Theories of ageing 02/04 Flashcards
When does senescence (ageing) begin?
65+
Technically, ageing begins at the beginning of life.
However, age related decline begins in many tissues from around 30 years onward such as: - speed of nerve conduction - volume of blood pumped by heart per min - kidney filtration rate - lung capacity
Define functional reserve capacity
Many organs have a ‘reserve capacity’, which allows them to maintain homeostasis even though their functional capacity is declining. When the reserve capacity is exhausted (i.e., functional capacity has declined to the minimum threshold), homeostasis can no longer be maintained and the system goes into failure.
What is the theory of programmed ageing?
A deterministic theory of ageing, which states that genome contains a set of ‘self destruct’ instructions (i.e., genes) that are activated at a certain point in their life cycle.
What five pieces of evidence are given for programmed ageing theory?
- Species - specific lifespans
- Twin studies
- Limited cell division - Hayflick limit
- Fast ageing syndromes - progeria
- Gerontogenes
Species - specific lifespan evidence for programmed ageing?
Throughout species there is a wide range of lifespans, and therefore it was proposed that this is because the genes for an ageing system switch on at different ages. It was considered to work much like genes for sexual maturity, switching on at a specific time point. Maximum lifespan also correlates well with reproductive age, which was suggestive that there could be a link between these two gene systems.
The theory that the maximum life span of an organism is intrinsically limited and is largely species-specific necessarily involves certain notions of genetic regulation - however the evolutionary adaptiveness of a programmed theory of ageing is not tenable
Twin study evidence for programmed theory of ageing?
Average age of death is smaller in monozygotic twins than dizygotic twins or random individuals (no difference between dizygotic and random).
Across the entire lifespan, genetics account for 24% of the variation (modest effect size).
However, after the age of 70, genetics account for 50% variation - supporting the idea of a ‘switched on’ system of ageing.
Hayflick limit for programmed ageing
Hayflick limit - maxmimum number of cell divisions. (Some cells such as sperm, epidermal etc do not have hayflick limit but most do).
Sensencent fibroblast cells show morphological changes, secrete proteases, secrete pro-oncotic factors. Population doubling of fibroblasts correlates with maximum life span. So perhaps the dangers of senescent cells is the evolutionary purpose for this halting of cell cycle
Why do telomeres provide evidence against programmed theory of ageing?
Telomeres buffer coding regions from the loss of DNA occuring during replication (Okazaki fragments). They also prevent abberant fusing of chromosome sticky ends. They also act as a biological clock - minimum length halts cell cycles.
Therefore ageing occurs not due to a programmed system but due to imperfect copying of DNA.
Progeria evidence for programmed ageing
Fast ageing sydrome - werner sydrome/progeria. Accelerated ageing in many tissues such as skin, cardivascular, type 2 diabetes, artheritis. Some age related changes not seen such as neurodegeneration.
Mutation in the helicase gene - unzips DNA during mitosis for DNA replication. No DNA synthesis or cell division halts. Cells are therefore reaching sensecence very early.
Why Progeria does not provide evidence for programmed ageing
No - fast ageing of cells/organs is due to very poor
- copying of DNA,
- repair of DNA -
production of new proteins
i.e. poor cell ‘maintenance’ activity because they do not have functioning helicase
Gerontogene evidence for programmed ageing theory
Gerontogenes are any genetic elements that control processing of ageing and lifespan. When mutated, their expression usually increases.
Mutations in AGE-1 and daf gene doubles the lifespan of c-elegans.
Mutations in anti-oxidant systems (increasing activity) increases fly lifespan by 30%
Why gerontogenes are not evidence of programmed theory of ageing?
Mutations in AGE-1 and daf alter insulin signalling in cells (calorie restriction).
Antioxidant mutations decrease free radicals.
These mutations are having effects on factors that contribute to random wear and tear damage (non-deterministic theory of ageing). They are not part of a programmed ageing system, but of systems evolved to reduce cellular damage. These genes are involved in longevity and homeostasis - they are not selected as ‘ageing’ genes, but ageing is an emergent property of these genes.
Define an ageing population
One in which the proportion as opposed to the absolute number of people aged 65+ is increasing
