Terms and Concepts PDF

Lecture 17: - Type 2 Diabetes: is due to a particular gene or genes o Caused by a disfunction of cells not responding to the insulin in order to unlock these cells - Insulin: hormones that regulates the metabolism of glucose within tissues (glucose levels)...

Lecture 17: - Type 2 Diabetes: is due to a particular gene or genes o Caused by a disfunction of cells not responding to the insulin in order to unlock these cells - Insulin: hormones that regulates the metabolism of glucose within tissues (glucose levels) o Hormone produced by the pancreas o Insulin works like a key that unlocks the cells so the glucose can be stored in both the liver and muscles cells to be used as energy later on o Mechanism: 1. Functioning Beta cells in pancreas -> secretes insulin -> 2. Cells (muscle and liver) have to respond to the insulin to unlock them (cells) so that glucose can be taken out of the blood to decrease the blood glucose levels - Thrifty genotype hypothesis: proposer to explain rising rates of type 2 diabetes mellitus among some populations o Proposed by Neil in 1962 o Proposes the following… ▪ Type 2 diabetes is due to a particular gene or genes ▪ Critique: Many genes have a small additive effect ▪ Indigenous populations have a long history of experiencing periods of deaths and famine ▪ Critique: Application of hypothesis to Pacific Islands -> voyaging was hazardous Archaeological evidence -> voyages were frequent, well- planed and well provisioned, decreasing the risk of famine during these journeys  ▪ Indigenous populations have a higher frequency of gene(s) that are adaptive for surviving periodic famine (not only indigenous but all humans) The “thrifty” genotype inhibits the expression of insulin receptors so that glucose is stored in fat instead of used for fuel tissue metabolism Critique: o Lack of evidence for selective sweep (when a beneficial genotype is selected in a population and becomes very common and frequent in that population due to natural selection o Greater evidence for the genetic effects of founder effect - Leptin: a hormone that helps regulate your body’s weight by signaling your brain when you’re full, or feeling satiated - Genetic drift: when there are random changes in allele frequencies over time in a population due to random chance (luck) - Founder effect: special case of genetic drift which results in a reduction in allelic diversity due to chance and it occurs when a small population leaves or separates from a larger population and starts their own small population only bringing a small subset variation with them - Social determinants of health o Poverty o Lack of access to more health options of food o Lack of access to irrigation o Lack of land access Lecture18: - Thrifty phenotype hypothesis: o Undernutrition during gestation, infancy and childhood produces a biochemical signal that guides development processes which lead to a thrifty metabolic phenotype in adulthood o In other words, undernutrition during development leads to some change in metabolism in adulthood o Key Characteristics: ▪ Smaller body size (because early life nutrition leads to lower growth rates) ▪ Lower metabolic rate ▪ Lower fat oxidation (body is storing more fat) ▪ Greater fat deposition ▪ Increased cardo metabolic disease risk (diabetes, hypertension, etc) o Changes in epigenetic regulation of metabolism and growth are though to lead to the thrifty phenotype - Growth stunting: o Height for age z-score (HAZ) above the mean o If negative -> below the mean - Respiratory quotient (RQ): signifies whether the body is primarily metabolizing fat, carbohydrates or protein when fasted o Measured using indirect Calorimetry o RQ= VCO2/VO2  o RQ close to 1.0 -> carbohydrates metabolism o RQ close to 0.71 -> fat metabolism - Critical/sensitive period/window: when the development of infant/child is sensitive to environmental changes and have long lasting effects in adulthood - Evolutionary constraint o Argues that thrifty phenotype is due to evolutionary constraint and does not impact survival during under nutrition conditions o Argues that having a thrifty phenotype will not be beneficial for surviving a famine (whether the famine is during infancy, childhood or adulthood and we see these patterns because it is unavoidable because of how our bodies evolutionized o Argues that this pattern is not adaptive - Immediate Adaptive response hypothesis o “Making the best of a bad situation” scenario o The thrifty phenotype helps fetus/infant/child continue to develop in a low calorie environment, but comes with a cost to health across the life course o Adaption is not the same as health - Predictive Adaptive response hypothesis o Developmental cues are predictive of conditions in adults hood o Individual adjusts theirs phenotype during development in preparation for adult environment o Argues that the developing fetus, infant or child is changing their metabolism in preparation for an adult environment that has a high rush of famine or poor nutritional environment o Famine during pregnancy doesn’t necessarily predict risk of famine in child’s future o Poor early life nutrition impacts during development  ▪ Immune function ▪ Reproductive system ▪ Cognitive development o Limitation of this hypothesis: ▪ Early life poor nutrition has to be predictive of future famine ▪ Disease only arises when there is a mismatch