Exam 4 - Senescence Flashcards
What is the name of the last stage of development?
Senescence
Define senescence
Deterioration of the body leading to ‘natural’ death
List the 3 causes of senescence
- cell malfunction
- cell deterioration
- cell death
What do the cell repair/replacement VS. cell damage/death look like in children, adults, and senescence?
- children: replacement > death
- adult: replacement = death
- senescence: replacement < death
Changes that are visible on the outside of the body _________ what’s happening on the inside
mirror
What causes gray hair?
loss of stem cells -> no more melanocytes -> no more pigment
What causes skin to be leathery and cracked?
Collagen (which is like scar tissue) build up once elastin fibers are gone
What causes cataracts?
death of lens cells
What causes muscle atrophy?
The absence of myoblast and satellite cells
What causes osteoarthritis?
no more stem cells => no more chondrocytes => no more articular cartilage
What causes menopause?
no more oogonia which leads to no estrogen production
What causes atherosclerosis?
collagen replacing elastic and cholesterol replacing phospholipids. This results in oxidation which causes inflammation which causes swelling which ultimately results in a build up of scar tissue
What are two detrimental results of atherosclerosis?
- heart attack and failure due to coronary artery disease, which is caused by an increase in MAP from the reduced elasticity in the vessels as a result of scar tissue build up
- a stroke
What causes osteoporosis?
The number of osteoclasts in the body outnumbering the number of osteoblasts
What 3 things lead to hearing loss?
- “arthritis” of auditory ossicles (three middle ear bones)
- hardening of the eardrum
- graying of the hair cells in the cochlea
What is the result of slowed wound healing and immune response?
things like shingles or infections like influenza plus pneumonia
What causes type II diabetes in senescence?
Extra glucose is normally stored in adipocytes and adipocytes are created from stem cells. So once the stem cells run out you eventually run out of room for glucose storage
What type of damage occurs to the nervous system?
- decrease in fine motor skill ability
2. neurodegenerative diseases like Alzheimer’s and Parkinson’s
Why is cancer associated as a symptom of senescence?
Because as you age your risk for cancer increases
What is the primary reason that senescence occurs?
God’s curse to Adam and Eve. Sin => death
List three reasons WHY senescence happens
- mutation accumulation hypothesis
- antagonistic pleiotropy hypothesis
- disposable soma hypothesis
What is the mutation accumulation hypothesis
That random mutations due to environmental factors and DNA replication and repair errors accumulate and are passed on to daughter cells. This eventually leads to abundant cell death or cancer resulting in senescence
What is the antagonist pleiotropy hypothesis?
That a single gene is capable of producing various conflicting events. For example cells that used to promote reproduction can now cause death.
Give two examples of antagonist pleiotropy hypothesis
- testosterone = once produced secondary sex characteristics and supported sperm development, now can lead to prostate cancer developing
- Estrogen = once enhanced the immune system in order to support embryo, now can lead to an autoimmune disease
What is the disposable soma hypothesis?
That the genes that are selected for in natural selection are those which promote reproduction (stem cells that produce gametes) but that the genes used to maintain an old body that is no longer able to reproduce is a waste of energy and is therefore selected against.
How long did humans live prior to the flood?
around 1000 years
After Genesis 6 how long did people live?
Joseph lived 124 years, but since then no o1ne has lived more than 120 years.
What are the 6 proposed mechanisms to explain HOW senescence occurs?
- Accumulation of mutations of hypothesis
- Over-eating hypothesis
- Oxidative stress hypothesis
- Replicative arrest hypothesis
- Mitochondrial damage hypothesis
- Accumulation of senescent cells hypothesis
Accumulation of mutations of hypothesis
Especially mutations in DNA, RNA, and protein repair genes. The result can cell death, loss of function, and protein aggregation.
What neurodegenerative diseases are likely caused by accumulation of mutations?
Alzheimer’s,Parkinson’s, Werner’s, and Progeria
What gene has been studied in connection with mutations resulting in senescence?
WRN (named so because of Werner’s Syndrome)
What does the WRN gene code for?
It codes for a helicase which if mutated causes mutated proteins to be produced or it will limit the stem cell replication possible
What types of mutations result in Progeria?
mutations in DNA repair and insulin-signalling genes and organization within the nucleus
What type of mutation causes Progeria in children?
A mutation in the protein that lines the nucleus = lamin
Over-eating hypothesis
States that calorie restriction will increase longevity, this has shown to be true in experiments done on lab mice.
How does food limitation lead to an inability to reproduce.
When the body feels as though it is starving it spends its energy trying to stay alive and therefore does not want to waste money on attempting to reproduce. Therefore delayed/reduced menstruations will occur in order to focus on survival
Why are “starvation-avoidance” genes so important?
They have been found to be expressed under calorie restriction and have effects which are important in protection against senescence.
How would hormesis of calorie restriction provide protection against senescence?
By getting cells to get their guard up by introducing a slight stress of under eating
Oxidative stress hypothesis
ATP generation produces ROS as by products and the build up of these cause oxidatvie damage which alters protein function and breaks bonds which ultimately kills cells
Which enzymes protect against ROS?
superoxide dismutase, catalase, and peroxidase
Are anti-oxidants good for you?
Even though they have anti-oxidant activity they ultimately increase the risk of disease. So, no
Replicative arrest hypothesis
There are only two sources of replacement cells: (1) stable cells (2) adult stem cells. The problem is that stable cells have a limited ability and once they run out of division ability they become senescent which leads to senescent organs. And for various reasons stems cells also stop replicating
What types of cells are considered stable cells?
liver, kidney, and pancreas cells
How many times can stable cells divide?
50
Why is the division ability of stable cells limited?
They do not have telomerase, therefore after each replication the chromosomes become shorter and eventually the cell is not able to replicate.
What does the enzyme telomerase do?
It replaces chromosome tips after each replication, protecting the gene for indifferent replication.
What 2 types of cells contain telomerase?
- cancer cells
2. adult stem cells
What does the company life length promise?
To predict the biological age of a person and therefore the remaining lifetime left by analyzing the length of their chromosomes
What is GDF 11?
It is a growth factor gene that was found to maintain the ability for stem cells to continue replicating.
What was the heterochronic parabiosis experiment?
The circulation of a young mouse was attached to that of an old mouse. The researchers discovered that something in the blood (GDF 11) was increasing the longevity of the old mouse.
What is the next step to the heterochronic parabiosis experiment?
To insert a young persons blood into Alzheimer’s patient. Can possible halt neurodegenerative effects but won’t be able to repair damage that is already done
Mitochondiral damage hypothesis
mitochondrial mutation rate is much higher than nuclear genes and damaged mitochondria leads to a reduction in ATP production, also damaged mitochondria produce increased levels of ROS. If mitochondria become damaged beyond repair they induce cell suicide - neurodegeneration
Accumulation of senescent cells hypothesis
senescent cells cannot divide or function and they also induce chronic inflammation which we already know leads to cancer or heart diseases
What has been suggested as a counter to accumlaltion of senescent cells.
To use senolytic drugs in order to block the apoptosis inhibitor called BCl-2 so that those senescent cells will be killed
