Theories of ageing

Question 1

LIFE EXPECTANCY

i) what is average LE from birth in males and in females?
ii) what is avg LE from 65 in males and females?
iii) what is lifespan?
iv) what is healthy life expectancy?
v) what two things balance out meaning that there is not really much change in life expectancy?

Answer 1

i) males - 79 and females 82
ii) 86 for females and 83 for males
iii) maximal potential for a species - around 129 for himans
iv) the amount of time people spend in good health

v) balance between compression of morbidity (drivers of inc LE also delay onset on NCDs)
and expansion of mortality (early onset of NCDs)

Question 2

AGEING

i) what is chronological ageing?
ii) what is biological ageing?

Answer 2

i) how long you have lived in years
ii) how old is your body - progressive loss of function/ steady decrease in physiol ability with inc chronological age

Question 3

INFLAMMATION

i) what happens to inflammation in older people? what does this lead to and what may it contribute to?
ii) name three inflammatory factors that may be raised in elderly people

Answer 3

i) they can mount an imm response but fail to turn it off effectively > leads to low level inflammation > may contribute to chronic diseases

ii) mild chronic elevation in cytokines/acute phase reactants
- IL-6, TNFa, CRP

Question 4

PROGRAMMED VS NON PROGRAMMED AGEING

i) what is programmed ageing? what is non programmed?
ii) what is antagonistic pleiotropy?
iii) what are the three groups that make up hallmarks of ageing? explain each

Answer 4

i) follows a biological timetable > drawn from evolutionary theory
- non programmed is driven by disease processes

ii) preserving gene functions that are advantageous when you are young but not when you are old

iii) primary hallmarks > cellular and macromolec damage
antagonistic hallmarks > initial mitigation of damage - if ongoing becomes damaging
integrative hallmarks > end result that is responsible for func decline assoc with ageing

Question 5

PRIMARY HALLMARKS

i) name two exogenous and two endogenous things that cause genetic instability?
ii) name three things that can affect epigenetic alteration?
iii) why is there a reduction in telemore length which each cell cycle? what is replicative sensence?
iv) what can cause abnormal protein folding? what happens with age? give two examples of conditions that implicate these

Answer 5

i) exogenous > UV, enviro toxins, viruses
endogenous > DNA rep errors, ROS

ii) stress, enviro factors, disease states

iii) because most cells lack telomerase
- rep senescence > telomere exhaustion (gets shorter) > cell undergoes apop

iv) stress > abnormal folding
- with age, unfolded protein sensors fail > accum > cell dysfunction
- alz and PD

Question 6

ANTAGONISTIC HALLMARKS

i) how is nutrient sensing implicated in creasing age? what can calorie restriction improve? what does mTOR sense?
ii) how it mitochondrial dysfunction implicated in ageing?
iii) what is cellular senescence? what two things can happen to these cells

Answer 6

i) dysregulated sensing
- calorie restriction can improve insulin sensitivity
- mTOR senses high amino acid concentrations

ii) progressive dysfunction > get more free radicals > damage to proteins, nuc DNA and mito DNA (global cellular dysfunction) in muscles
iii) stable arrest of the cell cycle > cells can be removed or stay there and secrete inflammatory mediators > inflammo ageing

Question 7

INTEGRATIVE HALLMARKS

i) what happens to stem cells with age? name five consequences of this
ii) what is the bystander effect?

Answer 7

i) stem cell exhaustion > anaemia, osteoporosis, decreased fracture repair, reduced muscle fibres, reduced intestinal function
ii) senescent cells trigger sensescence in other cells

Question 8

PREMATURE AGEING SYNDROMES

i) which gene is implicated in wereners syndrome? what is the inheritance pattern?
ii) when is the onset of symptoms in wereners syndrome? what happens
iii) what is the gene defect in hutchinson gilford progeria syndrome? what does the gene do?
iv) what is the inheritance pattern of HGPS and when is the onset?

Answer 8

i) wereners > WRN gene that encodes DNA helicase
- auto recessive

ii) onset in teens > premature ageing due to somatic DNA damage
- accelerated age related diseases eg athero

iii) gene defect in lamin-A > abnormal nuclear struc and func therefore exposure to lots of DNA damage and error
- advanced aged related conditions

iv) autosomal dominant > onset in first two years of life (death by 13)

Question 9

SUMMARY

i) what is the main risk factor for common chronic diseases?
ii) what are the four things related to age related dysfunction and chronic disease?
iii) name two non genetic factors that can modulate rate of build up of damage?

Answer 9

i) chronologic age
ii) chronic/low grade/sterile inflammation, cellular senescence, macromolec dysfunction, stem cell progenitor dysfunction
iii) nutrition and exercise