between early life conditions and adult conditons Lecture 19: - Stress: the body’s physiological response to environmental challenges - or stressors - that strain an individual’s ability to maintain homeostasis and undermine adaptive capacity - Characteristics of the acute stress response o Rapid mobilization of energy from storage sites (like body fat) o Inhibition of future energy storage ▪ Blocking the breakdown and digestion of food o Increase in breathing rate, blood pressure and heart rate ▪ In order to transport nutrients and oxygen at a faster rate o Halt energy-expensive process ▪ Growth, reproduction, tissue repair - Autonomic nervous system: regulates unconscious bodily functions such as heart rate, blushing, goosebumps, digestion, etc o Sympathetic nervous system ▪ In charge of the “fight or flight” response ▪ Produces epinephrine (adrenaline) and norepinephrine Epinephrine: increases blood flow to the musicales and heart Norepinephrine: regulates blood flow through the blood vessels o Parasympathetic nervous system:  ▪ Turned off by stress ▪ Involves: Constriction of pupils Stimulates salivation Slows heartbeat Stimulates digestion Stimulates sexual arousal - HPA axis: Hypothalamus-Pituitary- Adrenal Axis o Brain processes psychical stress o Causes the hypothalamus to produce corticotropin releasing hormone (CRH) o CRH travels to the pituitary gland o Pituitary gland produces adrenocorticotropic hormones (ACTH) o ACTH travels to the adrenal glands o The adrenal produces glucocorticoids, such as cortisol o HPA affects different systems of the body - Cortisol (function and health effects) o Function: regulates body systems o effects many different system of the body - Evolutionary hypotheses for why stress makes us sick o Energy allocation model: the idea that the energy we consume and store in our body needs to be used for all these different processes for normal function ▪ Argues that chronic stress makes us sick because lots of energy is being allocated to our stress response to that psychosocial stress and less energy is available towards other processes like our immune system, repair muscle tissues, growth, reproduction, digestion, etc  o Acute vs. chronic stress ▪ For the majority of animals, stress is short-term crisis (acute stress) ▪ Humans chronically provoke the stress response e where we are chronically exposed to stress and for this reason we experience these negative affects (chronic stress) ▪ Characteristics of acute stress responses arre useful in running away from a predator but not useful in the context of chronic stress o Allostatic load: the wear and tear on the body and brain resulting from chronic activation of the psychological system involved in allostasis (rapid changes in physiology in response to an acute stressor) Lecture 20: - IBS (Irritable Bowel Syndrome): o Between 10-15% of adults in the US have IBS o IBS is associated with larger populations of Veillonella and Lactobacillus o Symptoms: ▪ Abdominal pain ▪ Constipation ▪ Diarrhea o Possible Causes: ▪ Stress ▪ Short-chain carbohydrates play a role Found in certain vegetables and fruits (broccoli and cauliflower) - Microbiota: the microbial organisms that live in our bodies o Ex: bacteria, viruses, fungi - Microbiome: the totality of microbes, their genetic information and the way in which they inert act - Taxa: a taxonomic group like species, genes or family o Taxon = plural for taxa - Factors that shape variation in microbiomes o Location on the body ▪ Taxonomic composition of microbiome depends on the anatomical location o Age o Acquisition during development ▪ Maternal microbiome characteristics and infant’s early environment will influences which taxa develop and how many taxa o Diet ▪ Diet composition can promote the growth of some taxa and hinder others ▪ Some gut microbes send signals to the brain that can influence craving for certain types of food o Antibiotics ▪ Dysbiotic: an in balance in taxa composition due to lower taxa diversity or missing key species o Microbes in the environment - Evolutionary hypotheses related to the gut microbiome o The composition of our microbiome today is likely different from the range of microbiome s that existed in our evolutionary past ▪ Contemporary U.S microbiomes are more lively to be in a state of dysbiosis due to a shift in diet and lifestyle (mismatch) ▪ Application of the evolutionary mismatch hypothesis The types and diversity of microbes we are exposed to today is different for our past The difference might underlie disease risk o During human evolution, hominins relied on their fut microbiome to provide extra calories from our good during periods of famine  ▪ Our microbes help us break down our food, make extra calories available and promoted fat storage ▪ This could be part of the reason why humans are more susceptible to obesity than other primates ▪ When we evolved as a species, we evolved… Energy expensive Brian’s Hunter-gatherer lifestyle A relationship with our microbes that promotes energy absorption and storage Today we have a mismatch o Fat-prompting relationship with out microbes in an environment where calories are plentiful Lecture 21: Why is childbirth so difficult? Why do so many women die during childbirth? - Obstetrical dilemma o Hominins began to show bipedalism behavior this caused a variety of changes to take place in the pelvis and lower limbs. The