HG exam 3 pgs 16-20
- Serotonin, norepinephrine deficiency
- Selective serotonin reuptake inhibitors allow more serotonin to stay the synapse
Schizophrenia
- Debilitating loss of ability to organize thoughts, perceptions, form of psychosis, delusions, hallucinations, voices giving instructions
- Genetic influences: Rare duplications, deletions Heritability 0.8____ Identical twin has it, you have 50% chance
- Environmental influences: Birth complications, Fetal oxygen deprivation, Viral infection at birth, Malnutrition, Mom – brain injury Living in cities, migration
Age begins = Males (17 - 27) Females (20 - 37)
Autism Spectrum Disorder
- Loss of communication and social skills (around 3 yo) & affects 1 out of 68 children (CDC 2014)
-5x higher in boys & 90% heritability
- 30 susceptibility or causative genes
- Proteins (gene products) and environment?
- Neurexins & Neuroligins are found in the pre & post synaptic neurons.
- Mutation causes misfolding, impairs signal
- 2 sets of synapses form during development:
1)those before birth___, 2) those in early childhood in response to ______experiances_________
Genetics of aging, longevity, & late onset disease
Maturing and aging
- Aging (definition) = the process of becoming older, in humans, aging represents the accumulation of changes in a human being over time
- Based on 3 perceptions
- 1.____chronological age___________ = based solely on the passage of time. Age in years. Limited significance in terms of health
- 2. ___biological age____________ = based on changes in the body (particularly physiological) that occur as people age
- 3. _____psychological age__________ = based on how people act and feel
Normal aging (AKA getting old sucks)
- cells____ – as cells age, function less. Genes control programmed cell death. Cells can only divide a limited number of times (telomeres)
- ___organs_____ – made of cells, when # of cells becomes too low, organ cannot function normally
- ____bones and joints___________– bones become less dense, weaker, prone to breaking, cartilage breaks down, ligament less elastic
- ____Muscles & Fat__________ – muscle mass & muscle strength decrease around age 30, lose fast twitch fibers, lose 15% muscle over adulthood. Body fat doubles by age 75.
- Eyes____ – lens stiffens (impairs focusing, after 40yo trouble with objects 2ft away), becomes dense (impairs light- 60yo needs 3x the light), yellows ( impairs color), reduced nerve cells (impairs depth perception), less fluid (feel dry)
- ears_– hard to hear high pitch sound, harder to understand letters (sound mumbled), more ear wax (ewwwww)
- ___mouth & nose____________– 50yo taste and smell diminish, nose gets bigger, dry mouth, taste buds less sensitive
- skin_____ – less collagen so tears easier, less neve endings, thinner, wrinkling, drier. Melanocytes decrease, brown spots
- ___Brain & nervous_____________ -# of nerve cells decreases, blood flow decreases, reaction and time to perform tasks slows, signal conduction decreases
- heart & blood_____________ – become stiffer, blood pressure increases, during exercise the heart cannot speed up as quickly or pump as fast
- lungs______ – muscles weaken, number of alveoli decreases, less oxygen absorbed,
less able to fight infection
- ___digestive_________ - less affected than other body parts, food moves through slower, can’t hold as much
- Kidneys_____ – becomes smaller, at 30yo filter blood less efficiently
- ____blood____ – bone marrow becomes less active , less blood to when needed
- ___immune system_____________ – immune cells act slowly, vaccines less effective, more infections, more cancer, less allergies
Adult-onset inherited disorders
- Genetic diseases that do not present until ___adulthood_________
- Due to
- 1)___inherited_______– Accumulation of gene products, Accumulation from birth gradually over decades, Genetic malfunction of substance that normally break them down
Example: Huntington disease
- 2)____acquired______ - Accumulation of harmful mutation, Some present at birth, most from exposure to mutagens, Mutations that activate dormant genes.
