The Biology of Ageing Flashcards
Explain the WHO classifications of oldness!
Young old: 60-74
Old old: 75-84
Oldest old: 85+
Centenarians: 100+
Average life expectancy?
in 2008 was 80 but every decade it increase by 1-2 years.
When do age related changes in the body appear? Do all the changes happen at the same rate?
Many from the 4th decade - but some as early as 10 years (hearing loss).
No, different effects in different cells.
Speed of neurones decreases but slower than decrease in respiratory function.
Senescence?
Gradual decline in body function, decreasing ability to survive stress (physiological) and maintain homoeostasis, increasing the probability of death.
What are the 2 theories of ageing?
1) Programmed ageing - genes turn on ageing.
2) Random ageing - accumulation of wear and tear.
What is programmed ageing?
A built in programme in the genome, activated at a certain stage in the organisms life cycle, leads to death via a self destruct mechanism.
What is the evidence for programmed ageing?
1) Species - different species have different lifespans.
2) Fast ageing syndromes:
- progeria; a collection of symptoms related to ageing.
- Wener’s; a single gene mutation…limited potential of cells to divide. ‘Cellular clock’.
3) Limited cell division - Hayflick’s limit - cells can only divide a certain amount of times.
Why are senescent cells a problem?
- Morphological strength - reduced!
- Secrete pro-oncotic factors
- Secrete proteases to degrade tissues - break connections between cells, cancer cells can migrate faster.
- Lack of cell division; reduced tissue/wound repair.
Telomeres and cell senescence?
End regions of chromosomes (telomeres) are lost with each division.
Due to the ‘end replication problem’ where during cell division, DNA polymerase can’t make new DNA to the very end of the chromosome.
BUT - telomerase enzyme…adds telomeres back onto DNA to counteract telomere shortening and increase the number of times a cell can divide.
But perhaps loss of telomeres is a protection against cancer?
Consequences of telomere shortening or damage?
1) Senescence arrest - ageing (osteoarthritis, osteoporosis, atherosclerosis, renal failure, skin ulcers).
2) Apoptosis
3) Attempt to repair - genetic instability, CANCER - 80-90% of all cancers show teolmerase re-expression.
Common features of genes for longevity?
There are no genes that are switched on for ageing but genes become deficient in maintenance.
- Progeria: gene mutation (helicase), involved in DNA maintenance and protein synthesis.
- Hayflick limit - telomerase repairs DNA after replication, but is absent in mature somatic cells.
~70% of genome is involved in maintenance and repair - therefore the number of genes influencing ageing may be large!
What is the random ageing theory?
Accumulation of wear and tear.
a) Oxygen - oxidative stress (oxygen free radicals)
b) Glucose - protein damage by reducing sugars (glycosylation).
What is the oxidative stress theory?
Cell damage is caused by reactive oxygen species (ROS) - including free radicals - molecules with an unpaired electron = unstable, give e- to nearby molecules and disrupt structure.
DNA is very susceptible!
Give some examples of reactive oxygen species.
Superoxide radical (O2dot) Hydroxyl radical (OHdot) Nitric oxide (NOdot) Nitrogen dioxide (NO2dot) Hydrogen peroxide Hypochlorite
Where do ROS come from?
Environment, lifestyle, pollution, diet (PUFA), infection, cell metabolism (mitochondria).
Explain the role the mitochondria plays in oxidative stress.
20-5000 per cell.
Electron transfer chain.
Escaped electron and O2 = superoxide
1-3% of the O2 in the ETC becomes an O2 free radical = 17 tonnes of free radicals in 70 years!
Oxidative stress causes mitochondrial dysfunction. Decrease ATP, increase ROS.
Damaged mitochondira can trigger cell death - apoptosis or necrosis (cell disintegration).
Protein damage?
Oxidised proteins - damaged by ROSE - increase as you age.
Correlate to decline in memoery - if you treat with something that neutralises free radicals - reduces protein oxidation and restores gerbil’s memory!
Excess O2?
Hyperoxia - encourages free radicals to be made.
ROS increases damage to telomeres - cells divide fewer times.
DNA oxidation?
Nuclear DA - 10,000 hits per day
Mt DNA ~, hits per day
Consequences -
…altered bases (mutations)
…strand break (cell senescence)
Give some examples of reactive oxygen species.
Superoxide radical (O2dot) Hydroxyl radical (OHdot) Nitric oxide (NOdot) Nitrogen dioxide (NO2dot) Hydrogen peroxide Hypochlorite
Where do ROS come from?
Environment, lifestyle, pollution, diet (PUFA), infection, cell metabolism (mitochondria).
Explain the role the mitochondria plays in oxidative stress.
20-5000 per cell.
Electron transfer chain.
Escaped electron and O2 = superoxide
1-3% of the O2 in the ETC becomes an O2 free radical = 17 tonnes of free radicals in 70 years!
Oxidative stress causes mitochondrial dysfunction. Decrease ATP, increase ROS.
Damaged mitochondira can trigger cell death - apoptosis or necrosis (cell disintegration).
Protein damage?
Oxidised proteins - damaged by ROSE - increase as you age.
Correlate to decline in memoery - if you treat with something that neutralises free radicals - reduces protein oxidation and restores gerbil’s memory!
Excess O2?
Hyperoxia - encourages free radicals to be made.
ROS increases damage to telomeres - cells divide fewer times.
