week 6

Question 1

cellular senescence is ___________ state of cell cycle arrest where as quiescence is the _____________ cell cycle arrest

Answer 1

Senescence - irreversible (anti-tumor)

Quiescence - reversible (secrete mitogens)

Question 2

As you get older _________ proteins (TFs) associated with longevity decline with age and inhibited by insulin

Answer 2

FOXO

Question 3

What molecule inhibits FOXO, that normally activates genes involved in stress resistance? a nutrient sensitive pathway

Answer 3

Insulin

Question 4

Insulin is (anti or pro aging?)

Answer 4

PROaging - making aging worse

Question 5

FOXO is (anti or pro aging)?

Answer 5

ANTIaging - longevity

Question 6

TOR is (anti or pro aging?)

Answer 6

PROaging - stimulate aging processes

Question 7

AMP kinase pathway is (anti or pro aging?)

Answer 7

ANTIaging

Question 8

Sirtuins are (anti or pro aging?)

Answer 8

ANTIaging

Question 9

What genetic pathway that influences aging has NAD+ dependent lysine deacetylases that regulate metabolism, genome stability and other processes?

Answer 9

Sirtuins

Question 10

Telomere shortening is implicated in cellular senescence but CAUSES _________ senescence; the arrest of primary cell cultures after a few rounds of divisions inducing growth arrest and then into crisis.

Answer 10

replicative senescence

Question 11

Replicative senescence of human cells can be reduced by the addition of what enzyme?

Answer 11

Telomerase - extends telomere

Question 12

What component can damage membrane components that is caused by respiration, immune cells, ionizing radiation and hypoxic environments?

Answer 12

ROS

Question 13

What molecules can quench free radicals, iron, and peroxide?

Answer 13

Anti-oxidants

Question 14

Vitamin C (can take as much as you want), E and A (carotenoids) (cannot take as much), melatonin and fish oil are all what?

Answer 14

Anti-oxidants

Question 15

What is described by mutations in mtDNA leading to a decline in electron transport machinery with an increase in ROS which in turn Increases ROS which cycles back to further damage mtDNA?

Answer 15

the mitochondrial free radical theory of aging (MFRTA)

Question 16

What does this hypothesis explain in regards to contributing to aging?

• defect in proof reading polymerase gamma
• dominant negative mutation in Twinkie – a mtDNA helicase
• mtDNA mutation in embryogenesis limiting stem cells life

Answer 16

Mitochondrial mutations and the stem cell hypothesis:

Question 17

Why do older cells have shorter telomeres?

Answer 17

Because DNA polymerase requires a free 3’ OH, the ends of each chromosome are shortened at each round of DNA replication

Question 18

______ is a Serine threonine kinase that promotes aging by adding phosphate groups to target proteins

Answer 18

TOR

Question 19

What are genetic disorders that result in the premature appearance (signs/symptoms) of aging?

Answer 19

Progeroid syndromes

Question 20

What type of progeroid syndrome only affects one tissue type and what are two examples?

Answer 20

unimodal - Alzheimers and parkinsons

Question 21

What type of progeroid syndrome only affects one tissue type and what are two examples?

Answer 21

unimodal - Alzheimers and parkinsons

Question 22

What progeroid syndromes affect subsets of tissues that are involved in normal aging?

Answer 22

Segmental progeroid syndromes

Question 23

What two syndromes are caused by mutated NER genes and are part of the TGIIH complex that is involved both in general DNA repair and in transcription coupled DNA repair

Answer 23

• Xeroderma pigmentosum
  
  • Cockayne syndrome

Question 24

What clinical benefits does caloric restriction on aging?

Lowers: ______ &_______

Increases: _____ & _______

Answer 24

Lowers: insulin (IGF) & amino acids

Increases: NAD+ & AMP

Question 25

A patient presents with progressive impaired coordination or voluntary movements, redish skin lesions and mucus membranes due to widening of blood vessels, impaired immune function and increased risk of developing neoplasms, what disease is this?

Answer 25

* _Ataxia telangiectasia_

Question 26

What mutation causes _Ataxia telangiectasia?_

Answer 26

ATM gene mutation

Question 27

A patient presents with alopecia, no subcutaneous fat, thin and tight skin, prominent veins on head and scalp, protruding lips and small jaw. No intellectual disabilities and normal cause of death is myocardial infarction or stroke between the ages of 7-20 years, what disease is this?

Answer 27

_Hutchinson-Gilford progeria syndrome_

Question 28

Hutchinson-Gilford progeria syndrome is from a mutation in what gene and what mode of inheritance of this disease ?

Answer 28

LMNA gene autosomal dominant

Question 29

A patient in their 20s presents loss of hair, graying, cataracts, diabetes osteoporosis, and is thought to have an increase in risk for certain cancers. What disease is consistent with this presentation?

Answer 29

* _Werner syndrome_ *

Question 30

_A defect in what gene that encodes a helices is mutated in Werner syndrome? What does this cause?_

Answer 30

RECQL gene (WRN) shortening of telomeres with defective DNA repair

Question 31

A patient presents with short stature, mild facial erythema, increased risk for COPD, diabetes and malignancies (not a true premature aging syndrome). What condition is responsible?

Answer 31

Bloom syndrome

Question 32

Bloom syndrome is caused by a mutation in what gene that codes for a helices?

Answer 32

RECQL genes (BLM)

Question 33

Patient presents with photosensitivity, growth failure, hearing loss, leukodystrophies and ventricular atrophy from dilation causing neuronal aging (type I and II). What condition is this and is caused by a defect in what?

Answer 33

* _Cockayne syndrome_ * _NER gene_

Question 34

Cockayne syndrome is caused by a mutation in what 2 specific NER repair genes?

Answer 34

ERCC6 and ERCC8

Question 35

Patient presents with premature aging of the skin, many freckles and cannot be exposed to uv light due to defect in NER. What condition is this ?

Answer 35

* _Xeroderma pigmentosum_

Question 36

Xeroderma pigmentosum is cause by what 3 NER gene mutations?

Answer 36

EPC, ERCC2 and POHL