Ageing Flashcards
What can live more than 5000 years?
Pinus longaeva (Bristlecone tree)
What is the molecular basis of longevity?
Somatic maintenance
What is regenerative medicine?
Uses stem cells to replace ageing tissues and organs
What can ageing refer to?
Progressive deterioration of cells, tissues etc, associated with increased age, but also maturational changes, which are positive, such as getting wiser, evolution of lifestyle etc.
What is Michael Rose’s definition of senescence?
“The decline of fitness components of an individual with increasing age, owing to internal deterioration”
What is the difference between ageing and senescence?
Senescence only refers to the progressive deterioration- ageing may also refer to the positive aspects.
What is gerontology?
The scientific study of the biological, psychological and sociological phenomena associated with old age and ageing.
What is geriatrics?
The branch of medicine that deals with the diagnosis and treatment of diseases and problems specific to the aged.
What is biogerontology?
The study of the biology of ageing and longevity
What does demography refer to?
The study of the characteristics of human populations, such as size, growth, density and distribution of vital statistics.
Give one way to express the pattern of death or mortality in a population?
Survival curves.
How can lifespan be expressed?
As life expectancy from birth or from a later age
What is the difference between changes in life expectancy from 65 and that from birth?
LE has changed hugely from birth over time (due to reduction in infant mortality) but from 65 it has changed little.
What is median lifespan?
The age at which 50% of he population have died.
What is maximum lifespan?
The age at death of the last surviving individual in a population cohort.
How have improvements in health and sanitation affected the different ways to express lifespan?
They’ve increased the mean and median lifespan but have changed the maximum lifespan little.
Who was the longest-lived human verifiable?
Jeanne Calment- lived to 122
What is a current estimate of maximum lifespan in english women?
That 1.6% will live to reach 100.
What is the gender gap?
5-7 years in LE from birth
What is thought to be the reason for the gender gap?
Due to endocrine differences, effects of testosterone on male behaviour and physiology.
What is mortality rate?
The probability that an individual who is alive at a particular age will die during the following age interval- typically a year in humans.
What is the Gompertz law?
Mortality rate increases exponentially with increasing age. Acceleration in mortality rate as you get older- demographic senescence.
Describe a lot plot of mortality and age.
Mortality increases as a linear function of age, except for the “hump” around 20 years- reckless and dangerous decisions.
What is the Gompertz parameter?
The slope of the log of mortality against age.
How can demographic ageing be expressed?
As the rate of increase in mortality rate in the form of mortality rate doubling time (MRDT).
What is MRDT?
Mortality rate doubling time: The time required for the mortality rate to double (to be twice as likely to die)
What is the MRDT in humans?
8 years
What are the three major aspects of biogerontology?
Evolutionary biology of ageing, traditional gerontology (biological mechanism) and model organism lifespan genetics.
What was first thought to be the reason for ageing evolving?
To be for the good of the species, to remove worn out individuals and reduce the competition for limited resources.
Who had the first insight into evolution of ageing, and what were they studying?
J.B.S. Haldane. Studying Huntington’s.
What is Huntington’s?
A genetic, neurodegenerative disease caused by a highly penetrant dominant mutation.
How did Haldane reach his conclusions? (ageing)
Av. age of Huntington’s onset= 35.5 years- natural selection hasn’t removed it because for most of evolutionary history people didn’t live that long, so selection pressure to remove the mutation is weak, as it’s after children have been born.
What was Haldane’s conceptual leap?
The later the timing of onset of a deleterious effect, the weaker the force of natural selection acting against it, predicting an accumulation in the population of late acting deleterious mutations.
Who developed the mutation accumulation theory?
Peter Medawar
What is the mutation accumulation theory?
Even in a population free of ageing, death will occur, from extrinsic hazards such as disease, predators and accidents. Recurrent, deleterious germ line mutations occur, and fewer bearers survive to express later- acting mutations. The force of natural selection against them declines with age, and these mutations can therefore reach a higher frequency under mutation- selection balance. There’s a strong force of natural selection on early acting mutations but not late acting mutations, as fewer bearers are still alive.
Who came up the the pleiotrophy theory of evolution of ageing?
George Williams
What are other names for the Pleiotrophy theory?
Trade-off, antagonistic pleiotrophy
What is the pleiotrophy theory of the evolution of ageing?
Ageing evolves as a side-effect of natural selection in favour of mutations that cause a benefit during youth.
What is the reasoning behind the pleiotrophy theory of the evolution of ageing?
Some mutations may be beneficial in youth but have a higher rate of ageing; more individuals will survive to express the early benefit than survive to suffer higher rate of ageing due to extrinsic factors. Such mutations can be incorporated by natural selection.
What is the adaptive value/ purpose of ageing?
There isn’t any.
What were Loeb and Northrop’s findings (ageing)? What coefficient did they find?
That increasing temperature reduces Drosophila lifespan. Coefficient relating lifespan to ambient temperature = 2-3. The biochemical reactions constituting life processes happen faster at higher temperatures.
What did Miquel (1976) find about lifetime oxygen consumption vs physiological temperature range?
That it was constant from 18-27 degrees C (physiological temp). Value for 27 degrees c slightly lower- at top end of physiological range for Drosophila - reflects high rate of living and thermal injury.
What is the Rate-of Living Theory?
Pearl (1928). Metabolism rate critical in ageing. “The duration of life varies inversely as the rate of energy expenditure… the length of life depends on the rate of living”. Life energy potential is constant.
What is the free radical theory of ageing?
Harman (1956): Ageing results from damage to macromolecules caused by free radicals.
What is a free radical?
Any species capable of independent existence that contains one or more unpaired electrons. They are usually highly reactive
Why may free radicals cause damage and thus ageing?
Superoxides can react with DNA, with lipid and with protein.
What are some examples of radicals in the body?
Superoxide, hydroxyl, peroxyl, alkoxyl, hydroperoxyl.
What are some examples of non-radical superoxides?
hydrogen peroxide, hypochlorous acid, ozone, peroxynitrie.
What theory does it make more sense to talk about than the free radical theory of ageing?
The oxidative damage theory of ageing.
How could you link the free radical theory of ageing to the rate-of-living theory?
Mitochondrial oxidative phosphorylation generates superoxide. Hence higher metabolic rate results in more free radicals and therefore faster ageing
What is the the pre-1961 view of cellular senescence?
“All metazoan cells (replicating somatic cells e.g. fibroblasts) are potentially immortal. Ageing not cell autonomous.”
What did Hayflick and Moorhead do in 1961?
Isolated cells from human tissue and cultured them- cells divide and form confluent layer on vessel surface. Discarded half of these, allowed remained to grow to confluency (one passage). Continued to passage the cells.
What did Hayflick and Moorhead find (1961)?
Passaged normal cultured human cells eventually lose their capacity to replicate, after 50 +/- 10 passages. Reach the HAYFLICK LIMIT and undergo replicative senescence.
Why was Hayflick’s finding shocking?
It implied that cell biology could explain ageing; organismal ageing was due to morphological change.
Give two examples of very closely related species and how they differ in lifespan.
Chimpanzee (59 years) and humans (110). C. elegans (3 weeks) and Loa loa (20 years)
What is the classical genetic approach to ageing?
1) isolate mutants with altered rates of ageing2) map, clone and sequence genes concerned3) identify lifespan-determining proteins, biochemistry, etc.4) Understand ageing!
What is the advantage of the classical genetic approach to ageing?
It requires no prior hypotheses about the biology of ageing.
What are the four model species for lifespan genetics? What do they all have?
Saccharomyces cerevisae, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus.They all have sequenced genomes and extensive classical genetics.
