0520 - Ageing/Cell senescence - PZ Flashcards
what’s the difference between ageing and senescence?
ageing is the gradual changes in structure of organism with time, not associated with disease.senescence is the process of growing old, resulting from accumulation of deleterious ageing process
what non public health measures extends lifespan?
Lowering ambient temperature (poikilotherms)Reducing physical activity (housefly)Dietary restriction (rodents)Metabolic rate (debated)However, these are mostly theories, there isn’t definitely proof.
what is Hutchinson-Gilford Syndrome
an autosomal recessive disorder where aging commences in childhood
what is Werner’s Syndrome
Werner’s Syndrome – Autosomal recessive disease. DNA helicase abnormality (DNA replication and repair) leads to with chromosome instability and higher rates of gene mutation
what is the role of telomere and telomerase in cell senescence?
each time a cell replicates and DNA unwinds, chromosomes loses a bit of it’s telomere.in somatic cells where there is no telomerase activity, p53 gets activated and vegetates/kills the cell.
what is a telomere, where is it located.
Telomeres are unique tandem repeat structures (TTAGGG X 1000), located at end of chromosomes. (like the plastic thing on your shoelace)
what is the role of telomerase?
synthesises new telomere. very few in somatic cells, mostly in germline cells, and tumour cells.
what evidence do we have for the telomere theory of cell death
Population studies (using blood leucocytes) have shown average shorter telomere length in families with familial high rate of Cardio-vascular disease.
in addition to germline cells, where else would you expect to find high telomerase activity?
in cancerous cells. the presence of telomerase mean that these cells can undergo indefinite amount of cell divisions.
what are the 3 biological factors thought to be implicated in cell senescence?
DNA repair problems - cumulation of random error leading to altered proteins. However, this is not necessarily causative as problems arise because these proteins are not being cleared.Protein modification - qualitative changes in proteins.Free radical damage (Mitochondrial DNA) - refers more to mitochondrial diseases.
what is mTOR, how is it implicated in ageing and cell death?
mechanistic target of rapamycin - regulates cell growth and metabolism.removal of mTOR in non-mammals significantly increased age, and a number of human diseases are also caused by altered mTOR.
what do senescence look like? (histology morphology)
nuclei = irregular and lobulated.mitochondria = pleiomorphic and vacuolated.ER = decrease in amount and complexity.Golgi = distortedCells also accumulate more pigments due to lipid peroxidation and membrane degradation
what are some consequences of ageing?
white hair, as melanocytes don’t migrate and tyrosinase activity drops.macular degeneration, due to high free radical production in retina and lipofuscin deposits which stops mitochondrial respiration but generates free radicals at the same time.reduced fertility
