15. ageing biology 1 Flashcards
how has the field of ageing research changed?
people were looking for genes that drive the ageing process and now we are looking for genes that keep our genome healthy and resilient
what two fields of biology are repeatedly linked?
cancer biology and ageing biology
what is the number of risk factor for developing cancer? and what is one reason for this?
ageing
out defence against cancer decreases with age
what is happening in Japan and why is this a problem?
there are lots of old people and the birth rate is declining - how will these old people be supported if there are not young people to work and pay taxes for social care
what is the grandmother hypothesis?
it was useful to societies health to have a few grandmothers around, with spare energy to look after children and with wisdom
what is seen after natural disaster that proves the grandmother hypothesis?
old people are wiped out and so it takes society longer to re-develop as society has lost its historical knowledge
therapeutics that target the ageing process are not necessarily trying to increase life span, what are they trying to achieve?
a more healthy ageing process
what might happen to stem cells as we age?
they may become less well controlled and become depleted
by 2025 how many people will be over the age of 60?
1.2 billion
people are living longer
how do we define ageing?
in terms of resilience
when you are young and healthy your cells, tissues and genomes have lots of protection mechanism, if a stressor comes we can resit it
when you get older this ability decreases
what happens when a old tissue is stressed?
it is less able to handle the stress and less able to regernate afterwards
name 5 diseases that are associated with ageing
- cardiovascular disease
- arthritis
- T2D
- pulmonary disease
- cancer
in terms of therapeutics, what do we need to be careful about when we observe changes in old peoples physiology?
these changes may not actually be harmful, it may just be part of the tissue keeping itself going longer, if we try and reverse this it may lead to problems
why is studying the ageing process difficult? (5)
- ageing is a gradual, dynamic process
- there is lots of heterogeneity
- there are external and internal influences on ageing
- their is a lack of biomarkers for ageing
- organs can age at different rates
what are being used more and more in the ageing biology field?
model animals like C elegans and Drosophila as humans and mice are expensive
when you pass the age of 50 what starts to happen to your skeletal muscle? (5) and what does this lead to?
- loss of 1-2% of muscle per year
- disorganisation
- increased fibre size variability
- protein aggregates
- increased infiltration of non-contractile material like fat and connective tissue
> this leads to reduced muscle strength and functional decline
what also have an effect on muscles in the ageing process?
decline in mitochondria number and function results in less energy available to muscle
what is observed about the appearance of mitochondria in old muscle tissue? (4)
- there are fewer mit
- they are larger
- vacuolization of the matrix
- shortened cristae
skeletal muscle may have a stress response that upregulates number of mitochondria, why may this still not be very good in old people? and what might also be observed?
- mitochondria generated might be less functional
- a decline in number of mitochondria might also be observed
what is autophagy and how what happens to this in the ageing processes? giving an example
autophagy is hen cells can engulf dis-functioning organelles, break them down and make them safe again
this becomes less efficient in the ageing process
an example of this is mitochondria autophagy as we don’t want them leaking ROS
how much does the ATP produced in muscles decline per decade?
by 5%
what happens to mtDNA in the ageing process?
it becomes more damaged, levels of 8-oxoguanine increase
what is 8-oxoguanine ?
a DNA lesion that results from ROS
it can lead to mismatch pairing with adenosine
what three things are seen increasingly oxidised in the mitochondrial ageing process?
DNA
lipids
proteins
old people might produce a sufficient basal level of ATP, how does this make stress and exercise? and what may happen as a result of this?
they may feel pain and breathlessness
they ae less likely to exercise and this makes them even more weak
what other four factors also affect skeletal muscle health?
- endocrine system
- neural system
- cardiovascular system
general health decline will have a knock on affect on skeletal muscle
why can circulatory system affect skeletal muscle?
it affects oxygen and nutrients availability
why is geriatric care complex?
when people age they may have several co-morbid conditions
changes in the muscle to fat ratio can lead to what?
- metabolic syndrome
a cluster of biochemical and physiological abnormalities which are associated with CV disease and T2D - and insulin resistance
what is insulin resistance and what can it lead to?
when the body does not respond to insulin as efficiently as it should, this can lead to type 2 diabetes
what type of cells can generate ROS and release fatty acid into the blood?
fat cells
fatty acids in the blood are known to cause what?
muscle insulin resistance by inhibiting insulin stimulated glucose uptake and glycogen synthesis
what is seen in almost all old tissue?
inflammation
name a post mitotic cells in skeletal muscle
adult myofibres
name the stem cells in skeletal muscle and name a marker for them
skeletal muscle cells
psx7
when stem cells in the skeletal muscle are stimulated to divide what do they do?
they fuse with damaged muscle fibres and regenerate myonuclei and locally regenerate tissue
what is seen about old satellite cells? and what two things might this be due to?
there are less of them and they divide less/come out of G0 less
- they divide and make the wrong lineages (more fibrotic and less myogenic)
>it might be due to changes in the niche or changes in the satellite cells genome
what is seen when old mice satellite cells at cultured in vitro?
- they produce less organised and more fragile myotubes
when satellite cells divide and make the wrong lineage, what affect does this have on tissue?
fibroblasts like cells wiggle into the tissue and disrupt the skeletal muscle structure
where are skeletal muscle cells found?
in contact with skeletal muscle fibre and basal lamina
define some contributing factors to the satellite cell niche (5)
- fat cells
- fibroblasts
- vasculature
- nerve cells
- muscle fibres
define some contributing factors to the ageing satellite cell niche (5)
- increase adipocytes
- thicker basal lamina and more ECM deposition which stiffen muscle
- decreased endothelial number
- impaired chemotaxis of macrophages
- increased fibroblasts
what happens to stem cell regulation in the ageing satellite cell niche?
there is less positive and more negative regulation of stem cells
factors that regulate stem cells are deregulated and so satellites do not know when to divide
what happens to the cross sectional area of myofibres as we age?
it is reduced
what is seen when old mice hind limb muscle is put into a young mouse? and what is seen when a young muscle is put into an old mouse?
old hind limb muscle into young hose can regenerate like a young muscle
young muscle in old host cant regenerate as normally would
this shows that intrinsic and extrinsic factors change as we age
what has parabiosis been shown to do?
- rejuvenate old satellite cells
- they also showed the involvement of carconical Wnt signalling in this process
describe Wnt signalling
when Wnt bids Frizzled receptor, APC and GSK3 are localised to the membrane, beta catenin is stabilised and can enter nucleus, bind TCF/LEF and promote gene expression and cell division
why might the results obtained from parasymbiosis experiments be hard to transfer into the clinic, and what may help overcome this?
if rejuvenation is due to Wnt signalling, it will be hard to influence this without increasing risk of cancer
this may be overcome by delivering treatment more locally