Beall Study Guide

Question 1

What are the hallmarks of aging?

Answer 1

1. Altered intercellular communication
2. genomic instability- DNA repair activity correlates with longevity
3. telomere attrition
4. epigenetic alterations, loss of proteostasis
5. deregulated nutrient sensing
6. mitochondrial dysfunction
7. cellular senescence
8. stem cell exhaustion

Question 2

What are the two forms of Alzheimers disease (a loss of proteostasis)?

Answer 2

Amyloid plaques (beta-amyloid peptide- extracellular) and neurofibrillary tangles (tau protein- intracellular)
lead to brain shrinkage

Question 3

What is the Hayflick limit (cellular senescence)?

Answer 3

describes the fact that somatic cells have a limited ability to replicate in culture

Question 4

What are the two types of Alzheimers?

Answer 4

1) rare early onset familial form (fAD) - mutations

2) later sporadic form (sAD)

Question 5

What is the cause of fAD Alzheimers?

Answer 5

mutations in amyloid precursor protein (APP) and presenilin 1 and 2 (PSEN 1, 2), gamma - secretase

Question 6

What is the cause of sAD?

Answer 6

unknown, increase risk: apolipoprotein E allele

Question 7

What do senescent cells secrete?

Answer 7

cytokines, growth factors and proteases

Question 8

What type of drug can kill off senescent cells and renew the organ?

Answer 8

senlytics

Question 9

What are telomeres and what role do they place in the Hayflick limit?

Answer 9

Telomeres: structures at ends of chromosomes

- telomere attrition causes Hayflick limit due to the lack of telomerase causing chromosomes to get shorter and shorter

Question 10

What type of cells is telomerase active/inactive in?

Answer 10

active in germ cells and many tumors, turned off in somatic cells

Question 11

What does telomerase contain?

Answer 11

RNA and proteins with reverse transcriptase, can be put into somatic cells to immortalize

Question 12

What evidence found goes against the free radical theory?

Answer 12

anti-oxidants are essential (vits c and E) but don’t extend life

Question 13

High frequency of mutations within the genome of a cellular lineage

Answer 13

genomic instability

- mutations can include changes in nucleic acid sequences, chromosomal rearrangements or aneuploidy

Question 14

Telomere attrition

Answer 14

shortening of a telomere with each cell division, leading to aging of cell

Question 15

What is the end replication problem?

Answer 15

due to lagging strands Okazaki fragments, not enough room to prime for last fragment, leads to consistent loss of DNA

Question 16

cellular senescence

Answer 16

when cells age they secrete cytokines, growth factors and proteases

Question 17

changes in chemical structure of DNA that do not result in alteration of DNA sequence

Answer 17

epigenetic alterations

Question 18

unfolding of proteins which is detrimental due to loss of function

Answer 18

loss of proteostasis

- aggregation of these issues leads to aging (associated with Alzheimers)

Question 19

deregulated nutrient sensing

Answer 19

insulin and IGF-1 and other signaling pathways relationship to dietary restriction and again

Question 20

What do high levels of AMP activate?

Answer 20

AMPK

Question 21

What do high levels of NAD+ activate?

Answer 21

SIRT1

Question 22

Due to having own genome oxidations may occur that will lead to aging of cell overall

Answer 22

mitochondrial dysfunction

Question 23

healthy cells constantly replenished by stem cells, when run out aging occurs

Answer 23

stem cell exhaustion

Question 24

Process known as “inflammaging: falls into this category and leads to diseases such as atherosclerosis, diabetes, obesity, arthritis, periodontitis

Answer 24

altered intracellular communication

- infammaging: aged organisms have chronic state of inflammation