Theories of ageing Flashcards
There are 3 major groups of theories as to why we age
Wear and tear.
Adaptive evolutionary.
Non-adaptive evolutionary
Describe wear and tear, and what opposes this theory
The wear and tear theories view the human body as a machine that wears out, due to cumulative damage
Eg elephants= 26 teeth, use only 4 at a time. Once those 4 are worn flat, they move to the next 4. Once all teeth flatten, they cannot chew–> die
BUT some animal models oppose wear + tear
The sea anemone doesn’t age and their germ line is also maintained, unlike in most other animals
Some animals regenerate whole limbs, eg salamanders
This shows the ability we have to repair, so ageing must more complex than just damage accumulation
Describe Adaptive evolutionary theory, and what opposes this theory
Adaptive evolutionary=ageing developed thru evolution and natural selection
This suggests that ageing is selectively advantageous– perhaps as it prevents old individuals competing w upcoming generation
BUT, ageing is an advantage to the population, not an individual, hence natural selection can’t explain it
Ageing also rarely seen in natural pops. Most die before significant ageing.
Due to this, most people don’t believe ageing= a characteristic that has positively been selected for
There are 3 major groups of theories as to why we age:
Describe non adaptive evolutionary, and what opposes this theory
Non-adaptive evolutionary: ageing=by-product of evolution
There are 2 theories: Mutation accumulation and Antagonistic pleiotropic genes, which combined have a mathematical ageing model called the disposable soma
What is mutation accumulation?
Mutation accumulation=natural selection powers decline w age
Genes expressed early will affect most of the pop, before they have a chance to breed. Genes expressed after reproduction are lost from evolutionary control
Therefore ageing occurs due to collection of late acting deleterious genes
BUT there is no experimental support for this theory
( This theory suggests that natural selection is not effective in preventing age-related decline, as the selective pressures of reproduction are removed after a certain age. )
What are Antagonistic pleiotropic genes?
Antagonistic pleiotropic genes are genes w good effect early on, therefore are retained during evolution, but later on have bad ageing effects
Some evidence for this from drosophila (fruit fly) studies. Similar studies in humans are not easy as we age slow
The drosophila studies found the following:
- The aa (abnormal abdomen) allele greatly increased early fecundity , but pleiotropically reduces longevity
- If breeding is prevented until later life, the lifespan is extended by 1/3, but the progeny are short winged + have a reduced ability to fly
What is the disposable soma theory?
(In biology, “soma” refers to the body of an organism, excluding the germ cells (gametes) that are responsible for reproduction. )
The disposable soma: organism= a machine that transfers free energy into progeny - Success is ensuring gene survival into the next generation in the most efficient way
Essentially, the germline must be preserved & passed on, but the body is a disposable!!!
The theory works as follows:
- An organism can take in a set amount of energy
- That energy must be distributed between vital tasks
- Maintaining your own body & repro also require energy, but are less essential, therefore how much energy we put into that may vary
Maintaining your own body and reproduction also require energy, but are less essential, therefore how much energy we put into that may vary
Use an example of a cat and a mouse to describe this analogy
Mice could’ve adapted to put mucho energy in maintaining their body to enable long life. BUT cat eats the mouse and benefits from such maintenance (protein rich).
Mice die of predation, not ageing, so the best way to pass on genes= breed young + rapidly!
Cats, however, must raise + teach kittens to hunt (takes long). So, cats must live longer para pass their genes on to offspring capable of surviving, which hinders their fertility. Same idea for humans
Disposable soma model: energy expended on vital tasks depends on the organism’s ecological niche - This will result in species specific longevity
For some, fertility is priority - not soma (e.g. mice), but others must maintain their soma for longer (e.g. cats, humans)
What is Another View on the Disposable Soma Theory?/ how does physics support it?
From the 2nd law of thermodynamics, entropy increases - When applied to this context, it means we age and decay
Our bodies resist this w defensive and repair processes, though these protective mechanisms will eventually fail
Ageing rate is determined by the amount of energy invested in self-maintenance as opposed to other tasks
In other words, we are programmed to survive, not to age, but eventually our resistance to ageing breaks down
What is the neuroendocrine theory of ageing?
