Lecture 19- Lifestyle, Aging, Disease Flashcards
Why do we age?
“It’s in our genes”
Genetic variation in ‘longevity’ genes
may influence lifespan
Is aging due to genetic variation?
Single Nucleotide Polymorphisms (SNPs)
* *Each SNP represents a difference in a single DNA building block (nucleotide)
-letter is snipped and this changes the genetic code and base pairs
* 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
-C binds to G A binds to T
What are nutritional genomics?
Exposure to nutrients changes our DNA replication, which leads to variations in our health or performance response
nutrient SNP leads to 3 genotypes
-Genotype 1: Improves athletic performance
-Genotype 2: No effect, no improvement of deteriotation or athletic capability
-Genotype 3: Impair: breaks molecules down slower
*complicates everything we know about our nutrition but in a good way
-some people respond some don’t
Are there a lot of genetic variation due to SNPs?
Yes an example is chromosome 10
-international HapMap project is a database that represents genetics in individuals
-1 in 300
-23 pairs of chromosomes 46 pairs in general
-SNP- change genetic variation
-*many variations within the genetic code because of SNP even though we are genetically identical
What links genotypes to mortality?
-one small location on the gene that contributes to longevity
* Aging is associated with an increase in inflammatory
cytokines (bile 6) that contribute to various age-related disorders
– Alzheimer’s, cardiovascular disease, arthritis
* Interleukin-6 (IL-6) is an inflammatory cytokine
-promotes inflammation in your body
– Plasma levels positively correlated with greater mortality
-as this gene increases so does greater mortality
* SNP in the promoter* of IL-6 is associated with 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
-SNP within promotor gene
-Negative Correlation: as levels increase the correlating factor’s risks decrease
-Ex: anti-inflammatory drugs reduce one’s risk of obesity
Do we age due to mitochondrial DNA damage?
yes!
* Your mitochondria contains genes, too!
* e.g. components of the electron transport chain
-ETC= cluster of proteins that transport electrons to drive the creation of ATP
* Damage to the mitochondrial genome occurs *10x more
frequently than the nuclear genome
* Due to the generation of reactive oxygen species (ROS)
* Highly reactive chemical species containing oxygen
Peroxides
-causes more oxidative stress in the body leading to damages cells which can lead to other health diseases such as cancer
Superoxide
Hydroxyl radical
Singlet oxygen
* Errors in replication become more frequent as we age :(
Accumulating mutations in mitochondrial DNA accelerates aging
-DNA replication needs the DNA polymerase gamma to work efficiently to minimize these numbers
DNA polymerase gamma: replicates and proofreads / repairs mitochondrial DNA
What is mitochondrial DNA damage and aging?
With aging, DNA polymerase gamma corrects errors less effectively :(
-error prone DNA Pol-gamma and decreases DNA repairs leads to DNA mutations that lead to apoptosis- leads to programmed cell death due to eliminating unwanted cells
-damaged mitochondrial proteins also leads to DNA mutations
-also leads to aging
How is the mouse genetic model for aging based on mitochondrial mutations?
Mice genetically engineered to carry mutations in mitochondrial (mt) DNA polymerase γ (gamma) leading to mitochondrial damage
*DNA polymerase gamma: replicates and proof reads / repairs mitochondrial DNA
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
These two mice are the same age!
*Causative link between mtDNA mutations and aging phenotype
Can exercise reduce the effects of aging?
PolG mice – lack mt DNA error correction and show increased mt DNA mutations and overall advanced aging
*randomized control trial
-positive outcome
DNA mutations: occurs more in sedentary mouse with gene rather than exercises mouse with gene
-Brain Weight: exercised mouse migates error
-wild type (regular mouse) is in between
-significant difference and increased levels between the exercised mouse and sedentary mouse
-sedentary lacks DNA correction
-Muscle Weight: no change between wild type and the exercised mouse
What influences healthy aging?
Healthy aging can be influenced by lifestyle choices!
-animal models do not always translate to the effect on humans
What is caloric restriction?
Generally refers to a 20 to 40% reduction in daily energy
intake, but without malnutrition
-massive drop makes it unethical in human studies
* Originally reported in 1935…severe food restriction
extended healthy lifespan in rats
* Demonstrated in yeast, worms, fruit flies, mice, rabbits, dogs, and monkeys
* No conclusive evidence in humans!
-uncertain caloric restriction if extends lifespan
What does drugs versus lifestyle entail?
How does EXERCISE compare to drugs that are used to improve the ability of muscle to respond to insulin
(i.e. insulin sensitivity)?
What does the New England journal of medicine state?
Preventing Diabetes: metformin or lifestyle modification?
-pre diabetes- blood sugar is not as elevated as type 2 diabetes and is considered reversible
* 3234 diabetes-prone participants (diagnosed with prediabetes) studied over 4 years- group based intervention
-started in the US moved to Canada
* 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
-diabetes prevention
What is the key finding of the new england journal of medicine?
Key finding: Incidence of diabetes blunted the best by
lifestyle intervention!!
Metformin is a Great drug 31% better than placebo
-reduces one’s risk of moving from pre-diabetes to type 2 diabetes
Lifestyle is an Incredible ‘drug’
-more affective in reducing this risk
-rare to see this is has almost double the affect
58% reduction in diabetes incidence vs placebo
What is the key takeaway?
Healthy aging can be influenced by lifestyle choices such as exercise and a healthy diet
