BIO135 Senescence Notes.txt
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The telomere model of senescence is not as strong as ___.
Altering the insulin and insulin-like pathways results in ___.
- Increase in life span in C. elegans, Drosophila, and mice.
- Keeps mutant animals healthy with less age-related problems.
Effects of altering the insulin and insulin-like pathways are only detected in ___.
in the adult and not during developmental stages.
Animals with the mutant insulin pathway are generally ___.
The Daf-2 mutant was first discovered in ___.
Age-related genes in C. elegans include ___.
- Age-1 - Phosphoinositide-3-kinase (PI3K)
- Daf-2 - insulin receptor
- Daf-10 - forkhead transcription factor
Age-related genes in flies include ___.
- InR - Insulin receptor
- Chico - fruit fly receptor
Age-related genes in mice include ___.
IRS1 - insulin receptor substrate 1
In neurons, replacing ___ and ___ of ___ and ___ worms ___ wt age of the worms.
- age-1, daf-2
- age-1(-/-), daf-2(-/-)
Mutant with age-1(-/-) and daf-2(-/-) have lifespans that ___.
are twice as long.
In the metabolic model, in order to increase lifespan, ___.
- Insulin-signaling needs to be appropriate.
- Amount of insulin in resto of body (w.r.t. neurons) needs to lowered.
Metabolic rate appears to be ___ to lifespan possibly due to ___ and ___.
- inversely proportional.
- Exposure to oxidative stress.
- DNA damage
In fat tissue, ___ knockouts can ___ lifespan.
In flies, overexpressing ___ or ___ can also extend lifespan.
Data suggests that a ___ signal originating from fat tissue and the ___ pathway regulates longevity.
- Insulin/Insulin-like Signaling (IIS)
Why would pathway changes in fat tissue make a difference?
Related to cardiovascular disease
Germline ___ in worms extends lifespan.
Transplantation of ___ into older mice extends their lifespan.
In mice, mutants have lowered rates of ___, ___, and ___.
- cardiac problems
- Alzheimer's disease
There are relatively high numbers of gene variants coding for ___ in ___ species.
In vertebrates, there is/are ___ gene(s) coding for insulin, but ___ receptor variants.
What is the phenotype for IRS-4 knockout?
mild growth defect in males
What is the phenotype for IRS-2 knockout?
- short lifespan, diabetes (insulin resistance) in males.
- longer lifespan if brain-specific
What is the phenotype for IRS-1 knockout?
extended lifespan in females
Basic areas where lifespan extension mechanisms are unknown include ___ and ___.
- Downstream mechanisms (e.g. oxidative stress).
- Multi-gene effects.
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