Pathology Study Guide (Cellular Basis of Aging and Inflammation)

Question 1

what is senescence

Answer 1

the stage of cellular life cycle in which the cell becomes terminally non-dividing

Question 2

what’s the difference between senescence and G0 phase of cell cycle

Answer 2

cells in the G0 phase of the cell cycle do not divide, but they can enter the mitotic phase in response to physiologic stimuli while senescent cells cannot

Question 3

why is telomerase important

Answer 3

telomerase catalyzes the addition of protective bases to the DNA to prevent telomere shortening into coding DNA

Question 4

name and explain three mechanisms for cellular aging

Answer 4

1. accumulation of damage to mtDNA and nuclear DNA2. reduced replication (shortened in vitro life span and telomere shortening leading to DNA damage response)3. decreased protein homeostasis (reduced translation and activity of chaperones, proteases, and repair enzymes)4. chromatin perturbation5. hyperoxia (cellular stress)

Question 5

name three ways the body counteracts senescence

Answer 5

1. decreased production of IGF1 and decreased TOR signalling2. caloric restriction stimulates increased activity of DNA repair mechanisms3. increased sirtuin production (deacetylases that activate DNA repair)

Question 6

what is dyskeratosis congenita

Answer 6

depletion of hematopoetic stem cells due to telomere shortening; causes pancytopenia (low WBCs and RBCs), growth defects, bone defects, skin pigment defects

Question 7

what is Werner Syndrome

Answer 7

adult progeria (onset right after puberty) due to mutation of WRN (helicase protein); causes early senescence and accelerated aging

Question 8

Hutchinson-Gilford progeria syndrome

Answer 8

onset at birth; due to defect in lamin A (which fortifies nuclear envelope); causes DNA damage, chromatin disruption, induces stem cell differentiation (and thereby depletion),

Question 9

what are sirtuins?

Answer 9

deacetylases that silence DNA by allowing histones to wrap DNA much tighter

Question 10

what do lamins do

Answer 10

provide structure to the nucleus (especially important for mitosis) and regulate transcription

Question 11

what is hormesis

Answer 11

beneficial effects (stimulation of maintenance and repair) caused by the mild daily stress of caloric restriction

Question 12

how does inhibiting mTOR (via rapamycin for example) increase lifespan

Answer 12

decreases mitochondrial function => less ROS production,

Question 13

what is autophagy

Answer 13

process by which cellular components are recycled in order to provide energy and building blocks for the cell

Question 14

what happens to the amount of autophagy that occurs when an individual is older

Answer 14

the amount of autophagy declines

Question 15

which molecules, when released from necrotic cells, stimulate inflammation

Answer 15

uric acid, ATP, HMGB-1, DNA

Question 16

how does hypoxia induce cell injury

Answer 16

HIF-1alpha (hypoxia induced factor) is produced as a result of hypoxia and it is a transcription factor for inflammatory genes like VEGF (for vascular permeability)

Question 17

name the five clinical signs of inflammation

Answer 17

rubor (redness), calor (heat), tumor (swelling), dolor (pain) and loss of function

Question 18

what main vasodilators act to quickly widen the vessels in the seconds after the inflammatory response begins

Answer 18

histamine, nitric oxide

Question 19

what causes stasis of the blood in the acute inflammatory response

Answer 19

vasodilation and fluid loss due to increased permeability of the endothelial wall

Question 20

name the three main types of eicosanoids and what important precursor do they share?

Answer 20

prostaglandins, leukotrienes and lipoxins

they are derived from arachidonic acid

Question 21

which leukocyte predominates an acute injury/ infection in the first 6-24 hours and which predominates in the following 24-48hrs post-injury

Answer 21

neutrophils predominate first, then monocytes

Question 22

what three changes do platelets undergo after contact with collagen or vWF in the exposed ECM

Answer 22

1. change of shape and adhesion
2. secretion of granular contents (ADP, serotonin, etc.)
3. aggregation

Question 23

name 2 major COX inhibitors and explain what COX does

Answer 23

aspirin and indomethacin;

COX-1 and COX-2 promote synthesis of prostaglandins

Question 24

what are acute phase proteins and list a few

Answer 24

acute phase proteins are produced in the liver during the acute inflammatory response for release into the blood; they include C Reactive Protein, fibrinogen and serum amyloid A

Question 25

what do EGF and TGF-alpha do

Answer 25

they are mitogenic for epithelial cells, hepatocytes and fibroblasts

Question 26

what does HGF do

Answer 26

it is mitogenic for hepatocytes and epithelial cells (its receptor is c-Met)

Question 27

what does PGDF do

Answer 27

Platelet-Derived Growth Factor causes migration and proliferation of smooth muscle cells, monocytes and fibroblasts for wound healing

Question 28

what does VEGF do

Answer 28

Vascular Endothelial Growth Factor induces vasculogenesis (from existing vessels) and angiogenesis (new vessels), stimulates vascular permeability and activates t-PA

Question 29

is TGF-beta pro-inflammatory or anti-inflammatory

Answer 29

anti-inflammatory: it inhibits endothelial growth and promotes fibrous tissue formation, but also recruits neutrophils and macrophages

Question 30

what’s the difference between labile, stable and permanent cells

Answer 30

labile cells constantly have a high proliferation rate (GI, skin), stable cells have a generally low proliferation rate that can crank up when necessary (smooth muscle, endothelium), permanent cells can no longer divide (neurons, skeletal muscle and cardiac muscle)