The neuroendocrine theory: a functional decrease in neurones + hormones is central to the ageing process
The HPA axis controls development, so maybe ageing too? In ageing rats, there is decreased pulsatile release of GH and GnRH from the pituitary
Hypophysectomy (removing the pituitary) and subsequent hormone replacement increases the rat’s lifespan
A death hormone (DECO) produced from the pituitary was proposed, though this was never found
What are the cellular and molecular theories of ageing?
Wear and Tear
- Metabolism: generally, animals w higher BMR= shorter lifespan
- Cross-linking: Molecules develop cross links over time, altering their properties. Eg collagen, where cross-linking of fibres in the skin as we age reduces how stretchy the skin is
- Heat Shock Proteins: disassemble damaged proteins, transport new ones into cell during stress. HSP production reduces w age. Less able to cope with stress–> ageing
Interestingly, surgical scars in the elderly=smaller and neater, though functionally not as strong. This is bc the healing process is not as intensive due to reduced HSP
What is the hayflick phenomena? ( a cellular/ molecular theory)
Hayflick Phenomena: Fibroblasts grown in culture undergo a set number of divisions then stop. Division number is increased if cells were taken from a younger source
Suggests there may be a bio clock that limits the n0 of cell divisions- after a set n0, cells cannot divide/ be replaced, damage accumulates–> age
BUT most elderly still have significant cell division–Hayflick limit not reached
Furthermore, certain cell lines, such as HeLa from breast cancers have unlimited division. So Hayflick phenomena is relates to tumour suppression – in order for a cancer to develop, it must overcome the Hayflick limit
(In summary, the Hayflick phenomenon describes the limited number of cell divisions that normal human cells can undergo before reaching a state of replicative senescence. While it suggests the presence of a biological clock that limits cell division and contributes to aging, other factors play a role in the aging process, and cancer cells can bypass these limitations, leading to uncontrolled cell division and tumor formation.)
Genetic theories centre round the idea that certain genes alter the rate at which we age - Expand on these theories:
Geronto-genes increases ageing rate, whilst longevity assurance genes slows age
There is definitely a genetic influence on ageing:
Twin studies: closer genetic individuals are more likely to have the same lifespan
Long lived families: genetic tendency to live longer in some families
Species specific longevity: genetic differences between species affect longevity, eg mice live 2 years, we live 75yrs
In nematodes, a mutation that doubles their 3 week lifespan by increasing superoxide dismutase
What are telomeres and how do they affect ageing?
Chromosome tail, repeated short base sequence.
Stabilise chromosome in division, shorten every division.
Critical length at which no further divisions can occur (Hayflick phenomena).
In germ/tumour cells telomerase produced-repairs the telomere. In cancer cells, telomerase allows bypass of Hayflick limit
A study in mice found that if telomerase is knocked out, the mice age very quickly and developed dementia. This was mostly reversed when they were given telomerase
In a study of men w low risk prostate cancer lifestyle changes–> reduced oxidative stress–> longer telomere + increased telomerase activity. Telomere length also regulates ISG15 expression in human cells, a gene involved in immune system function.
Genomic stability theories - What is error catastrophe?
Errors occur at transcription and translation that result in abnormal protein production.
Usually corrected when protein ?
If protein important in DNA repair or protein synthesis may lead to a cascade and cell death.
Accumulation of such errors may result in ageing.
This is a neat idea on paper, but it doesn’t work mathematically –required number of such errors=too large
What is the somatic mutation and DNA repair theory?
Theory is that background radiation causes somatic mutations in mice, leading to ageing
We now consider somatic mutations less important because they occur too slowly, and DNA repair is often sufficient enough not to cause any issues
But also note:DNA repair is more efficient in man than mice
It’s more efficient in Germ cells
It declines with ageing (more cancer cells are seen)
5 factors which cause cell senescen?
What is cell senscence?
Senescence alters gene expression. There is upregulation of genes controlling ECM degrading enzymes, inflammatory cytokines and growth factors, leading to disruption of normal tissue structure and function, as well as stimulating the growth of pre-malignant cells
What factors cause ageing?
A whole host of factors contribute to ageing, and we can think of it as a balance between factors that promote self-maintenance, and factors that promote ageing
Factors that promote ageing include protein glycation, irradiation, UV light exposure and free radicals, along with geronto-gene influences
Factors that try to counter this include free radical scavengers, protective enzymes, HSPs, DNA repair mechanisms and longevity assurance genes
What is hormesis?
