways of aging
Activation of the Sir2 pathway
IGF-1/mTOR pathway
Sir2 pathway
Silences transcription at silent mating loci,telomeres and the ribosomal DNA.
Extends replication life span
NAD+ dependent histone deacetylase
Catalyzes the cleavage of acetyl groups from lysine residues in multiple substrates
Its overexpression or induction in starvation leads to increased lifespan in Caenorhabditis Elegans and Drosophila melanogaster
Sir2 activators
Caloric restriction
Resveratrol
Who is involved in the deterioration of DNA and protein quality control
Ubiquitin
Chaperone
Lysosome
Proteasome
Ubiquilin 1
What causes aging and tissue degeneration
Glycation
Chemical damage due to oxidative stress
Addition of sugar residıues
Modify both DNA and proteins
Loss of vigor and decreased lifespan
Increased protein damage during aging exacerbated by a declining heat shock response
Reduced levels of heat shock protein
Resultant loss of protein quality control
Which HSP’s directly protect cells against damage-induced entry into death pathways
Hsp27
Hsp70
HSPs protect
Proteome
By folding denatured polypeptides and promoting the degradation of severely damaged proteins
HSF1 initiates what
Transcription factor (HSP1)
Initiates the prolactin induction of HSP when cells are exposed to protein damage
HSPs inhibitors of
Apoptosis (programmed cell death)
Heat Shock response declines in
Aging cell
HSP27
Acts as a protein chaperone and an antioxidant and plays a role in the inhibition of apoptosis and actin cytoskeletal remodeling
HSP70
Protein folding
With ATP
CHIP
Carboxyl terminus of HSP70-interacting protein
Bridges the molecular chaperone and ubiquitin-proteasome protein degradation systems
Contains a U binding domain
Bio markers of senescence
Cell cycle is arrested— activity of cyclin dependent kinase
Telomere attrition
Bio markers of transition to a senescent state
Heterochromatin foci (SAHF)
Secretome
SASP (senescence associated secretory phenotype)
Klotho
An enzyme
Regulation of oxidative stress, growth factor signaling, ion homeostasis.
Klotho deficiency
Trigger for aging
Stem cell senescence and depletion
Autophagy decreases
Oxidative stress
Insulin /IGF signaling increases
Maintenance of Klotho levels
Stimulation of endogenous klotho production
Administration of exogenous Klotho protein
Potential therapeutic target to retard aging and attenuate age- associated diseases