Pelvis became narrower as muscle groups changed their structure and position. The birth canal also changed in shape so that the entrance into the pelvic cavity was oriented differently than the exit. Because of this, babies couldn’t just slide straight out of the birth canal o the obstetrical dilemma says childbirth is hard becuase widening the pelvis to make birth easier would make it impossible for female humans to walk properly on both legs, however this is not true since it does not compromise the ability to walk on two legs. There hasn’t been a need to evolve wider hips yet. o problems arise when the babies head is too big to fit through the birth canal - Encephalization: an increase in the size of the brain relative to the rest of the body o this meant that newborn brains were also larger and these larger brains were enclosed by larger skulls which needed to fit through female hominins increasingly narrow pelvises o used to justify why medical interventions is necessary to save the lives of mothers and children o compared to the great apes that would rather like giving birth with no help, women seek a lot of health during childbirth o human babies are less developed than the babies of most of our close relatives ▪ Precocial: spices whose offsprings have some degree of maturity and mobility at birth (babies can open their eyes and hold on to their mother soon after birth) ▪ Altricial: species whose offspring are relatively more immature and helpless at birth - Stabilizing selection: for a particular trait, the population means trends toward the middle rather than one or both extremes o stabilizing selection should be acting on the female pelvis to keep that delicate balance between upright walking and large brains, however this is not the case since a study found that the female birth canal varies a lot. - Energetics of Gestation and Growth Hypothesis (EGG Hypothesis): suggests that pregnancy ends when the energy needs of the growing fetus exceeds the mother’s ability to meet those needs (baby could have grown too big)  o the trade-off that makes child birth so difficult might not be obstetric dilemma but the EGG hypothesis. However, both of these traits and more may play a role in the complicated process of childbirth Lecture 22: - Innate immunity o Defenses that don’t depend on prior exposure to the disease o Evolved before the adaptive immunity system o Represent the body’s first line of defense against infection and injury o Examples of components of innate immunity: ▪ Muscosal membranes ▪ Antimicrobial soluble proteins in blood, saliva and tears ▪ Phagocytic cells ▪ Inflammatory response - Inflammation o Part of the innate system o Responds quickly o Non-specific ▪ Triggered by external factors Examples: viruses, bacteria, allergens ▪ Triggered by internal factors Examples: cell damage from stress - Adaptive immunity o Also known as acquired or specific immunity o Depends on prior exposure to an antigen o Antigen: a substance that elicits a specific immune response ▪ Most pathogens (i.e bacteria, viruses, parasites) are composed of multiple distinct antigens o Defining features: ▪ Specificity  ▪ Diversity ▪ Memory o Examples of components of adaptive immunity ▪ T lymphocytes (such as killer T cells) ▪ B lymphocytes - Hygiene hypothesis o All living things evolved with a suite of parasites ▪ Humans have always had worms o Infancy and childhood -> maturing immune system learns how to respond to parasites o Improvements in hygiene and antibiotics -> fewer infections -> immune system doesn’t “learn” what is pathogenic _. Immune system attacks the body o Example f testing the Hygiene Hypothesis: Treating Crohns’ Disease with Worms – ▪ T cells (T lymphocytes) A type of white blood cell There are various types of T-cells o Killer T cells ▪ Directly kills virus-infected cells o Helper T-cells ▪ Determine if and how other parts of the immune system should respond to a specific, perceived threat ▪ Two types of Helper T-cells Th-1: concerned with virus and bacteria Th-2: concerned with infections by worms and other large parasites o Activating Th-1 -> Trains response of Th-2  o Activating Th-2 -> Trains response of Th-1 - Schistomiasis o Caused by parasitic flatworms (schistosomes) o Causes pain, malnutrition, anemia and diarrhea o In the long term can cause kidney and liver damage, growth stunting in children o places with more schistosomes have lower rates of autoimmune diseases - Immunomodulation: o The presence of schistosomes lead to immunomodulation (the regulation and modulation of immunity that might be achieved by reducing or enhancing the immune response) - WHO’s policy towards worms o Old policy ▪ Eliminate all worms ▪ Count the number of people without worms o New policy ▪ Reduce the number of worms per person ▪ Count the reduction in infection intensity ▪ Controversy Lecture 23: - GnRH: Gonadotropin-releasing hormone - LH: Luteinizing hormone - FSH: Follicular stimulating hormone - Estrogen ▪ an example of a form of estrogen is estradiol - Progesterone: plays a role in menstrual cycle, pregnancy and other aspects of reproductive system - How these hormones change across the menstrual cycle: reproductive hormones fluctuate across the menstrual cycle ▪ Luteinizing hormone (LH) is seen the highest during Ovulation ▪ Progesterone is seen the highest in the Luteal Phase ▪ Follicular stimulating hormone (FSH) seen the highest during the Ovulation ▪ Estrogen is the highest in the Follicular Phase - Follicular phase: follicles are maturing. (Days 1-12) ▪ FSH stimulates growth and maturation of ovarian follicle (cellular envelope that surrounds and nourishes the developing egg ▪ Rising levels of estrogen promotes the growth of the endometrium (uterine lining) - Luteal phase: follicle becomes corpus luteum, which produces progesterone. (Days 16-28) ▪ Endometrium prepares for implantation of blastocyte. ▪ Falling levels of estrogen and progesterone cause endometrium to shrink - Due to diminishing blood flow to endometrial cells - Invasion of endometrium by leukocytes which break down cells. - Evolutionary hypotheses to explain why we menstruate: 1. Maintaining the endometrium costs a lot of energy. - Strassman (1999) argues that shedding the uterine lining and regrowing it costs less energy than maintain it across the cycle. 2. Pathogen removal.  - Menstruation allows the female reproductive tract to remove pathogens that are associated with sperm (associated with sex) - Studies do not find that pathogen load is lower after menstruation. 3. Defective embryo removal - Many human embryos carry chromosomal abnormalities that make them non-viable. - Menstruation promptly gets the body ready for the next ovulation. 4. A signal of fertility - Sends a signal that cycling has resumed after a previous pregnancy. - However, many women experience menstrual cycles when they have a low probability of becoming pregnant. For example, shortly after puberty at the beginning of the reproductive years. - The relationship between # of menstrual cycles and cancer: ▪ A greater number of menstrual cycles are associated with higher risk of breast, ovarian and uterine cancer. ▪ Cancer risk is associated with: - Earlier age of menarche - Later age of first reproduction - Lower number of offspring ▪ Ovulation involves an increase in inflammation of ovaries. - Occurs during Days 13-15 of menstrual cycle ▪ Menstruation involves inflammation of the uterus. ▪ Estrogen causes changes in breast cellular growth across the cycle. ▪ There is some evidence that oral contraceptive reduces the risk of ovarian and endometrial cancers but not breast cancer. Lecture 24: Cancer: territorial expansion of a mutant clone - Subclone: a clone of a cell that has mutation. - Evolution of cancerous cells: ▪ Evolutionary principals can be applied to trace back in time and determine when the cancerous cells first originated. ▪ Important for discoveries related to early treatment/prevention. - Clonal sweep: when a subclone outcomes its neighboring cells, leading to an increase in the number of cells with the mutation(s) - Apoptosis: ▪ Programmed cell death. ▪ Innate immune system (in particular, inflammatory response) play a big role. - Application of mismatch hypothesis to cancer: ▪ Diet and physical activity patterns in the US are very different from our evolutionary past. Increased risk of positive energy balance. ▪ Association between long-term positive energy balance (i.e., obesity) and risk of breast, prostate, colon, and pancreatic cancer. But why? - More energy available for hormone production? - Link between obesity, inflammation, and cancer. ▪ Energy throughout Total number of calories consumed and burned. ▪ Greater access to energy -> larger energy budget -> greater total energy expenditure -> more reactive oxygen species (ROS) ROS - Produced as byproduct of mitochondrial metabolism. - Cause cellular damage, dysfunction of cells, cellular death, physiological decline. - Grandmother hypothesis: ▪ Grandmother’s productivity increased inclusive fitness and led to selection for increase lifespan. ▪ The grandmother plays a role in the care of the grandchild. - Embodied capital hypothesis: argues that these factors (listed below) likely evolved at the same time. They co-evolved in response to a dietary shift. ▪ Compared to other apes, humans have: Extreme brain size Prolonged childhood/juvenile period Intergenerational transfers Long life span - Active grandparent hypothesis: ▪ A hypothesis that attempts to answer, “why does physical activity, especially in middle-age, promote health?” ▪ Argues that selection for increased physical activity (PA) in humans was linked to selection for extended lifespans. ▪ The “stress” of PA stimulates investments in somatic repair and bodily maintenance that are less active in the absence of PA. Examples of PA’s effect on body repair/maintenance - Production of antioxidants - Reducing inflammation - Stimulating the parasympathetic nervous system to “turn off” the sympathetic nervous system. - Promote bone density. - Increase in mitochondria and glucose transporters. ▪ Health effects of physical activity 150 min/wk. of moderate exercise reduces a sedentary person’s relative risk of all-cause mortality by ~50%  Dose-dependent relationship between PA and breast and colon cancer - 3 to 4 hr. of moderate exercise/wk. -> o Reduce risk of breast cancer by 30-40% in women o Reduce risk of colon cancer by 40-50% in men and women PA stimulates the expression of tumor suppressor genes. PA helps the immune system attack mutant cells. ▪ Is this hypothesis an example of the “spandrel”? Spandrel - The triangular area between two adjacent arches and the ceiling they support. - A metaphor traits that have arisen as a byproduct and other adaptations.