Lecture 19 Flashcards
Why Do We Age
“It’s in our genes”
Genetic variation in ‘longevity’ genes
may influence lifespan
what are Single Nucleotide Polymorphisms (SNPs)
Each SNP represents a difference in a single DNA building block (nucleotide). They are responsible for human genetic variation
SNP frequency
10 million SNPs within the human population
– 1 every 300 nucleotides
Most frequent source for polymorphic changes
Not the only source of genetic variation
But represents major source that distinguishes one individual from another
Nutritional Genomics
certain factors can improve, impair or have no effect on ones performance. Eg. caffeine on athletic performance. metabolize slowly, quickly or moderately.
Nutritional Genomics cause
wide variability in nutritional data. some interventions work much better on some people or do not work at all
HapMap project is
a database that catalogues the 10 million SNPs
identified in the human genome
in hapmap database…
Genes are identified in green, SNPs are identified by blue lines. Number of SNPs in a single chromosome is so dense
that you have a solid blue bar.
Aging is associated with
an increase in inflammatory
cytokines that contribute to various age-related disorders
some examples of age related disorder
Alzheimer’s, cardiovascular disease, arthritis
Plasma levels of Interleukin-6 (IL-6) is an inflammatory cytokine is positively correlated with
greater mortality
SNP in the promoter* of IL-6 is associated with
increased IL-6 and
an increased mortality rate
Polymorphism:
a DNA sequence variation that is common in the population
a promoter is a
region of DNA that initiates transcription of a particular gene
Damage to the mitochondrial genome occurs
10x more frequently than the nuclear genome. Due to the generation of reactive oxygen species (ROS)
reactive oxygen species (ROS) are
Highly reactive chemical species containing oxygen
reactive oxygen species (ROS) examples
Peroxides
Superoxide
Hydroxyl radical
Singlet oxygen
DNA polymerase
gamma:
replicates and proof reads / repairs mitochondrial DNA
Accumulating mutations in mitochondrial DNA
accelerate
aging
Errors in replication become
more frequent as we age
With aging, DNA polymerase gamma
corrects errors less effectively
more apoptosis and reactive o2 species is a
side effect of aging
what does DNA polymerase gamma do
replicates and proof
reads / repairs mitochondrial DNA
in mice genetically engineered to carry
mutations in mitochondrial (mt) DNA
polymerase γ (gamma) the results are:
- mt DNA replication is error-prone
- Proof-reading activity is lost!
- Mice show accelerated signs of aging evident by 25 weeks (young
adult stage) weight loss, hair loss, curvature of spine; reduced lifespan
The mutated mice show a
Causative link between mtDNA mutations and aging phenotype
Can excersize reduce effects of aging?
yes, aging is Inevitable
But healthy aging can be influenced by
lifestyle choices
what is caloric Restriction
Generally refers to a 20 to 40% reduction in daily energy intake, but without malnutrition
Caloric restriction extended
healthy lifespan in rats, yeast, worms, fruit flies, mice, rabbits, dogs, and monkeys (no conclusive evidence in humans)
Study on how does EXERCISE compare to
drugs that are used to improve the
ability of muscle to respond to insulin
(i.e. insulin sensitivity)?
3234 diabetes-prone participants (diagnosed with prediabetes)
studied over 4 years
2 groups:
1) metformin (given as a preventative drug)
2) lifestyle modification
What were the lifestyle recommendations?
150 min per week of moderate exercise
Encouraged to follow Food Pyramid - this is a US study!
Target was to lose ~7% of initial body weight
findings of how does EXERCISE compare to
drugs that are used to improve the ability of muscle to respond to insulin (i.e. insulin sensitivity)?
Incidence of diabetes blunted the best by
lifestyle intervention. 31% with drug, 58% lifestyle reduction
