8: epigenetics in aging Flashcards
what is programmed longevity?
ageing as the result of sequential switching on and off of certain genes, with senescence being defined as the combination of processes of deterioration which follow the period of development of an organism
what is senescence?
process by which a cell loses its ability to divide, grow and function, which eventually leads to death
- senescence proteins are secreted -> causes neighbouring cells to also become senescent
what is senescence?
process by which a cell loses its ability to divide, grow and function, which eventually leads to death
- senescence proteins are secreted -> causes neighbouring cells to also become senescent
what is HP1?
a protein recruited by HIRA which leads to formation of senescence associated heterochromatin
what are primary hallmarks of ageing?
causes of the damage
what are the types of epigenetic alterations in aging?
DNA methylation (global hypomethylation, local hypermethylation)
histone modifications (hypermethylation/acetylation, hypomethylation)
chromatin remodelling (eu/heterochromatin formation)
generally, how does an altering histone modifications lead to aging?
transcriptional drift -> chromosomal/cell instability -> tissue function deteriorates
how does LINE/SINE affect aging?
de/hypomethylation of LINE/SINEs lead to expression of these transposable elements -> genes are shifted to another place -> alters normal gene expression -> genomic stability affected
what is the diff between biological and chronological age?
biological age is determined by status of tissues and cells
chronological age is your age by year
what if bio < chronological age and vice versa?
bio < chr age: healthy ageing
chr < bio age: premature ageing
what are some ways biological age is predicted?
epigenetic clock (best indicator - a single test, good hazard ratio)
telomere length (old method)
metabolic age score (eg BMI)
composite biomarker (eg blood tests)
what is hazard ratio?
relative risk of the event
measures an individual over time to show how accurate the biological clock method is
lower ratio -> less good of a bio age indicator
what is an epigenetic clock?
a biological clock to measure the age of most human tissues, cell types, and organs in the same individual, which can help in predicting the ageing process (age acceleration)
what is age acceleration like over a lifespan?
age acceleration decreases as age increases
what are the 3 epigenetic clocks and how many predictive sites are there?
Hannum’s clock (71CpGs)
Horvath’s clock (353 CpGs)
Levine’s clock (DNAm PhenoAge) (513 CpGs)
