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 DNA
2. 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 perturbation
5. hyperoxia (cellular stress)

Question 5

name three ways the body counteracts senescence

Answer 5

1. decreased production of IGF1 and decreased TOR signalling
2. caloric restriction stimulates increased activity of DNA repair mechanisms
3. 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