Studying Aging
What are the 3 research designs, and what do they mean?
1. Correlational - investigates relationships between two variables without experimental manipulation or control
2. Experimental - investigates relationships between variables after experimental control and manipulation (random assignment and assortment). This allows for a better answer to hypothesis and experimental findings. (looks for a cause-effect relationship)
3. Quasi-experimental - Also looks for cause-effet, but is in a situation that cannot use random assignment. Subjects are assigned to groups in non-random criteria.
Bonus: What are the 3 ways to evaluate a good study?
3 major regions of the brain. Give functions of each
Bonus: What are the lobes of the brain and what are their primary areas?
Bonus x 2: The cerebellum has a unique cell type in it. What is it, and what is it's function?
Give 3 examples of age-associated physical changes.
There's a lot
What are the phases of the cell cycle?
Interphase (G1, S, G2) and M phase.
What is SASP?
senescence-associated secretory phenotype. The senescent cell produces and secretes a variety of substances, such as inflammatory molecules, that can impact other cell and tissue. This can be beneficial in embryogensis or in response to a wound, but also associated with harmful effects as we age, such as chronic inflammation.
What are the 5 ways we define age?
Chronological age, biological age, mental age, maturity, social age
Parts of a neuron
Cell body (Soma), dendrites, axon, myelin sheath, terminal axon branches.
Bonus: Myelin sheath creates white matter. Unmyelinated neurons are grey matter. What part of the brain is a thin layer of grey matter that covers the brain?
What is the difference between primary and secondary aging?
Primary - normal, gradual, and inevitable. These changes occur to us as we age and are universal
Secondary - Pathological aging that is not considered a necessary and inevitable part of aging. Can be prevented or treated.
What are the external and internal signals that determine if a cell should progress through the cell cycle?
External Signals: Growth factors, nutrient availability, inhibitory signals from other cells (density-dependent inhibition)
Internal Signals: detection of DNA damage, whether duplication of DNA completed, size of cell, proper duplication of components and spindle assembly
What is the Hayflick limit, and how is it explained?
the number of cell divisions a cell can undergo before entering replicative senescence. This is different across tissues and organisms. This can be explained through telomere shortening or accumulate of DNA mutation
What are the 5 examples of model organisms? Give scientific names if possible
Yeast (S. Cerevisiae)
Worm (C. Elegans)
Fruit Fly (Drosophila Melanogaster)
Mouse (Mus Musculus)
Various Primates
Bonus: Give 3 characteristics of a good model organism?
What are the two talked about physical factors that are exhibited in Alzheimer's?
Bonus: There is a third, also popular factor. What is it?
What are 3 factors that influence aging? If possible, for each factor give something that can be done to counteract it.
- Genetics
- Genomic Instability (can be prevented by avoiding mutagens)
- Telomere Length
- Epigenetic Changes (can be prevented by avoiding environments which change genetic expression of aging factors)
- Cellular Senescence & Stem Cell Exhaustion (as a result of metabolic changes causing cell division, can be prevented with a low calorie or nutrient efficient diet)
- Other metabolic changes, such as in mitochondrial function or regulation of protein production and degredation
- Inflammation
- Changes to gut microbiome
- Altered Nutrient signaling and altered signaling between cells
- Environmental factors that include stress, lifestyle, exposure to pollution/toxins/radiation, medications
- Accidents, injuries, and infections
4 factors that influence cellular senescence.
replicative senescence, oxidative damage to DNA, cellular metabolism and caloric intake, and expression of CDK inhibitors.
Bonus: for each, give a biological mechanism that contributes towards senescence.
What is Reactive Oxygen Species (ROS)? What can they do? Give 3 specific results.
by-products of multiple cellular reactions, including those done in mitochondria. These can react and damage with DNA, proteins, and lipids throughout the cell. Buildup of ROS can lead to activating pathways in DNA Damage repair, apoptosis, and buildup of lipofuscin.
What are the Ferucci and WHO definitions of Frailty?
Ferucci - reduction of physiological compensation
WHO - frailty is a dynamic, age-related condition characterized by a decline in homeostatic reserves in multiple physiological systems that leads to decreased resistance and higher likeliehood to encounter adverse health outcomes
Bonus: What is the difference between Intrinsic Capacity and Vitality?
Bonus x 2: What is another name for Vitality?
What are the 3 main neurotransmitters we learned about? Give a function of each.
Dopamine, Acetylcholine, Serotonin.
Bonus: Each has a drug/general drug we learned about that is used to treat low levels of these transmitters. What are they?What are some disorders where aging is accelerated? What are their causes?
Progeria (mutation in Lamin A) and Werner Syndrome (mutation in WRN gene).
Bonus: What do those proteins/genes do?
What is IGF? When is it produced and what are it's effects (including signaling pathway)?
Insulin Growth Factor, produced when certain nutrient levels are reached and cause cell to progress through cell cycle.
IGF activates ERK and PI3K. ERK enters nucleus to turn on genes that regulate cell division. PI3K activates TOR, which removes inhibition of protein synthesis.
Bonus: What is stimulated when TOR signaling is low?
What is the Antagonistic Pleiotropy Theory and Evolutionary Cost and Benefit theory?
Antagonistic pleiotropy theory - natural selection favors genes that promote reproductive fitness early in life, which may be accompanied by unselected negative consequences later in life
Evolutionary Cost and Benefit Theory - theory implies that senescent cells have beneficial effects throughout life (for example, limiting tissue damage and suppressing tumorigenesis), but the cost of these effects overcomes the benefits in old age.
Name as many strategies that can be used to measure physical changes that occur during aging. What are their drawbacks?
- Measure the incidence rate of physical changes associated with natural aging (can be complicated if there is no agreement on what constitutes a particular condition)
- Measure the magnitude of physical changes that have occurred in individual
- Measure the incidence rate of aging-associated pathology/disease (diagnostic criteria varies and some cases may not be reported)
- Measure the magnitude of pathology-related change (how severe is it)
- Measure the impacts that natural or pathological aging have on function
- Measuring frailty (age related condition that results in decline of homeostatic reserves, leading to decreased resistance to stressors and increased risk of adverse health outcomes)
What 4 techniques can we use to study the brain structure/function?
Autopsies, fMRI, PET, and EEG.
Bonus: How do fMRI and PET scans work?Bonus x 2: Which one of the above is the best way of diagnosing people with Alzheimer's? How about those with seizures?
How does the gut microbiota can influence aging?
Changes in gut microbiota are associated with aging and can influence the function of the nervous system, the immune system, and the HPA axis.
How is DNA damage recognized? How does it's recognition lead to cell cycle arrest?
ATR recognizes single-stranded/unreplicated DNA.
ATM recognizes double-stranded breaks.
They both activate Chk1 and Chk2, which inhibit Cdc25, which are needed to activate Cdk1 and Cdk2. With no Cdk, there is no Cyclin-Cdk complex to progress through cell cycle.
Bonus: The above method causes arrest through lack of Cdk. There is another pathway that causes arrest through expression of CKIs. What is it?
What are the 5 characteristics of cellular senescence?
Morpholigical changes to nucleus or cell (abnormally enlarged and flat, with disproportionate increase in the cytoplasm-to-nucleus ratio)
Higher resistnace to apoptosis
Increased oxidative damage to cellular components
Changes to cell's metabolism (increased expression of SA-B-gal and build up of lipofuscin, a pigment composed of oxidized proteins and lipids)
SASP (senescence associateed secretory phenotypes)