1
Q
Systems biology
A
- the systematic study of the interactions within biological systems
- with the goal to understand the entire processes within a biological system
2
Q
Emergent properties
A
- properties of an entire system that are not necessarily evident from examining each of the individual components
3
Q
Bioinformatics
A
- predicting the outcomes or responses in a living system using complex mathematical modelling
4
Q
Genomics
A
- the study of an organisms complete set of data
5
Q
Proteomics
A
- study of the set of all proteins produced within a biological unit
- this is typically an organ, an organ system or an entire organism
6
Q
Metabolomics
A
- the study of metabolites within a given unit
- cells, tissues, organs, organisms
7
Q
Reduction
A
- using isolated models (cells, organs, tissue)
- exquisite control over experimental conditions
8
Q
Integration
A
- integrated whole-body/organism approach
- less control over variables
- viewed as LESS mechanistic but MORE real world
9
Q
Example: Stimulation of fat oxidation in muscle by leptin
A
- lab data shows that leptin is good at burning fat
- this is done in the absence of many other hormones and factors
- in the entire body it is shown that the body can become leptin resistant and therefore is not a great fat burner
10
Q
Example: limits of maximal oxygen uptake
A
- whole body exercise - the more traditional integrated model
- cardiac output - the main limiter within this model
- single leg extensions - the reduction model, used to study effects in the absence of systematic changes
- muscle mitochondrial content - the main limiter within this model
11
Q
Clinical Example: regulation of blood glucose in type 2 diabetes
A
- current diagnosis is using a reductionist approach
- does not fully factor in time, location or context
12
Q
Nutritional Example: taking antioxidants
A
- arguments made for both
- yes; reactive oxygen species (ROS) can induce oxidative damage, promotes aging and diseases. antioxidants protect the cell from these damaging effects
- no; a certain amount of ROS are protective to the cells, they are a natural; signal involved in adaptation
- not enough context to decide If they are beneficial or harmful
13
Q
Genetic homology
A
- 98%+ similarity with chimpanzees
- 65% similarity with fruit flies
- incredible variation among individuals within the human species even though there is 9.9% similarity
14
Q
Control and Communication Network (CCN) components
A
- the CCN is made up of multiple components that interact and coordinate our functions
- the central nervous system; brain and spinal cord
- the peripheral nervous system; somatic nervous system and autonomic nervous system
- the endocrine system; endocrine tissue/glands and hormones
- the support and defence system; the immune system and beyond, support, movement, maintenance, repair, adaptation, defences
15
Q
CCN properties
A
- controls and coordinates the function of all physiological systems and organs
- the system is always on
- distributed throughout the entire body
- the network has redundancy; each component has multiple functions
- flows within the network via chemical-based, cell-cell communication
- the mind is not separate from the body and the 4 components are not separable
16
Q
CCN focus
A
- focal point of health in adult humans
- the integrator of inputs to health, disease and aging due to genetics, environment and lifestyle
- integrator of outputs to the 7 dimensions of health
17
Q
Aging and diseases within the CCN
A
- aging and diseases represent compromised function/structure of CCN
- many disease processes result from a diminished/abnormal function of the CCN (diabetes,cancer,depression, etc)
- there is a reduced function of the CCN with aging (impaired memory, Alzheimers, diminished touch sensitivity, etc)
18
Q
systems biology approach to healthcare
A
- systems biology integrated approach to health, disease and aging should enhance medical and healthcare practices
- basis of P4 medicine; personalized, predictive, preventative, participatory
- still challenges as a large amount of emphasis has been placed on genetics however susceptibility is determined by how genetics interact with lifestyle and enviornment
19
Q
Experimental models
A
- in silico; simulations with mathematics models (bioinformatics)
- in vitro; using Petrie dishes and test tubes
- ex vivo; isolated tissue/muscles
- animal models
- human participants
20
Q
In Vitro and Ex vivo examples
A
- isolated perfusion
- culturing cells
- isolated and incubated muscles
- transformed cells
- growing skin
21
Q
Nematodes and Fruit fly animal models
A
- used to study genetics
- Nematodes; 40% homology, easy to study and cheap, short life cycle, can be frozen and thawed, self-fertilized, transparent
