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Questions and Answers
What is a characteristic feature of senescent cells?
What is a characteristic feature of senescent cells?
What is the Hayflick limit associated with cellular senescence?
What is the Hayflick limit associated with cellular senescence?
Which of the following factors can induce cellular senescence independently of telomere shortening?
Which of the following factors can induce cellular senescence independently of telomere shortening?
In which scenario is cellular senescence more likely to be pro-tumorigenic?
In which scenario is cellular senescence more likely to be pro-tumorigenic?
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What process describes the regulated, orderly death of cells?
What process describes the regulated, orderly death of cells?
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What are the two main pathways that initiate apoptosis?
What are the two main pathways that initiate apoptosis?
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Which molecule is released during intrinsic apoptosis to activate the caspase cascade?
Which molecule is released during intrinsic apoptosis to activate the caspase cascade?
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Which type of cell death may occur independently of the caspase pathway?
Which type of cell death may occur independently of the caspase pathway?
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What factors can initiate the extrinsic pathway of apoptosis?
What factors can initiate the extrinsic pathway of apoptosis?
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Which type of caspases are responsible for the degradation of cellular macromolecules leading to cell death?
Which type of caspases are responsible for the degradation of cellular macromolecules leading to cell death?
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What is the role of BCL-2 family proteins in the process of apoptosis?
What is the role of BCL-2 family proteins in the process of apoptosis?
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Which disease state is associated with reduced levels of apoptosis?
Which disease state is associated with reduced levels of apoptosis?
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What primarily distinguishes necrosis from apoptosis?
What primarily distinguishes necrosis from apoptosis?
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What is the primary difference between senescence and apoptosis?
What is the primary difference between senescence and apoptosis?
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How is apoptosis typically triggered?
How is apoptosis typically triggered?
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Which outcome is generally associated with excessive apoptosis?
Which outcome is generally associated with excessive apoptosis?
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What process is characterized by cells becoming larger and exhibiting a flattened appearance?
What process is characterized by cells becoming larger and exhibiting a flattened appearance?
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What leads to replicative senescence after approximately 50 divisions?
What leads to replicative senescence after approximately 50 divisions?
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What effect does senolytic therapy have on senescent cells?
What effect does senolytic therapy have on senescent cells?
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Which statement is true about apoptosis?
Which statement is true about apoptosis?
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What role do caspases play in the process of apoptosis?
What role do caspases play in the process of apoptosis?
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Which type of apoptosis is triggered by internal cellular stress?
Which type of apoptosis is triggered by internal cellular stress?
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What does the senescence-associated secretory phenotype (SASP) include?
What does the senescence-associated secretory phenotype (SASP) include?
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What initiates the 'caspase cascade' during apoptosis?
What initiates the 'caspase cascade' during apoptosis?
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In older organisms, what role can cellular senescence play?
In older organisms, what role can cellular senescence play?
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Which event is NOT typically associated with apoptosis?
Which event is NOT typically associated with apoptosis?
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What is the role of executioner caspases in apoptosis?
What is the role of executioner caspases in apoptosis?
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Which mechanism can lead to cell death through external factors such as toxins or trauma?
Which mechanism can lead to cell death through external factors such as toxins or trauma?
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What is a consequence of too little apoptosis in an organism?
What is a consequence of too little apoptosis in an organism?
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What type of proteins are the BCL-2 family members?
What type of proteins are the BCL-2 family members?
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Which of the following describes a primary outcome of apoptosis?
Which of the following describes a primary outcome of apoptosis?
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What characterizes the intrinsic pathway of apoptosis?
What characterizes the intrinsic pathway of apoptosis?
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Which statement accurately describes senescence?
Which statement accurately describes senescence?
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What is commonly observed in necrotic cell death?
What is commonly observed in necrotic cell death?
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What factor is crucial for the function of BCL-2 proteins?
What factor is crucial for the function of BCL-2 proteins?
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What triggers the activation of caspase 8 in the extrinsic pathway?
What triggers the activation of caspase 8 in the extrinsic pathway?
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Study Notes
Cellular Senescence
- Senescent cells do not divide but are metabolically active.
- They have an immunogenic phenotype.
- They express senescence-associated beta-galactosidase.
- Typically larger and flattened appearance.
- Nucleus has senescence-associated heterochromatin foci (SAHF).
- Changes in gene expression lead to senescence-associated secretory phenotype, including inflammatory cytokines.
Senescence Mechanisms and Consequences
- Replicative senescence occurs after approximately 50 cell divisions ("Hayflick limit").
- Telomere shortening and DNA damage responses contribute.
- Senescence can occur independently of telomere shortening, due to oxidative damage, oncogenes, or cell fusion
- Associated with age.
- In younger organisms, it is anti-tumorigenic, but may be pro-tumorigenic in older organisms.
- Senescent cell accumulation linked to age-related diseases.
- Senolytic therapy can kill senescent cells, improving health and lifespan in animal models.
Apoptosis: Introduction
- Programmed cell death; regulated and orderly process.
- Molecular/biochemical events include blebbing, shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay.
- Billions of human cells undergo apoptosis daily to maintain tissue homeostasis.
- Can be dysregulated in diseases (too little or too much).
- Two pathways: intrinsic (cell senses stress) and extrinsic (cell responds to outside signals).
- Both pathways utilize caspases (initiator and executioner).
- Caspase-independent apoptosis is also possible (e.g., apoptosis-inducing factor or AIF).
Basic Control of Apoptotic Pathways
-
Intrinsic Pathway:
- Deactivation of proteins that inhibit apoptosis (IAPs).
- Cytochrome C release from mitochondria, forming the apoptosome.
- Activation of caspase 9, then executioner caspase 3.
-
Extrinsic Pathway:
- TNF-alpha or Fas binding to cell surface receptors.
- Formation of death-inducing signaling complexes (DISC) with TRADD and FADD.
- Activation of caspase 8 (and other caspases).
Caspase Cascade
- Initiating and executioner caspases are involved in the intrinsic and extrinsic pathways; crucial in cell death.
- Initiating caspases activate executioner caspases.
- Executioner caspases degrade cellular components causing cell death.
BCL-2 Family of Apoptotic Factor Proteins
- Important modulators of apoptosis (either pro- or anti-apoptotic).
- BH domains crucial for pro- or anti-apoptotic function
- Located on the outer mitochondrial membrane.
- Involved in mitochondrial-mediated apoptosis.
Apoptosis and Disease
- Dysregulated apoptosis implicated in several diseases, including cancer, autoimmune disorders, neurodegenerative diseases, infections.
- Therapeutics aimed at promoting or suppressing apoptosis as needed.
Necrosis
- Non-apoptotic cell death, typically in response to external factors like injury, infection, or toxins.
- Characterized by loss of cell membrane integrity, DNA degradation, and cellular contents spilling out.
- Often inflammatory response and tissue damage.
Putting It Together
- Senescence, apoptosis, and necrosis all halt cell replication, but using different mechanisms.
- Senescence involves metabolically active cells that do not divide.
- Apoptosis is a tightly regulated programmed cell death.
- Necrosis is a harmful non-programmed cell death.
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Description
Explore the crucial concepts of cellular senescence, including the characteristics and mechanisms behind senescent cells. Understand the implications of replicative senescence on aging and age-related diseases, as well as potential therapies targeting these cells.
