MCM Final - Oxidation and the Cell Biology of Aging

Question 0

Damaged-Based Theory of Aging

Answer 0

aging result of continuous process of damage accumulation

Question 1

Programmed Theory

Answer 1

aging is result of genetically regulated processes

Question 2

two barriers to immortality hypothesis

Answer 2

progressive telomere shortening

gradual accumulation of damage

Question 3

Free Radical Theory of Aging

Answer 3

increase in free radical production with age produces increased cell damage

Question 4

superoxide

Answer 4

O2-

Question 5

hydrogen peroxide

Answer 5

H2O2

Question 6

hydroxyl radical

Answer 6

OH-

Question 7

mitochondrial superoxide dismutase (mSOD)

Answer 7

converts O2- (superoxide) to H2O2 in mitochondria

Question 8

mitochondrial nitric oxide synthase (mNOS)

Answer 8

always on

produces NO

NO and O2- react to produce another free radical (ONOO-)

Question 9

peroxynitrite

Answer 9

ONOO-

Question 10

mitochondrial DNA lacks what?

Answer 10

excision and recombination repair mechanisms

histones or DNA binding proteins

may be why oxidative damage to mito DNA increases with age

Question 11

Phagocytes

Answer 11

attack pathogens using a mix of oxidants

1 H2O2, NO, and O2- (respiratory burst)
2 MPO enzyme - utilizes H2O2 to create halide oxidants
HOCl and Cl2 (chlorine gas)
-potent antimicrobials

Question 12

respiratory burst

Answer 12

H2O2, NO, O2-

-produced by phagocytes to attack pathogens

Question 13

MPO Enzyme

Answer 13

create halide oxidants in phagocytes to kill microbes

Question 14

Heavy Metals source of oxidatants?

Answer 14

iron and copper

-fenton reaction

Question 15

caloric restriction

Answer 15

in rodents, restricting caloric intake by 30-60% can increase lifespan up to 40%

can begin into middle age and still increase lifespan

Question 16

why caloric intake relates to longevity?

Answer 16

reduced food intake means less oxygen utilization in mitochondria

decreased generation of O2-

Question 17

exercise and oxidative stress?

Answer 17

acute exercise - results in more oxidative stress

chronic exercise - increased oxidative stress results in long term up-regulation of endogenous antioxidant enzymes

Question 18

antioxidants

Answer 18

remove O2
scavenge ROS
inhibit ROS formation by binding metal ions

Question 19

exogenous antioxidants

Answer 19

natural

- enzymatic
- non-enzymatic (directly scavenging or indirectly chelating agent)

synthetic

Question 20

endogenous antioxidants

Answer 20

SOD, glutathione, Cat

Question 21

Glycation

Answer 21

modification of proteins by sugars

- well recognized marker of aging
- largely in ECM

results in cross linking of proteins and insoluble deposits

Question 22

malliard reaction

Answer 22

monosaccharides reach with N-terminal amino groups or arginine/lysine side chains
-forms a reversible product

oxidation of product by oxyradicals, catalyzed by metal ions
-forms an irreversible product

Question 23

RAGE

Answer 23

receptor for advanced glycation end products

on phagocytes, endothelial cells, and smooth muscle cells

- recruit phagocytes to area and induce inflammation
	- causing an increase in oxidative stress

Question 24

telomeres

Answer 24

protect end of linear DNA from degradation -highly repetitive and clusters of guanine residues 3' overhang binds into DNA strand (t-loop)

Question 25

hTERT

Answer 25

human telomerase reverse transcriptase -catalytic subunit of telomerase not expressed in senescent cells -can be upregulated

Question 26

hTERC

Answer 26

human telomerase RNA component constitutively expresed subunit of telomerase

Question 27

replicometer

Answer 27

telomere length directly related to the number of times it could divide

Question 28

capping

Answer 28

proliferating cells, regardless of length of telomere, have capped telomers senescent, regardless of length, have uncapped ends thought that uncapped telomeres are recognized as double strand breaks