Dietary Restriction Flashcards
what are the common ageing-associated pathologies? (5)
- cardiovascular eg atheroscleorsis
- central nervous system- parkinson and lazheimers
- special sense- catracts, macular degeneration
- endocrine- non-insulin dependent diabetes
what is the general protocol of dietary restriction?
60-70% ad libitum food levels- sufficient vitamins, minerals
what are the effects of DR on rodents?
- post-poned age related decline in blood glucose control, female reproductive capacity, DNA repair, immunity, learning ability, muscle mass, protein synthesis
- slow age-related increases in: cross-linking go long lived proteins, free radical production by mitochondria, oxidative damage to tissues
- delays the onset of late-life diseases: autoimmune disorders, cancer, cataracts, diabetes, hypertensions
- Most importantly: 20-40% increase in lifespan
in rodents, what is the increase in lifespan seen after dietary restriction?
20-40% increase in lifespan and extension of youthspan
what age-associated disorders are delayed in mice that undergo DR?
autoimmune disorders, cancer, cataracts, diabetes, hypertensions
in rodents, what does DR slow the increases of?
cross-linking go long lived proteins, free radical production by mitochondria, oxidative damage to tissues
in rodents, age-related declines in what are postponed?
blood glucose control, female reproductive capacity, DNA repair, immunity, learning ability, muscle mass, protein synthesis
what is the difference between dietary restriction and calorie restriction?
dietary restriciton suggests that i is the reduction of a component of the diet rather than of just calories no matter what the content
what is the evidence for calorie restriction rather than DR?
- animals are put on diet of around 50% of voluntary intake
- this expands the lifespan in organisms ranging from yeast to mammals and maybe primates- it does in c.elegans, drosophila and mouse
- it decreases the induced of virtually all age-related damage and disease
describe a study that looked at the effects of long term DR in humans.
18 subjects were put on DR for average of 6 years- there was reduced serum cholesterol, triglycerides and insulin, lower blood pressure too. Most importantly array wall thickness was reduced by 40%
in the human study, what were the results of DR for 6 years?
reduced serum cholesterol, triglycerides and insulin, lower blood pressure too. Most importantly array wall thickness was reduced by 40%
what did the test of DR on humans suggest?
that DR can protect against atherolsclerosis
what is the place where there are highest fraction of centenarians in the world called and hw many are there?
Okinawan, 18.5 per 100,000 population
what is the difference between the diet of the children and the adults in okinawan?
the children eat 60% of recommended diet and adult east 20% less.
how do the people of okinawan japan compare to americans in terms of age related disease?
- 75% more likley to retain cognitive abilities,
get 80% fewer great and prostate cancers and less heart attacks
what is the example of DR in trees?
Very long-lived trees found in very poor soil- bristleconeis 5000 years old
what needs to happen with the study of DR in humans before any conclusions can be drawn?
will have to wait and see if these people live longer
what are the 7 main theories of how DR/CR works?
retardation of growth theory, reduction in body fat hypothesis, reduction in metabolic rate hypothesis, oxidative damage attenuation hypothesis, altered glucosee-insulin system hypothesis, alteration of the growth hormone IG-1/axis hypothesis, hormesis
what is the theory and what were the reasons for and against the retardation of growth theory?
- CR increases the longevity of rats by retarding growth. this held sway because many felt that ageing was a continuation of development.
- However, this was disproved by the experiment which as to CR from 6 weeks of age, between the weeks of 6-26 weeks and from the weeks 26 onwards. This showed that DR during development and growth was not required for life extension
what is the rate-of-living theory and what is the evidence for an against?
This is the theory that metabolic rate is decreased when rats undergo DR and that this decrease is what extends longevity.
evidence for:
- reduction in food intake by humans reduced metabolic rate
- there is an inverse relationship between species longevity and its metabolic rate per kilogram body mass.
Evidence against:
- In male mice, following the exposure to DR, there was a brief period of reduced food intake per gram body mass, this was followed lifetime intake greater per gram body body weight in the CR- assuming the lifetime of intake of calories is a valid ind of lifetime choleric expenditure- CR rats has a markedly greater lifetime caloric expenditure per gram body weight
- the same was found in rhesus monkeys
reports show that in mice- a positive correlation between metabolic rate and longevity
how is the “rate of living” theory measured?
caloric intake/ expenditure (metabolic rate) per gram body weight
what is the oxidative damage attenuation theory?
- theory that ageing is due to damage caused by free radicals, with the metabolic use of oxygen being the major biological source of free radicals. These molecules can cause damage important biological molecules such was DNA, proteins and lipids, thereby altering cellular functions.- many believe that the accumulation of this damage is the primary basis of ageing.
the idea is that CR attenuates this damage. CR has been shown to retard the age-associated accumulation of oxidatively damaged molecules in rodents and there is evidence it acts in the same way as monkeys - this attenuation of the accumulation of oxidative damage must be due to either a decrease rate of generation of reactive oxygen molecules or to increase efficiency of protective processes or to an increase in repair activity or a combination.
wat are the two main free radicals and one damaging reactive oxygen molecule?
- hydroxyl and superoxide radicals
- hydrogen peroxide
what is the evidence for the oxidative damage attenuation theory? (6)
the idea is that CR attenuates this damage. CR has been shown to retard the age-associated accumulation of oxidatively damaged molecules in rodents and there is evidence it acts in the same way as monkeys
- there is evidence that CR decrease the formation of reactive oxygen molecules by isolated mitochondria and microsomes from CR rodents but there is little in vivo insight.
- many studies have shown that CR increases the activity, or retards the age-associated decrease in activity, of enzymes like catalase, superoxide disputes and gluatathionine peroxidase which protects rodents from oxidative damage, other studies have shown the opposite.
- CR has been shown to bolster the non-enzymatic antioxidant defenses such as increasing the levels of reduced glutathionine.
- it has been shown to enhance the ability to repair oxidatively damaged DNA and to replace damage proteins
what is the key thing that needs to be proved to give support to the CR via oxidative damage attenuation hypothesis? what is the evidence for this so far? (for=3) (against=2)
- does oxidative stress play a major role for oxidative damage in ageing
- flies selected for postponed senescence have an increased resistance to oxidative stress
- mice with a homozygous mutation in the p66Shc gene exhibit a markedly increased life span and an enhanced resistance to oxidative stress
- female mice heterozygous for IGF-1 mutant also showed increased resistance to oxidative stress.
mice deficient in superoxide disumatse have increased oxidative damage but o effect on life span or other age sensitive parameters. - the life span of long lived dros is not increased by the over-expression of antioxidants such as catalase
what is the altered glucose-insulin hypothesis?
- the fasting levels of plasma glucose and insulin are lower in rodent on CR but the rats on CR regime used glucose as fuel at the same rate per unit of metabolic mass as the control rats despite the lower plasma glucose levels and insulin plasma levels. This suggests that CR either increases glucose effectiveness of insulin responsiveness or both.
- CR has also been found to reduce plasma glucose levels rhesus monkeys. - of recent years the focuss has been on the insulin component of the glucose- insulin system- the major reason being that loss-of-functor mutations of the insulin signalling system result in life extension in c.elegands, d.melanogaster and mice.
