Ageing Flashcards
What is ageing?
- progressive generalised impairment of function
- loss of adaptive responses to stress
- growing risk of age-related disease
What are the 3 theories as to why we age?
- wear and tear
- adaptive evolution
- non-adaptive evolution
What is the ‘wear and tear’ idea of ageing?
organism is a machine that wears out
inevitable price paid for complexity
caveat: not all animals age, e.g. those that have germ lines/stem cells to repair
What is ‘adaptive evolutionary’ theory of ageing?
- selectively advantageous to species
- evolution and natural selection
- Darwinian principles
caveat: ageing rarely seen in natural populations
What is the ‘non-adaptive evolutionary’ theory of ageing?
- accumulation of mutations over time
- natural selection declines with age
caveat: no experimental support
What is the role of ‘antagonist pleiotropic genes’ in ageing?
- early good effect therefore retained
- bad late effect contributing to ageing
evidence in drosophila
e. g. abnormal abdomen allele
- increased early function, reduced longevity over time
What is the ‘disposable soma theory’ of ageing?
- development of non-adaptive evolutionary views
- organism transfers free energy into progeny
- success -> ensures survival of genes
- disposable = limited lifespan
- soma = not of germ line
rate of ageing PROPORTIONAL to investment in self-maintenance
e.g. programmed to survive not age
How do we age?
4 categories
- system level theories
- cellular level theories
- genetic theories
- genomic stability
What is the ‘neuroendocrine theory’ in ageing?
functional decrease in neurones and associated hormone (central to ageing process)
HPA axis controls growth and development and putatively ageing
decreased pulsatile GH and GnRH (ageing rats)
hormone replacement increases lifespan
What is the ‘Hayflick phenomena’ in ageing?
fibroblasts have contact inhibition
more divisions if from a younger source/passage
biological clock
Hayflick limit is not usually reached in ageing organisms
may have important function in tumour regulation
How do ‘crosslink and protein glycation’ play a role in ageing?
occurs in many bio molecules
cross linkage or bonds developed over time
alters physical and chemical properties
e.g. collagen cross links, glycosylation
What is the role of ‘telomeres’ in ageing?
telomere = chromosome tail, repeated short DNA base sequence
stabilises chromosome during cell division
shortens with each division
critical length at which no further divisions can occur
in line with Hayflick phenomena
telomerase produced in germ and tumour cells
=> shortening of telomeres may affect gene expression and lead to senescence
What is ‘somatic mutation and DNA repair’ in ageing?
exposure to radiation shortens life span (in mice)
ageing could be due to somatic mutate due to irradiation
caveats make theory less likely:
- occurrence rate to low
- DNA repair mechanisms sufficient to deal with damage from normal radiation levels
However, repair may fail in combo with other insults
e.g. ROS, UV etc
What is the ‘free radical theory’ in ageing?
highly reactive chemical species from (non)-enzymatic reactions e.g. ROS
damage cellular DNA
protection usually by protector/scavenger enzymes
e.g. superoxide dismutase catalase)
protection reduces with age
What is the ‘mitochondrial theory’ in ageing?
mitochondrial DNA damage
high exposure to ROS
mtDNA are not encased in histones
damage + mutation rates increase with age
genetic mitochondrial dysfunction can mimim ageing
