BIOL 1080 Lecture Notes - Lecture 1: Vo2 Max, Systems Biology, Blood Sugar
2 May 2018
School
Department
Course
Professor
The systematic study of complex interactions in biological
systems
•
Exquisite control over experimental conditions
!
Can elucidate mechanisms
!
Isolated models (molecules, cells, organs, tissues):
○
Less control over variables
!
Viewed as less mechanistic (i.e. what factor was
the most important)
!
Integrated whole-body or organism approach:
○
Isolated test is done in the absence of other
hormones
!
Overweight individuals become leptin resistant
!
Different outcomes occur with reduction vs
integration experiments
!
Ex. Stimulation of fat oxidation in a muscle by the
antiobesity hormone, leptin:
○
Muscle mitochondrial content limits
VO2 max
!
Single leg extensions -reduction model
□
VO2 max is limited mainly by
cardiac output
!
Whole body exercise -integrated model
□
What limits maximal oxygen uptake?
!
But blood flow and neural input would no
longer be factors, so is it physiologically
relevant?
□
Examining mechanisms of fatigue in an
isolated, contracting muscle
!
Other examples:
○
Reduction vs. Integration
•
Incorporates many levels from genes to proteins to
tissues to integrated systems
○
Involves mathematical modeling and computational
power
○
Systems biology considers interactions and dynamics
•
Fasting blood glucose concentrations > 6.9mM
or OGTT result > 11.1mM (@ 2hrs)
!
Present diagnosis is a reductionist approach
○
Time -single time
!
Space/location -single site
!
Context -doesn’t tell you why blood glucose is
increased
!
Considerations:
○
If we don’t know why blood glucose is elevated, is it
logical to use a "one drug fits all" approach?
○
Clinical Example: Type 2 Diabetes and Regulation of Blood
Glucose
•
ROS can induce oxidative damage, promoting
aging and disease
!
Antioxidants protect the cell from damaging
effects
!
PROS
○
A certain amount of ROS is protective (leads to
apoptosis)
!
Some studies show that vitamin C/E
supplementation block mitochondrial
adaptations to exercise training
□
ROS are a natural signal involved in adaptation
(exercise training)
!
Trained induced increase in VO2 max
appears blunted by vitamin C in both
humans and rats
□
Training-improved endurance (in rats)
also appears to be blunted by vitamin C
□
PCG-1 (master switch that turns on
synthesis of mitochondria) is lower in
(rats) trained and vitamin C supplemented
individuals compared to untrained
□
Cytochrome C (component of the ETC) is
lower in trained with vitamin C
supplemented individuals compared to
trained (without supplements)
□
Oral administration of vitamin C decreases
muscle mitochondrial biogenesis and hampers
training-induced adaptations in endurance
performance
!
CONS
○
Nutritional Example: Taking Antioxidants
•
Systems Biology
Characteristics Reductionism Systems-Oriented
Perspective
Optimal Conditions where one
or few components
are responsible for the
overall behaviour of
the system
Conditions where
interactions between
components are
responsible for the
overall behaviour of the
system
Disease Types Acute, simple
diseases
Chronic, complex
diseases
Examples UTI Diabetes
Appendicitis Coronary Artery
Disease
Aortic Aneurysm Asthma
Theoretical
Limitations
Disregards
component-
component
interactions and
dynamics
Costly in resources and
time
Our emergent properties as an adult human makes us
unique (in spit of our remarkable genetic similarity to
other species
○
Our emergent properties produce incredible variation
among individuals within the human species (in spite
of 99.9% genetic homology)
○
Each human can be considered as an unique biological
system
1.
CNS -brain and spinal cord
○
PNS -somatic (voluntary) and autonomic
(involuntary) nervous system
○
Endocrine system -endocrine tissues and exocrine
glands; hormones
○
Support and Defense System -support, movement,
maintenance, repair, adaptation, defenses
○
The adult human biological system has a control and
communication network that coordinates the functions of the
person
2.
Controls and coordinates the function of all
physiological systems and individual organs
(including itself)
!
Its "always on"
!
It is distributed throughout the entire body
!
Each component of the network has multiple
functions and the network has redundancy
!
Information flow within the network is via
chemical-based, cell-cell communication
!
Properties of the control and communication network
are:
○
The CNN controls and processes information flow in the
adult human
3.
The CCN is the integrator of inputs to health, disease
and aging -genetics, environment and lifestyle
○
Spiritual
!
Physical
!
Mental
!
Social
!
Emotional
!
Environmental
!
Occupational
!
The CCN is the integrator of output to the 7
dimensions of health:
○
The CCN is the integrator of inputs and outputs of health in
the adult human
4.
Many disease processes result from a
diminished/abnormal function of the CCN
○
There is a reduced function of the CCN with aging
○
Aging and disease are processes which represent
compromised function/structure of the CCN
5.
What are the biological concepts of health from the systems
biology perspective of the adult human?
Introduction & Systems Biology
Monday,*September* 11,*2017
11:28*AM
Document Summary
The systematic study of complex interactions in biological systems. Viewed as less mechanistic (i. e. what factor was the most important) Stimulation of fat oxidation in a muscle by the antiobesity hormone, leptin: Isolated test is done in the absence of other hormones. Different outcomes occur with reduction vs integration experiments. Vo2 max is limited mainly by cardiac output. Examining mechanisms of fatigue in an isolated, contracting muscle. Incorporates many levels from genes to proteins to tissues to integrated systems. Clinical example: type 2 diabetes and regulation of blood. Fasting blood glucose concentrations > 6. 9mm or ogtt result > 11. 1mm (@ 2hrs) Context - doesn"t tell you why blood glucose is increased. Ros can induce oxidative damage, promoting aging and disease. A certain amount of ros is protective (leads to apoptosis) Ros are a natural signal involved in adaptation (exercise training) Some studies show that vitamin c/e supplementation block mitochondrial adaptations to exercise training.
