ageing Flashcards
what are progeria syndromes?
genetic diseases leading to premature ageing
list some progeria syndromes
- elhers danos
- werner
- hutchinson guilford
- cockayne
- nester guillermo
DEFINE: senescence
age related decline in vital physiological functions
how does unrepaired DNA damage lead to ageing
- activates PARP
- PARP uses NAD in a reaction
NAD depletion leads to senescent cells
how does a senescent cell drive ageing?
- secretes pro-inflammatory mediators
* sits in stem cell niche and blocks stem cell mediated repair
how may ROS extend life span?
- hormesis - low level of insult activates huge protective mechanisms
- protective superoxide induced pathway - alarm pathway activating protective responses. does not directly damage cells.
how does the IGF pathway affect ageing? describe the pathway
- insulin binds to daf2
- activates age-1 pathway (PI3K)
- inhibits FOXO, SKN1 & HSF1
FOXO regulates antioxidant genes -> increases resistance against ROS
IGF pathway decreases lifespan
how does insulin activate the TOR pathway?
insulin inactivates tsc1/tsc2 via PI3K pathway
tsc1/tsc2 inactivates TOR
how does the TOR pathway affect ageing?
decreases lifespan
what is rapamycin
inhibitor of TOR pathway
increases lifespan
what are the downstream target genes of the TOR pathway?
activates S6-kinase
represses 4E-BP = stimulates autophagy
what are sirtuins?
NAD+ dependent protein deacetylases
how do sirtuins increase lifespan?
- activates FOXO
- activates mitochondrial unfolded protein response
- NAD+ is an essential cofactor for sirtuins
what activates sirtuins?
resveratrol
how do signals from the gonads affect lifespan?
longevity signals from somatic gonad are inhibited by germ cells
