Flashcards in 5: neurobio of normal aging Deck (29):
age related changes in immune system? cardiovascular? respiratory?
I: increased susceptibility to infection. C: increase in size/weight of heart, increased collagen in blood vessels. R: decreased vital activity
age related changes in musculoskeletal system? GI? integument
reduction in muscle mass/strength. decreased blood flow to gut and liver, altered absportion from GI tract. graying of hear, wrinkling of skin
age related changes in endocrine syste,?
levels of GH, LH, FSH, ACTH decrease = decreased IGF1, estrogen, testosterone, DHEA
8 age related changes in the CNS
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.
3 lines of evidence that aging is governed by genetic factors
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.
gene for abolishing aging?
no specific gene so far has been identified which can abolish aging process
aging genes in fruit fly/worms: increase life span by regulating (2)?
somatic maintenance + repair. longevity assurance.
why do experiments in c elegans + d. melanogaster?
invertebrates: short, highly plastic life span. for example C elegans 3 week lifespan + 4 larval stages
c elegans: what happens during adverse conditions
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
genes for transitioning into dauer state?
daf genes (dauer formation genes) daf-2, 12, 16, 18, 23. age-1 gene.
mutations in daf2/23 or age-1 result in?
increase adult life span by turning on gene expression that transduces dauer features
daf 2 encodes? age -1?
IGF-1 receptor. age 1 codes for mammalian homologue of phosphatidylinoistol 3 kinase, downstream enzyme of IGF1 pathway
mutants which involve clk genes display?
longest live C.elegans have what mutations?
daf-2/clk-1 double mutants have a 5 fold increase in life-span
what increases life span of d. melanogaster? what other genes involved?
insuling signaling pathway gene mutation. also: mth (Secretin like receptor). indy (homologous to krebs cycle intermediated). SOD and catalase (antioxidant pathways)
humans: age related changes in gene expression apparent when?
middle age. more pronounced after 70 years
brain specific microarray studies reveal?
age associated induction of stress response genes. significant reduction of mitochondrial genes.
normal aging also associated with?
reduced transcription of genes involved with synaptic function + protein transport
what % of genes expressed in brain are age -regulated? how do we know?
transcriptional profile of aging human frontal cortex: 4% of genes
French centenarians study: what genes associated with human longevity?
APOE2. angiotensin converting enzyme ACE loci
hereditable diseases and aging?
some display few but not all signs of normal aging = caused by mutation in genes.
werner syndrome: what gene? encodes for? problems with mutations?
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*
dietary restriction and aging?
rodents, nematodes, spiders, fish: increases life span. in rodents by 50%. unclear about aging rate in humans
how does dietary restriction increase longevity
protects cells against damage
environmental enrichment and aging?
social housing, exercise wheels, toys, activity stimuli reduces effects of aging on plasticity and cognition
human somatic tissues: aging marked by? what are they? do what?
loss of telomeres: TTAGGG repeats located at ends of DNA strands that maintain chromosomal integrity.
telolmeres: shortening by? critical length?
gradual shortening by about 100 bp per cell division. when reach below critical length, cells stop dividing, undergo cellular senescence
enzyme, prevents shortening of chromosome by extending telomeric repeat sequences