Model Systems III Flashcards
age-1
first described longevity gene
fertility and lifespan
a tradeoff as depicted by mutation in age-1
dauer larvae
live at least 7x longer
what do dauer larvae form in response to
high population density, high temperature, low food
daf-c
constitutively dauer
daf-d
can never enter dauer
(lf) allele
loss of function
(rf) allele
reduction of function
(gf) allele
gain of function
daf-2 mutants are conditional, meaning…
mutant at one temperature, wild-type at another
permissive temperature
folded protein
daf-2 promotes
dauer exit
a daf-2 mutant is
always a dauer
daf-2 also
encodes an insulin/IGF-like receptor
daf-16 promotes
dauer entry
daf-16 class
daf-d
phenotype that wins in epistasis test is…
the downstream gene
FOXO on
longevity
FOXO off
shorter lifespan
age-1 is activated by
daf-2 signaling
age-1; daf-16
does not live long
if genes are in the same pathway
always same longevity outcome
if genes are in parallel pathway
when you hit a gene in each pathway, outcome is additive
age-1 and daf-2
act in same pathway
daf-2 is like
insulin receptor
age-1 is like
PI3 kinase
daf-16 is like
FOXO
high signaling, pathway on
daf-16 activity off
down regulation of daf-2 insulin pathway
causes no phosphorylation of DAF-16, so it can translocate into the nucleus to promote transcription
daf-16 (insulin) target genes
stress resistance, antioxidant, protein folding
human homologs
c. elegan lifespan genes
in drosophilia, mutation of daf-2
increased mean lifespan of females
insulin/IGF signaling public or private?
public
FIRKO in mouse
extended longevity in mice lacking the insulin
receptor only in adipose tissue
decrease in GH, decrease in insulin
results in longevity
IGF-1
in adults tissue growth, cell division and cell survival
IGF-2
primarily fetal - growth
insulin
metabolism by promoting glucose uptake
high levels of insulin like signaling
promotes growth, reproduction
low levels of insulin like signaling
promotes maintenance, stress resistance (dauer)
target of rapamycin
TOR
down regulation of TOR
extends longevity
regulates eukaryotic growth and cell division
TOR
is TOR conserved
yes
TORC1 inhibited by
rapamycin
mTORC1 complex
contains Raptor and PRAS40
mTORC2 complex
contains Rictor, mSin1, and Protor-1/2
downside of rapamycin
immunosuppressant