Beall Study Guide Flashcards
What are the hallmarks of aging?
- Altered intercellular communication
- genomic instability- DNA repair activity correlates with longevity
- telomere attrition
- epigenetic alterations, loss of proteostasis
- deregulated nutrient sensing
- mitochondrial dysfunction
- cellular senescence
- stem cell exhaustion
What are the two forms of Alzheimers disease (a loss of proteostasis)?
Amyloid plaques (beta-amyloid peptide- extracellular) and neurofibrillary tangles (tau protein- intracellular) lead to brain shrinkage
What is the Hayflick limit (cellular senescence)?
describes the fact that somatic cells have a limited ability to replicate in culture
What are the two types of Alzheimers?
1) rare early onset familial form (fAD) - mutations
2) later sporadic form (sAD)
What is the cause of fAD Alzheimers?
mutations in amyloid precursor protein (APP) and presenilin 1 and 2 (PSEN 1, 2), gamma - secretase
What is the cause of sAD?
unknown, increase risk: apolipoprotein E allele
What do senescent cells secrete?
cytokines, growth factors and proteases
What type of drug can kill off senescent cells and renew the organ?
senlytics
What are telomeres and what role do they place in the Hayflick limit?
Telomeres: structures at ends of chromosomes
- telomere attrition causes Hayflick limit due to the lack of telomerase causing chromosomes to get shorter and shorter
What type of cells is telomerase active/inactive in?
active in germ cells and many tumors, turned off in somatic cells
What does telomerase contain?
RNA and proteins with reverse transcriptase, can be put into somatic cells to immortalize
What evidence found goes against the free radical theory?
anti-oxidants are essential (vits c and E) but don’t extend life
High frequency of mutations within the genome of a cellular lineage
genomic instability
- mutations can include changes in nucleic acid sequences, chromosomal rearrangements or aneuploidy
Telomere attrition
shortening of a telomere with each cell division, leading to aging of cell
What is the end replication problem?
due to lagging strands Okazaki fragments, not enough room to prime for last fragment, leads to consistent loss of DNA
cellular senescence
when cells age they secrete cytokines, growth factors and proteases
changes in chemical structure of DNA that do not result in alteration of DNA sequence
epigenetic alterations
unfolding of proteins which is detrimental due to loss of function
loss of proteostasis
- aggregation of these issues leads to aging (associated with Alzheimers)
deregulated nutrient sensing
insulin and IGF-1 and other signaling pathways relationship to dietary restriction and again
What do high levels of AMP activate?
AMPK
What do high levels of NAD+ activate?
SIRT1
Due to having own genome oxidations may occur that will lead to aging of cell overall
mitochondrial dysfunction
healthy cells constantly replenished by stem cells, when run out aging occurs
stem cell exhaustion
Process known as “inflammaging: falls into this category and leads to diseases such as atherosclerosis, diabetes, obesity, arthritis, periodontitis
altered intracellular communication
- infammaging: aged organisms have chronic state of inflammation