- Nematodes examples; embryonic metabolism, fluorescent tagging to follow digestion
- Fruit Fly; 65% homology, very sensitive to environmental conditions,
- Fruit fly examples; neuropharmacology research
22
Q
Rat animal models
A
- very social and intelligent
- study lifestyle effects on metabolism
- researchers tend to take a more severe approach than they would with humans
23
Q
Mice animal models
A
- ease of applying recombinant DNA tech (knockout gene, over or under expression)
- test the importance of a single protein
- study lifestyle effects on metabolism
- cannot assume the effects of one rodent model onto another; rat data will not be the same as mouse data
24
Q
Swine animal models
A
- best non-primate model for human infant development and metabolism
- study organ transplant
25
Primates animal models
- closest model you can get to a human
- ethic and cost concerns
- study human pathologies, transplants, toxicology
26
Non-clinical human trials
- no medical treatment is given
- cannot predict or prove cause and effect; can only predict associations and correlations
- most commonly epidemiological studies
27
Clinical human trials
- definition; any investigation involving participants that evaluates the effects of one or more health- related interventions on health outcomes
- a medical treatment or placebo is given
- predicts a cause and effect
- double-blind, placebo-controlled clinical trials are the best
_ double blind; when the researchers and the participants don't know who has placebo vs medicine
28
Human clinical trial phases
- Preclinical; animal studies
- Phase 1 clinical trial; is the drug safe?, less than 100 people
- Phase 2 clinical trial; dosage, safety, 100s of people
- Phase 3 clinical trial; how does it compare to other treatments, 1000s of people
- After approval; assessment of long term use, benefits and risks
29
Cochrane reviews
- a database of systematic reviews and meta-analyses which summarize and interpret the results of medical research
30
New dimension of medicine; Evolutionary Medicine
- the application of modern evolutionary theory to understanding health and disease; our bodies have been shaped by evolutionary process
31
New dimension of medicine; Intergrative Medicine
- healing- oriented medicine that takes into account of the whole person, including all aspects of lifestyle
- emphasizes the therapeutic relationship between practitioner and patient
- makes use of all appropriate therapies
32
New dimension of medicine; Collective Medicine
- one health
- seeks to promote, improve and defend health and well-being of all species by enhancing cooperation and collaboration between physicians, vets and other scientific health professionals
33
New dimension of medicine; Enhancement Medicine
- treatments not needed for direct health
| - botox, viagra, liposuction, nootropics (brain enhancers)
34
Dimensions of time
- Trajectory, Rhythms, Homeostasis or Balance, Energy and information flow
35
Trajectory
- growth, development and aging
| - years, decades
36
Rhythms
- maintenance/repair, such as circadian rhythm, mentsrual cycle
days, weeks, months
37
Homeostasis or Balance
- maintenance or steady state
| - seconds, minutes, hours
38
Energy and information flow
- action potentials, enzymatic reactions
| - milliseconds, microseconds
39
Lifespan VS Healthspan
- lifespan; how long do I have to life (in Canada, 72yrs)
| - health span; how long will I be living a healthy, independent lifestyle (in Canada; 81yrs)
40
Biomarkers
- indicators of the biological state of the organism
| - find "things" to objectively measure, then we can track the aging/disease process
41
Shortening of height
- bone degradation, disk degeneration/compression
42
Loss of muscle mass
- Males; decrease in testosterone, IGF-1, inactivity
| - Females; inactivity and estrogen
43
Requirements of a biomarker
- reflect normal function or processes, or predict the risk of future development of disease
- have a predictable range across an identifiable category of individuals or must be routinely monitored over time
- have methods available for accurate and precise measurement
- normal ranges and diagnostic value if they are too high or too low
- change during the lifespan
- must be interpreted in relationship to age, sex and physiological state
- when you are outside the reference range for a biomarker, it may indicate risk for development of a disease, or the actual presence of a disease condition
44
New era of biomarkers
- networks within organs are perturbed during disease states
| - panels of blood markers provide assessment of perturbed networks and the organs
45
Biological rhythms
- Ultradain --> less than 24hrs (meals, cortisol)
- Circadian --> 24hrs (cortisol, sleep cycle)
- Infradian --> more than 24hrs (menstrual)
46
Circadian rhythms
- involved in almost all physiological processes
