Senescence Flashcards
(53 cards)
aging is?
the inevitable time-dependent decline in physiological organ function that eventually leads to death
changes in life expectancy throughout human history
-changes in the environment, nutrition, and medical care –> can extend expected survival age
-the average age expectancy continues to increase
-the area under the curves has dramatically increased
the ______ lifespan appears to be unchanged?
maximum
central nervous system effects from aging
extreme shrinkage of the cerebral cortex
severely enlarged ventricles
shrinkage of hippocampus : learning and memory
respiratory system effects from aging
-clogged and deformed alveoli
(fewer and large)
timeline of ageing research
caloric restriction enhances lifespan in mice and rats (1930s)
The 1950s - medewar accumulation theory, Williams antagonistic pleiotropy
1960s- Hayflick limit
1990s- senescence observed in human aging
2000s- SASP identified: senescence-associated sensitive phenotype
, first senolytics clinical trial
9 hallmarks of aging, grouped into 3 categories
- the primary causes of cellular damage
-genomic instability
-telomere attrition
-epigenetic alteration
-loss of proteostasis - compensatory or antagonistic responses to the damages
-cellular senescence
-mitochondrial dysfunction
-deregulated nutrient sensing - the consequences of aging cues: hallmarks group 1-2
responsible for the functional decline associated with aging
-stem cell exhaustion
-altered intercellular communication
Alexis Carrel
studied phenomenon of senescence or aging
“on the permanent life of tissue outside of the organism”
-tissue from embryonic chicken heart, the cultures were supplied with nutrients regularly
-tissue were maintained for over 20 years– this is longer than a chicken’s normal lifespan
“all cells continued to grow indefinitely”- this was widely accepted in the 20th century
an image of a thirty-day-old culture of connective tissue. in the center there was debris of old plasma, around it is a ring of concentric layers of very active new tissue
primary cells
cells obtained from original tissue that have been cultivated in vitro for the first time
cell strains
cells were derived from animal tissue, sub-cultivated more than once in vitro (diploid)
cell lines
immortal cells that have been grown in vitro for extended periods of time (years) (heteroploid)
cultured normal human cells have a limited capacity to divide
-around 40-60 doubling before entering a senescence phase
cell alteration
phase 1: or primary culture: the beginning of culture. cells are isolated from the original tissue
-this phase terminates with the formation of the first confluent sheet
phase 2: the luxuriant growth period where cells are continuously proliferating
-cells in this phase are termed “cell strains”
- an alteration may occur at any time giving rise to a “cell line” -whose potential life is infinite
phase 3: the period where cell replication rate slows, a phenomenon named “senescence”
-cell strains enter phase 3 and are lost after a finite period of time
primary causes of cellular damage
genomic instability, telomere attrition, epigenetic alteration, loss of proteostasis
compensatory or antagonistic responses
cellular senescence or ageing
eukaryotic cell
10 to 100 um
-can see the nucleus
-condensed chromatin
-an extension of nuclear envelope
cytoplasm: fluid within the cell that surrounds the organelles
building blocks of life
DNA, RNA, and protein
liquid-liquid phase separation (LLPS)
-underlies the formation of membrane-less organelles (MLOs)
-LLPS leads to a conversion of homogenous solution into a dense phase and a dilute phase
-intrinsically disordered proteins (IDP’s) containing, LCDs, PLDs (PrLDs) etc bind to multivalent polymers such as RNA and DNA as well as proteins
-MLOs function to concentrate proteins, and nucleic acids, and regulate gene expression
nucleolus and paraspeckles are nuclear MLOS
stress granules (SGs), RNA transport granules, and P-bodies are cytoplasmic MLO’s
Paraspeckle is involved in?
gene expression regulation, RNA processing
stress granule is involved in?
translational regulation, antiviral defense, response to stresses, store some mRNA and proteins
Nucleolus is involved in?
ribosome biogenesis
cajal body is involved in?
pre-mRNA and pre-rRNA processing
the p body is involved in?
post-transcriptional modification, response to stress
nuclear pore complex?
nuclear import and export, tumor, immune