Example: Cancer
Adult-onset age related diseases
- Cancer
- Longer we live, more mutations__more mutations________ we accumulate
- We are living longer = increased cancer rates
- If you live long enough you will develop cancer
- Men: 1 in 2 risk developing (prostate cancer #1)
- Women: 1 in 3 risk developing (breast cancer #1)
- 10%___ of cancers are genetically inherited
Adult-onset age related diseases
- Diabetes
- 1 in 4 over 60 will develop diabetes
-Particularly Type 2 diabetes
- Insulin regulates glucose
- Cells resistant to insulin → little insulin → sugar builds up in bloodstream
- 73%_of developing diabetes is genetic, the remaining is contributed to age, race, obesity, inactivity, viral infections
- Type I diabetes has been associated with variants of the HLA genes__________ ( immune recognition self v non-self)
Adult-onset age related diseases
•COPD
- Chronic inflammation of airway = obstruction
- Emphysema & bronchitis
- 1% is genetic, the rest is environmental (smoking, particulate exposure)
Adult-onset age related diseases
Macular degeneration
- Leading cause of vision loss over age 50
- Macula____ breaks down = blurred vision in center
- Women 64% more likely develop AMD than men
- Genetics account for ____ age & environment account for rest
- 1 in 500 chance for 55-64 year olds
- Increases to 1 in 8 for 85+ year olds
- Those who work out 70% less likely to develop
- 89% of those with AMD are caucasian
Adult-onset age related diseases
- Alzheimer’s
- NOT a normal part of aging
- Early - onset (before age 60) - 3 genes
- 100% genetic
- Late - onset (after age 60) - not identified
- Early - onset almost 100%_____ genetic
Adult - onset age related diseases
- Immune dysfunction (Rheumatoid arthritis)
- Immune system attacks membrane in joints, pain, joint malformation
- not___ hereditary, genetics that affect immune function contribute
- Mutations in ___ HLA genes_______
- Environmental influences include hormones, occupational exposure to fibers, microbial infections, long term smoking & age
- underlying factor of all accelerated aging diseases = genomic instability
Hutchinson Gilford Syndrome
- Progressive disorder causes children to age rapidly (8x faster)
- Develop normally until 9 months – 2 years
- Average lifespan 13 years
- Lamin
- A = typically makes a protein for holding the nucleus together
- Mutation of Lamin A abnormal protein made = progerin ________
- Children develop aging diseases = arthritis, cataracts, cancer, hair loss, strokes
- Typically die of complication related to atherosclerosis
Werner syndrome
- “adult progeria” = develop normally until puberty
- Advanced aging around in 20’s
- Develop age related disorders = cataracts, type -2 diabetes, atherosclerosis, osteoporosis, cancer
- WRN gene = maintenance & repair of ____DNA ______
- Mutation = short nonfunctional protein, doesn’t reach nucleus to repair DNA
- Cells slow or stop dividing
Genes and longevity
- Average age of life expectancy
1960 2018
69.7_____U.S. 79.9____
___66.6____Men___76.6_____
___73.1____Women__81.4___
- Oldest living person ever: 122 years 164 days (Jeanne Calment, France, 1875 - 1997)
- Centenarians (100 years old): 1 in 6,000
- Supercentenarians (over 110 years old): 1 in 7 million
- On average people are living longer, but those passing the upper limits have dramatically plateaued.
- Genetic and environmental components
Genes and longevity - genetics
- Look at Centenarians (those that live to 100 ) and Supercentenarians (those that live to 110+)
- Mice = 2011, breast cancer drug ___tamoxifen__________ – reversed the symptoms of aging
- DNA damage & Telomeres
- Twin studies – genetics accounts for 20 - 30% of an individual’s chance of surviving to age 85
- Study found that centenarians have increase in
- 1) gene variants that confer ____disease reistance____________
- 2) gene variants that _____counteract_______ effects of disease associated genes ____chromosome II________– region shared among siblings that live to be 90+
Genes and longevity - genetics
- Single genes important for aging
- Insulin control
- Glucose metabolism
- Immune System function
- Cell cycle control
- Cholesterol metabolism
- Stress response
- Antioxidant production
- APOB & APOE = protein involved in metabolism of lipids
- ACE = controls blood pressure by regulating volume of fluids in the body
- HLA-DR = MHC class II cell surface receptor on T- cells
- SOD2 = enzyme that breaks down mitochondrial by - products
- TH = enzyme that helps make dopamine and norepinephrine and epinephrine Cytochrome P- 450 = metabolizes thousands of chemicals, found in mitochondria and ER
Environment and longevity
- ____diet, smoking, exercise________________ – determines how long & how well you age
- ____7th day adventist ___________ –encourage behavior that promotes healthy aging, live 8 years longer
than average US citizen (don’t smoke or drink alcohol, exercise regularly, vegetarian)
- ____calorie restriction___________
- 30% reduction in the amount of calories consumed
- Live 40% longer
- More resistant to age related diseases
- antioxidants_______= Reducing agents, limit oxidative damage by neutralizing free radicals Examples: Vitamin A, C, E, beta - carotene, dark chocolate, red wine
Telomere aging
- Shorten as we age
- Once they reach _____critical length________, cells either:
-Die off
- Enter ___senescence_________ = cells cease to divide - Human fibroblasts (50x)
- Hyper long telomeres in mice
- Kept the long length over time
- Less DNA damage___
- Better DNA repair___
- Fewer tumors ___
Oxidative stress
- Oxidative stress = imbalance between _______pro-oxidants & antioxidants________________
- ____free radicals________theory of aging = we age because cells accumulate free radical damage over time
- Free radicals = any molecule that has a single unpaird________ electron in outer shell
- Examples
- 1. Superoxide O2-