- controlled by peripheral clocks
- controls gene expression, regulation of enzyme activity, hormone secretion etc
- coordinate sleep, nutrient supply and activity patterns with metabolic patterns throughout the day
47
Disruption if circadian rhythm
- leads to a wide spread of health problems and premature aging
- elevated inflammatory cytokines
- gastrointestinal function
- obesity
- metabolic syndrome
48
Circadian rhythm in the brain
- in the suprachiasmatic nucleus
keeps time based on light signals from the retina
- nearly every cell in the body has a subsidiary clock that coordinates its metabolism with the rest of the body
49
Controlling the metabolic clock
- entrained by light/dark cycles
- involves melatonin; hormone produced by pineal gland
- blue spectrum light inhibits melatonin release
50
Disruption of circadian rhythm
- shift workers --> experience a greater risk of heart attacks, obesity, diabetes, cancer, Alzheimers
- late chronotypes (night owls) --> more likely to suffer from mental health
51
Example; circadian rhythm relevant to health
- risk of sudden heart attack is greatest mid-morning
- may be due to a protein called Klf15
combination of factors; caffeine, stress, fast food etc
52
Height as a biomarker
- osteoperosis
- criteria; loss of more than 2cm in one year
- there is a ~2cm daily variation in height
53
Limitations of using change in height as a biomarker
- varies during the day --> timing needs to be standardized
- needs to be measured over time
- low sensitivity
- doesn't directly precede or predict the disease state
54
Dual energy x-ray absorptiometry
- determine bone mineral density
55
Bone and plasma ca2+ homeostasis
- bone serves as a functional calcium store in the body
- acts as a buffer for plasma calcium levels
- plasma calcium must be maintained over a very narrow range
56
Loss of bone density
- men and women, have different bone densities and different patterns of bone loss as they age
- attain peak bone density between 20-30
57
Maximizing bone density
- consume sufficient calcium
- get adequate vitamin D
- participate in weight bearing physical activity most days of the week
- maintain a stable body mass that is not too thin
- get plenty of sleep
58
Direct intercellular communication; Gap junctions
- Connexons; subunits that form a channel, very small pore size, passage of sugars, amino acids, ions, found in all cells except mature skeletal muscle
- Intercalated disks; in cardiac muscle, allows for rapid and coordinated propagation of action potentials for rhythmic contractions, smaller than connexons, acutely regulated by phosphorylation/dephosporylation
59
Direct intercellular communication; membrane nanotubes
- formed from the plasma membrane
- longer than gap junctions and have a larger pore diameter
- transfer of nucleic acids or small organelles between cells
- way to transfer cellular components from stressed to healthy cells
60
Direct intercellular communication; Mechanosignal transduction
- conversion of mechanical stimuli into a cellular response
| - direct physical stress to the cells, eliciting a chemical or metabolic response
61
Examples; Mechanosignal transduction
- pulsatile and shearing stresses from blood flow on arterial endothelial cells
- mechanical stress to muscle fibres from weightlifting resulting in increases protein synthesis
- remodelling of bone and cartilage through physical stress
- conversion of pressure on skin into a neural impulse
- conversion of a soundwave into an electrical signal
62
Indirect intercellular communication; Chemical messengers
- paracrines, neurotransmitters, hormones
| - autocrine communication is also possible
63
Chemical messengers; Paracrine
- acting on a nearby cell
- "lock and key"
- examples; clotting factors, growth factors
- secreted hormones can act as a paracrine and can also act in an endocrine manner
64
Chemical messengers; Neurotransmitters
- synapse is a short distance
- axons can be long
- signal must be tightly controlled
- not too many molecules released
- need an auto shutoff
65
Chemical messengers; hormones
- can be water or lipid soluble
- must cross boundaries
- have target specificity; cells can express many different types of receptors, 100s or 1000s of a given receptor on a cell surface, the amount of a receptor is controllable
66
Hyrdophilic messengers
- water loving
- stored in secretory cells
- dissolve in plasma, don't need a carrier
- trouble crossing a lipid membrance
- secreted by fusing secretory vesicles to membrane and releasing
67
Hydrophilic messengers
- water hating or lipid loving
- storage is more limited, typically made on demand
- cannot dissolve in plasma; needs a carrier
- no trouble crossing a lipid membrane
BIOL 1080
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