Download The Ageing of Science

The Science of Ageing
Fergus Doubal
12th December 2006
Concepts
Impact on the organism
Demographic shifts in populations
The Science of Ageing
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Aging v ageing
Why is it important/interesting to you?
Why can I talk about it?
Relative
Hill 1915
Questions
• Do we age (and does everything)?
• Why do we age?
• How do we age?
Sources
• Wellcome Trust booklet on Ageing
• Cell 2005 – Vol 120
• Online lectures from Dr David Gems –
University College London
• The odd paper
Do we age?
• Ageing – progressive loss of function with
dec fetility and inc mortality with inc age
• Senescence – the deleterious effects of
ageing
• Think of yourself
• Think of others
• Best way of deciding if species age is by
determining if the age specific mortality
increases
Graphs showing age specific death
rates
Log
death
rate
Death
rate
Age
Age
For humans our chances of dying from ageing related processes
doubles every eight years
What is happening to us?
• Demographics – change in life expectancy
from decrease in infant deaths
• Speak about external mortality (as it
decreases maximum lifespan increases)
• Speak about the evolutionary unique
position we are in
• The very old ie above 95 are not dying at
an increased rate (interesting and
confusing)
The numbers game
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2000 – 600 million >60y
2025 – 1.2 billion >60y
2050 – 2 billion >60y
In dev countries >85y is the fastest
growing section of society
• Women outlive men almost in all societies
WHO figures
Do we age?
• Yes
Why do we age?
• Conversely why are we here in the first
place?
• Are we here purely to pass on our genes –
therefore women become disposable after
the menopause and men become more
useless the older they get
• Rather disappointingly there have been
over 300 theories of ageing published
Evolutionary theory 1
• Senescence programmed to get rid of old
useless individuals (limiting pop size and
accelerating the turnover inc natural sel)
• But this does not actually happen – ageing in the
natural world does not kill animals as extrinsic
mortality is too high
• So animals do not live long enough to grow old
and natural selection is not able to effect ageing
Evolutionary theory 1
• For the greater good of the species old
individuals should die
• But natural selection acts at the level of
the individual not the species
• Therefore even though it may seem an
overall good idea try telling that to the ant
on the street (and any pro-ageing gene
would be disadvantageous to the holder)
Evolutionary Theory 3
- “Mutation accumulation”
• Gradual accumulation of late acting alleles
that have not been selected out as the
natural selectin pressures are low at
advanced years
• This gradual accumulation subtly affects
the species and thus ageing occurs
Evolutionary Theory 3 –
“Antagonistic Pleiotropy”
• We age because genes have two effects.
• One early good effect and one late bad
effect.
• Eg Testosterone – psych hospital study
• Contribution to fitness is composite of both
the size of the effect and the prob of
surviving to benefit
• Life history trade off
Evolutionary theory 4 –
“Disposable soma”
• Each organism has a finite amount of
metabolism
• It needs to pass on its genes in its lifetime
• Needs to allocate its energy between itself
(soma) and its germ line
• Eg if it take on average 3 years to find a
partner then the organism needs to
survive for at least 4 years.
Disposable soma continued
• Take mice. 10% survive the first year therefore
they need to concentrate on finding a mate in
the first year. The mouse gives energy to
reproduction and passing on its germ line rather
than to looking after its own body
• As it does not look after its DNA it becomes
damaged and ages after about 2 years but it
does not matter because it is dead by then
anyway.
• Intrinsic mortality is linked to extrinstic morality
eg bats
Why do we age?
• Because after having diverted our energy
into producing offspring our bodies neglect
to look after their own DNA which leads to
a general loss of function
How do we age?
• Very complex
• Likely to be due to many genes and
downstream genes acting at various
timepoints.
• I will start at the molecular level and then
work up to the cellular and then
mammalian level finishing off with “I do not
really know but it is probably due to insulin
and oxidative stress somehow”