Aging

Question 1

Aging is characterized by an increased _________ to disease but it not a disease

Answer 1

vulnerability

Question 2

Aging is characterized by a decrease in the ______________

Answer 2

ability to maintain homeostasis

Question 3

lifespan between species

Answer 3

incidence of disease increases at a similar rate but the time scales are different between species, i.e. mice only live for 4 year, humans 100 but the rate of disease increases similarly

Question 4

what are issues that can contribute to aging related vulnerability

Answer 4

hormonal changes
loss of specific tissue architecture
decline in immune function

Question 5

what is senescence

Answer 5

cell cycle arrest

Question 6

what induces senescence

Answer 6

1. normal fibroblasts have a predetermined number of population doubling
2. telomere attrition
3. oncogen conversion
4. stress (o2)

Question 7

what is the hay flick limit

Answer 7

the lifespan of human cells is defined by the number off cell division a population undergoes
cell do not spontaneously immortalize

Question 8

what can drive immortalization in human cells

Answer 8

viral proteins

Question 9

what are the example of viral proteins that can escape senescence

Answer 9

SV40  T antigen 
-binds and inactivates p53 and Rb
Papilloma virus 
-E6-p53
-E7-Rb

Question 10

what is p53’s role in senescence

Answer 10

p53 is a tumor supressor, i.e. it stops cell growth. it is typically bound to mdm2 but when mdm2 is phosphorylated, p53 is released

Question 11

what are two targets of p53

Answer 11

p21-CDKi -> G1 arrest

PUMA-cytochrome c release -> apoptosis

Question 12

what is telomere attrition

Answer 12

the ends of telomeres shorten after each round of division, after many rounds, cells can undergo senescence

Question 13

what are the telomere binding protein

Answer 13

TRF1 and TRF2 bind to telomere repeats TTAGGG

Question 14

what is the T loop

Answer 14

t loop formation prevent DNA damage response by forming a loop. The 5’ overhang end loops back

Question 15

who has telomerase activity

Answer 15

mice, not humans

Question 16

what are the DNA repair protein involves in telomeres

Answer 16

KU70/80, ATM, DNAOK

Question 17

describe oncogene transformation

Answer 17

limited to immortal cells, and activated by introduction of Ras protein with a Valine 17 mutation

Question 18

what does Ras activate

Answer 18

“hyper-replication” causing activation of DNA damage response leading to senescence

Question 19

Senescence and chromatin remodeling

Answer 19

stress and DNA damage induce growth arrest
pRb bind to E2F target genes involved in S phase
laminB1 expression decreases

Question 20

what is the best marker for senescence

Answer 20

p16