Ageing
Biological theories
of ageing
Programmed ageing
The damage or error theories
belief that ageing is determined by our genetics
the same as how we are 'programmed' to grow
& develop during childhood
suggests our cells and tissues are progressively
damaged over time
Why do we age?
Oxidative stress
Mitochondrial dysfunction
Telomere length
region at each end of a chromosome,
protects
end of the chromosome from deterioration -
from fusion with neighbouring chromosomes -
maintained in cells by the
enzyme telomerase
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Telomeres
(region at each end
of a chromosome)
Protects
- end of the chromosome from deterioration
- from fusion with neighbouring chromosomes
Maintained in cells by
Telomerase
- maintain telomere length
- preserve cell function
(can't completely restore
telomeres)
Why it shortens
The length of telomeres
declines with ageing
due to successive cell divisions
where telomeres progressively shorten
When the cell can
no longer divide
it permanently arrests the cell cycle
(cellular senescence)
triggers cell death programmes
(apoptosis or autophagy)
Free Radicals
Main sources
of FR
Superoxide formed during oxidative phosphorylation
in Electron Transport Chain
Oxidative burst in phagocytes such as
macrophages
Caused by
Corporeal Factors
Environmental factors
- Aerobic respiration
- Metabolism
- Immune response
- Obesity
- Diabetes
- Exercise
- Injury
- Air pollution
- Asbestos
- Radioactive emissions
- Tobacco smoke
- UV radiation
- Trace elements - Fe, Cu
Effects of oxidative damage
oxidation of PUFA's in lipids
oxidation of amino acids in proteins
strand breaks in DNA/modification of bases
may cause heritable mutations
(in germ cells)
lipid peroxides -
involved in atherogenesis
may lead to formation of antibodies
against modified protein
may induce cancer
(in somatic cells)
lipid peroxides
break down to dialdehydes
which modify
proteins & nucleic acid bases
oxidised amino acids may catalyse
further formation of oxygen radicals
Fenton Reaction
(a reaction of transition metals
with oxygen radicals)
Metabolically important
metal ions
- iron copper
- manganese
- cobalt
- nickel
- zinc
- cerium
- chromium
This process converts hydrogen peroxide,
(a product of mitochondrial oxidative respiration),
into a highly toxic hydroxyl free radical
Thus, this reaction can
increase the levels of free radicals
Defences to FR
Protein binding of metal ions
(non-enzymatic)
Diet-derived antioxidants
(non-enzymatic)
Enzymatic
Catalase
Glutathione peroxidase
Superoxide dismutases
Copper bound by
ceruloplasmin
Metal ions bound by
metallothionein
Iron bound by
transferrin, haemosidierin, ferritin
ascorbic acid
(vit c)
Polyphenolics
(flavanoids, flavanones,
anthocyanins, resveratrol,
catechins)
a-tocopherol
(vit e)
Carotenoids
(B-carotene, lycopene,
zeaxanthin, capsanthin, l
utein)
Some antioxidants may be
pro-oxidants - cause oxidative damage
β-carotene may be an antioxidant at low partial pressure of oxygen but
pro-oxidant at high partial pressure of oxygen
Iron
Vitamin C
Vitamin E
Diet & the
ageing process
Caloric restriction
Rat studies
Research began in the 1930s to determine
the effect of restricted growth on life span –
(rats lived longer on energy restricted diets)
Is this due to
- reduced dietary intake?
- restricted growth?
- restriction of specific macro- or micro-nutrients?
This is an area of research interest
Calorie restriction delays
- many physiological ageing processes
- the onset and progression of most diseases of old age
(in rodents)
Since max life duration of rat is about 3yrs,
longevity studies may be completed in 5 years.
However, in humans the lifespan is 100+ years
so not been possible to carry out well-controlled
life-long studies to establish the effects of calorie restriction
Possible mechanisms
no general agreement on
anti ageing effect of food
restriction
Dietary restriction may reduce the concentration of tissue oxidative damage biomarkers (ie. peroxidation of membrane lipids, protein carbonyl formation, oxidative damage to DNA bases)
many sites and enzymes within cells where FR generated but mitochondria considered to produce the majority of cellular reactive oxygen species (ROS) during normal metabolism
A chronic reduction in mitochondrial ROS production has only been demonstrated in response to dietary restriction regimes in isolated mitochondria or cells using an in vitro approach. However, these methods are frequently conducted under non-physiological conditions, specifically with respect to oxygen levels, substrate concentration, and the presence of inhibitors of complexes of the electron transport chain
The majority of longevity genes in humans are involved in the insulin/insulin-like growth factor (IGF) pathway
Okinawa
Consequences
of Ageing
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Cardiovascular System
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Immune system
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