5: neurobio of normal aging

Question 1

age related changes in immune system? cardiovascular? respiratory?

Answer 1

I: increased susceptibility to infection. C: increase in size/weight of heart, increased collagen in blood vessels. R: decreased vital activity

Question 2

age related changes in musculoskeletal system? GI? integument

Answer 2

reduction in muscle mass/strength. decreased blood flow to gut and liver, altered absportion from GI tract. graying of hear, wrinkling of skin

Question 3

age related changes in endocrine syste,?

Answer 3

levels of GH, LH, FSH, ACTH decrease = decreased IGF1, estrogen, testosterone, DHEA

Question 4

8 age related changes in the CNS

Answer 4

gross brain atrophy. ventricular enlargement. selective regional neuronal loss. selective deterioration of axons/dendrites. plauques and NFTs. regional decrease in NTs/neuromodulators. regional decline in cerebral blood flow + cerebral metabolic rate.

Question 5

3 lines of evidence that aging is governed by genetic factors

Answer 5

life span differences between different inbred strains of lab animals. life spans of human MZ twins similar to each other vs. DZ twins. identification of genes in fruit flies, worms, yeast that affect duration of life.

Question 6

gene for abolishing aging?

Answer 6

no specific gene so far has been identified which can abolish aging process

Question 7

aging genes in fruit fly/worms: increase life span by regulating (2)?

Answer 7

somatic maintenance + repair. longevity assurance.

Question 8

why do experiments in c elegans + d. melanogaster?

Answer 8

invertebrates: short, highly plastic life span. for example C elegans 3 week lifespan + 4 larval stages

Question 9

c elegans: what happens during adverse conditions

Answer 9

diverts from normal moults into long living dispersal form called the dauer larva. dauers show resistance to stress, survie about 6 months, then complete development on favorable conditions

Question 10

genes for transitioning into dauer state?

Answer 10

daf genes (dauer formation genes) daf-2, 12, 16, 18, 23. age-1 gene.

Question 11

mutations in daf2/23 or age-1 result in?

Answer 11

increase adult life span by turning on gene expression that transduces dauer features

Question 12

daf 2 encodes? age -1?

Answer 12

IGF-1 receptor. age 1 codes for mammalian homologue of phosphatidylinoistol 3 kinase, downstream enzyme of IGF1 pathway

Question 13

mutants which involve clk genes display?

Answer 13

extended lifespans

Question 14

longest live C.elegans have what mutations?

Answer 14

daf-2/clk-1 double mutants have a 5 fold increase in life-span

Question 15

what increases life span of d. melanogaster? what other genes involved?

Answer 15

insuling signaling pathway gene mutation. also: mth (Secretin like receptor). indy (homologous to krebs cycle intermediated). SOD and catalase (antioxidant pathways)

Question 16

humans: age related changes in gene expression apparent when?

Answer 16

middle age. more pronounced after 70 years

Question 17

brain specific microarray studies reveal?

Answer 17

age associated induction of stress response genes. significant reduction of mitochondrial genes.

Question 18

normal aging also associated with?

Answer 18

reduced transcription of genes involved with synaptic function + protein transport

Question 19

what % of genes expressed in brain are age -regulated? how do we know?

Answer 19

transcriptional profile of aging human frontal cortex: 4% of genes

Question 20

French centenarians study: what genes associated with human longevity?

Answer 20

APOE2. angiotensin converting enzyme ACE loci

Question 21

hereditable diseases and aging?

Answer 21

some display few but not all signs of normal aging = caused by mutation in genes.

Question 22

werner syndrome: what gene? encodes for? problems with mutations?

Answer 22

defect in WS gene, that encodes a DNA helicase RecQ that regulates genome stability. mutation impairs DNA replication, repair, resolving DNA sec. structures double strand break repair*

Question 23

dietary restriction and aging?

Answer 23

rodents, nematodes, spiders, fish: increases life span. in rodents by 50%. unclear about aging rate in humans

Question 24

how does dietary restriction increase longevity

Answer 24

protects cells against damage

Question 25

environmental enrichment and aging?

Answer 25

social housing, exercise wheels, toys, activity stimuli reduces effects of aging on plasticity and cognition

Question 26

human somatic tissues: aging marked by? what are they? do what?

Answer 26

loss of telomeres: TTAGGG repeats located at ends of DNA strands that maintain chromosomal integrity.

Question 27

telolmeres: shortening by? critical length?

Answer 27

gradual shortening by about 100 bp per cell division. when reach below critical length, cells stop dividing, undergo cellular senescence

Question 28

telomerase

Answer 28

enzyme, prevents shortening of chromosome by extending telomeric repeat sequences

Question 29

role of telomeres in cellular aging supported by?

Answer 29

cancer, immortalized cells have activated telomerase = they can divide indefinitely