theories of ageing Flashcards
theories
proximate theories- how we age, often cell level, mechanisms of ageing
ultimate theories- why we age, evolutionary level
damage accumalation theories
propose that ageing involves greater exposiure to stressors and accumalation of damage
glycation- binding of sugar molecule to protein which may form advances glycation end products (AGE) cross linking adjacent protein (eg collagen) molecules- caused by high sugar levels in the blood
accumalation of amyloid plaques in alzeihmers disease
collagen cross linking
collagen fibril becomes corss linked
collagen fibre then collagen bundle
bundles of collagen can cause stiffening of tissues
somatic mutation accumalation
damage to dna
soma- all body cells except germ cells
stressors- hyper/hypo oxia, reactive oxygen species (ROS), ionising/ ultraviolet radiation
may induce dna damage eg DSB - inititates dna damage response
dna damage- tumor suppressor p53, halts cell cycle (reduces likelihood of cancer), activation of p38 mitogen activated protein kinase (MAPK) triggers mitochondrial dysfunction
can protect against cancer but can contrribute to apoptosis and impairment in cell function (cell senescence)
doesnt affect mutations in offspring as is not in germ cells
limited cell division
fully mitotic cells- continue replicating eg stem cells and germ cells, differentiated celsl eg fibroblasts, endothelial and intestinal cells
post mitotic cells- do not replicate in adults eg skeletal muscle, neurons and cardiac muscle
life history of cultured mitotic cells
phase 1- initial slow proliferation
phase 2- rapid proliferation
phase 3- declining proliferation
cellular senescence
immortilisation- indefinite proliferation
proliferation- rapid reproduction of cells
hayflick limit
hayflick cultured human fibroblasts, divide for finite periods- 50/60 divisions (HL)
hayflick limit differs between cell type, individuals and species
stressors can accelerate cellular senescence eg hyper/hypo oxia, reactive oxygen species (ROS), ionising/ultraviolet radiation
cellular senescence
cell division- lengthening of cell cycle
morphological- enlarged, multinucleated cells, breakdwon of extracellular matrix, changes in chromatin structure ]
cell function- decrease in protein synthesis, decreased catabolism- accumalation of protein complexes eg lipofucsin
senescence associated secretory phenotype- SASP- increased secretion of pro inflammatory cytolines, matrix metalloproteinases, growth factors, may induce bystander effect in neighboruing cells
free radical/ reactive oxygen species
free radicals- charged particles containing unpaired electrons
produced during oxidative phosphorylation
highly reactive- damage molecules
superoxide produced in C1 and C3 of ETC- in presence of iron can turn into hydroxyl ion and these are highly reactive and cause oxidative damage to lipids, proteins and nucleic acids
harmful effects of ROS
in presence of Fe, h2o2 is converted to hydroxyl (‘OH) radical
‘OH reacts with polyunsaturated lipids in cell membrane, gunanine sugar bond in nucleic acids, proteins
beneficial effects of ROS
h2o2 involved in formation of disulfide bonds (important in protein structure)
superoxides damaging effects on lipids in cell membrane employed by macrophages on pathogens
increased expression of antoxidant enzymes
antioxidants
endogenous
enzymes that react with free radical superoxide dismutase (reduced superoxide to h2o2) + catalase (reduced h2o2 to form h2o)
increased defences may increase lifespan in nematodes
exogenous
molecules that are oxidised by free radical, hence neutralising it (eg vit e and c)
supplementation doesnt extend lifespan
ROS in ageing
production may be increased by changes in signalling pathways
can contribute to mitochondrial dysfunction
3 main theories of ageing
limited cell division
reactive oxygen species
damage accumalation
