Ageing

Question 1

What is ageing?

Answer 1

• progressive generalised impairment of function
• loss of adaptive responses to stress
• growing risk of age-related disease

Question 2

What are the 3 theories as to why we age?

Answer 2

• wear and tear
• adaptive evolution
• non-adaptive evolution

Question 3

What is the ‘wear and tear’ idea of ageing?

Answer 3

organism is a machine that wears out

inevitable price paid for complexity

caveat: not all animals age, e.g. those that have germ lines/stem cells to repair

Question 4

What is ‘adaptive evolutionary’ theory of ageing?

Answer 4

• selectively advantageous to species
• evolution and natural selection
• Darwinian principles
  caveat: ageing rarely seen in natural populations

Question 5

What is the ‘non-adaptive evolutionary’ theory of ageing?

Answer 5

• accumulation of mutations over time
• natural selection declines with age

caveat: no experimental support

Question 6

What is the role of ‘antagonist pleiotropic genes’ in ageing?

Answer 6

• early good effect therefore retained
• bad late effect contributing to ageing

evidence in drosophila

e. g. abnormal abdomen allele
- increased early function, reduced longevity over time

Question 7

What is the ‘disposable soma theory’ of ageing?

Answer 7

• development of non-adaptive evolutionary views
• organism transfers free energy into progeny
• success -> ensures survival of genes
• disposable = limited lifespan
• soma = not of germ line

rate of ageing PROPORTIONAL to investment in self-maintenance

e.g. programmed to survive not age

Question 8

How do we age?

4 categories

Answer 8

• system level theories
• cellular level theories
• genetic theories
• genomic stability

Question 9

What is the ‘neuroendocrine theory’ in ageing?

Answer 9

functional decrease in neurones and associated hormone (central to ageing process)

HPA axis controls growth and development and putatively ageing

decreased pulsatile GH and GnRH (ageing rats)

hormone replacement increases lifespan

Question 10

What is the ‘Hayflick phenomena’ in ageing?

Answer 10

fibroblasts have contact inhibition

more divisions if from a younger source/passage

biological clock

Hayflick limit is not usually reached in ageing organisms

may have important function in tumour regulation

Question 11

How do ‘crosslink and protein glycation’ play a role in ageing?

Answer 11

occurs in many bio molecules

cross linkage or bonds developed over time

alters physical and chemical properties

e.g. collagen cross links, glycosylation

Question 12

What is the role of ‘telomeres’ in ageing?

Answer 12

telomere = chromosome tail, repeated short DNA base sequence

stabilises chromosome during cell division

shortens with each division

critical length at which no further divisions can occur

in line with Hayflick phenomena

telomerase produced in germ and tumour cells

=> shortening of telomeres may affect gene expression and lead to senescence

Question 13

What is ‘somatic mutation and DNA repair’ in ageing?

Answer 13

exposure to radiation shortens life span (in mice)

ageing could be due to somatic mutate due to irradiation

caveats make theory less likely:

• occurrence rate to low
• DNA repair mechanisms sufficient to deal with damage from normal radiation levels

However, repair may fail in combo with other insults
e.g. ROS, UV etc

Question 14

What is the ‘free radical theory’ in ageing?

Answer 14

highly reactive chemical species from (non)-enzymatic reactions e.g. ROS

damage cellular DNA

protection usually by protector/scavenger enzymes
e.g. superoxide dismutase catalase)

protection reduces with age

Question 15

What is the ‘mitochondrial theory’ in ageing?

Answer 15

mitochondrial DNA damage

high exposure to ROS

mtDNA are not encased in histones

damage + mutation rates increase with age

genetic mitochondrial dysfunction can mimim ageing