AHHHHH Flashcards
Medawar theory of ageing
Why did natural selection make us all immortal? There are organisms that don’t become more likely to die as they get older
George Williams
Peter Medawar
The declining force of natural selection with age
Gene that makes heart explode - if it makes your heart explode as you are born natural selection would remove it (can’t pass gene on)
If the gene makes your heart explode when you are 50 the gene will be passed in more easily. Being removed by natural selection will happen more slowly.
Why Huntingdon disease is common:
It was so common because the symptoms don’t appear into late thirties so you can have already have kids before this
Before civilisation humans lived shorter ANYWYS so getting a bad disease may not have made much of a difference to how many kids you have
Even if we didn’t age we would still die from other factors
Mutation accumulation hypothesis -
Genes responsible for ageing are genes that have bad effects that don’t appear until the age at which we wouldn’t have been alive anyway so these genes were passed on in natural selection (because people died before they were put into action any way so they weren’t seen as bad by natural selection)
If we see an old animal it’s usually because we have protected sit from predators etc so only now do we get to see the genes responsible for ageing
Civilisation and sanitation means humans now see the effects of ageing genes because we haven’t died by the time they come into action
Medawar - thought genes responsible for ageing would be silent and then have a bad effect later in life (silent then bad effect)
Williams - gene could have different effects early in life than late in life. Gene that when you are young helps calcium in bones but when you are old contributes to calcium in arteries. (Early good effect then bad effect)
Antagonistic playotropy hypothesis
Disposable solar theory - economics and biology, can’t get more of one good thing without giving up sm else.
Early good effects are reproducing more and the bad layer effect is dying sooner
11 causes of biological ageing at cellular level
Double or single strand breaks
Damaged DNA activates PAROs (DNA repairing proteins) that can exhaust supplies of NAD+ which supplies energy for anti ageing processes.
Telomere shortening
As epigenetics mechanisms decline with age genes may be be activated incorrectly
Unfolded or misfiled proteins. Build up of these proteins
Mitochondrial dysfunction. Can happen without significant damage or mutations of mitochondrial DNA
Cell senescence - cells stop dividing, secrete inflammatory molecules, accumulate over time and damage becomes more pronounced
Stem cell exhaustion (stem cells are undifferentiated cells). Stem cells allow for the renewal of cells within an organ.
Glycation - sugar molecules in blood stream bind to proteins and fats resulting in harmful molecules called advanced glycation end products (AGEs). Nasty effect on skin - cause collagen and elastin to become discoloured and weak = wrinkles
AMPK pathway.
ATP converts to AMP. Rising levels of AMP and declining ATP causes activation of enzyme called AMPK, this enzyme promotes rapid efficient release of energy with little energy stored as fat resulting in low blood sugar and fat levels increases insuline sensitivity and a low risk of heart disease diabetes. Critical to immune system and reduces inflammation.
AMPK levels decrease with age, these processes decline and this leads to ageing.
Chronic inflammation, declining immune system - body release pro inflammatory signals like cytokines and reactive oxygen species which cause oxidative damage to cells and tissue.
mTOR pathway. HGH/IGF-1. Master regulator of anabolic metabolism - process where new tissue is built. Regulates cell growth, proliferation, Mortality, protein synthesis transcription. mTOR is activate by insulin like growth factor 1, a derivative of human growth hormone. mTOR is great for growth but bad for life spans.
Trade off - fast growth but shorter life span
Sirtuins - longetivity genes. Regulate mitochondrial biogenesis, stimulate autophagy and apoptosis, inhibit inflammation. Three are involved in repair of DNA. Can only function in presence of NAD+ which declines with age. As this happens the production of sirtuins also decreases.
Sirtuins
7 different proteins that play a critical role in regulating cellular health
NAD+ is a derivative of vitamin
B6
X
PARPs - Poly ADP Ribose Polymerase
Consume NAD+
PARPs repair mutations in DNA when it replicated to prepare for cell division
Activating NAD dependent molecules (sirtuins and PARPs) can lead to NAD supply exhaustion.
P53 responsible for elimination of carcinogenic cells. Activation of PARP enzyme indices over expression of P53
