Intro - ageing

Question 1

What does ageing depend on?

Answer 1

Genetic and environmental factors (interact)
Genetic - in-built clonal senescence
Environmental - replication and wear and tear (i.e. normal loss of cells during life and also sublethal damage eventually leading to organ failure - reason CVS and CNS failure is common as they’re less able to regenerate)
i.e. some features of ageing are inevitable and other are based on lifestyle

Question 2

What is a telomere?

Answer 2

Non coding, randomly repetitive DNA sequence at the ends of the chromosomes.

They allow replication of DNA so the cells can divide.

Question 3

What is the Hayflick limit?

Answer 3

A limit of the number of divisions a cell can do - due to the fact that telomeres shorten every time the cell divides so they eventually become too short for the DNA polymerase to engage with.

Question 4

Why do the telomeres shorten with repeated cell divisions?

Answer 4

Prior to mitosis, DNA is replicated. But the telomere sequences are not fully copied during this.
Only in germ cells/embryos are the telomeres replicated by telomerase

Question 5

How is telomere length inherited?

Answer 5

Paternally (we think) and is associated with parental lifespan

Question 6

What is thought to decrease cell aging?

Answer 6

Calorie restriction by reducing the amount of telomere shortening

Question 7

What can cause damage to cells (and therefore wear out cells that cannot divide e.g. neurones)

Answer 7

Mutations in DNA
Crosslinking of proteins
Loss of Ca influx controls (too much comes in)
Damage to mitochondrial DNA
Loss of DNA repair mechanism
Free radicals
Telomere shortening
Accumulation of toxic by products of metabolism

Question 8

What happens during ageing?

Answer 8

• Dermal elastosis
  (causes wrinkles. UV-B light causes cross-linking of collagen so it’s not elastic anymore)
• Osteoporosis
  (decrease in normal bone matrix, increased resorption and decreased formation (lack of oestrogen))
• Cataracts
  (UV-B light crosslinks proteins so they’re opaque)
• Senile dementia
  (atrophy of brain as nerve cells cannot be replaced)
• Sarcopenia
  (loss of muscle due to decreased growth hormone, testosterone and increased cytokines)
• Deafness
  (hair cells in ear are not replaceable)
• Impaired immunity
  (less production of T cells)
• CVS lesions
  (e.g. fatty streaks progressing and decreased elasticity of arteries with age so increased BP)