MODULE 44

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Questions and Answers

What initiates the intrinsic apoptotic pathway?

Loss of membrane integrity

Binding of TNF-alpha to receptors

Release of cytochrome c from the mitochondria (correct)

Activation of caspase 8

Which caspase is activated first in the intrinsic pathway?

Caspase 9 (correct)

Caspase 14

Caspase 8

Caspase 3

Which molecular factors mediate the extrinsic apoptotic pathway?

Bcl-2 family members

Cytochrome c proteins

TNF-alpha and Fas ligand (correct)

IAP proteins

What is the role of executioner caspases in apoptosis?

To degrade cellular macromolecules Signup and view all the answers

What effect do pro-apoptotic Bcl-2 family members have on apoptosis?

They promote apoptosis Signup and view all the answers

Which of the following diseases is associated with decreased apoptosis?

Cancer Signup and view all the answers

What characterizes necrosis as a form of cell death?

It results from external factors like toxins and trauma Signup and view all the answers

Which of the following processes results from the action of caspases during apoptosis?

Membrane blebbing Signup and view all the answers

How do initiating caspases differ from executioner caspases in the apoptotic cascade?

They activate the executioner caspases Signup and view all the answers

What is the effect of the loss of the p53 tumor suppressor protein?

Decreased apoptosis Signup and view all the answers

What is a characteristic feature of senescent cells?

They express senescence-associated beta-galactosidase. Signup and view all the answers

What phenomenon is described by cells becoming senescent after a certain number of divisions?

Replicative senescence Signup and view all the answers

What typically increases the number of senescent cells?

Increased age Signup and view all the answers

Which of the following is a pro-tumorigenic effect of cellular senescence in older organisms?

Promotion of senescence-associated secretory phenotype (SESP) Signup and view all the answers

What is a result of telomere shortening during replicative senescence?

DNA damage responses activation Signup and view all the answers

Which process is characterized as programmed cell death?

Apoptosis Signup and view all the answers

What initiates the apoptotic process when the cell senses stress?

Intrinsic pathway Signup and view all the answers

What type of apoptosis involves external signals inducing the process?

Extrinsic Signup and view all the answers

What is the role of initiator caspases in apoptosis?

They start the caspase cascade. Signup and view all the answers

Senolytic therapy is proposed to improve health in older organisms by targeting which of the following?

Elimination of senescent cells Signup and view all the answers

What triggers the activation of caspase 9 in the intrinsic apoptotic pathway?

Release of cytochrome c from the mitochondria Signup and view all the answers

Which of the following accurately describes the role of the Bcl-2 family in apoptosis?

They can be both pro-apoptotic and anti-apoptotic factors. Signup and view all the answers

What is a consequence of excessive apoptosis?

Neurodegenerative diseases Signup and view all the answers

Which factor initiates the extrinsic pathway of apoptosis?

Fas ligand Signup and view all the answers

Which step in apoptosis is primarily responsible for the degradation of cellular macromolecules?

Executioner caspases action Signup and view all the answers

What is the role of caspase 8 in the apoptotic process?

It activates executioner caspases. Signup and view all the answers

Which of the following is commonly associated with insufficient apoptotic activity?

Cancer development Signup and view all the answers

Which event is NOT typically associated with apoptosis?

Inflammation and swelling Signup and view all the answers

What is primarily disrupted in necrosis compared to apoptosis?

Membrane integrity Signup and view all the answers

What type of signaling complex is formed during the extrinsic pathway of apoptosis?

Death-inducing signaling complex Signup and view all the answers

Which feature is associated with senescent cells?

Characteristic flattened appearance Signup and view all the answers

What term describes the limit to cell divisions before fibroblasts become senescent?

Hayflick limit Signup and view all the answers

What biological phenomenon contributes to senescence independent of telomere shortening?

Oncogene activation Signup and view all the answers

How does cellular senescence differ in younger versus older organisms?

It can be anti-tumorigenic in younger organisms and pro-tumorigenic in older ones. Signup and view all the answers

What is a characteristic of the senescence-associated secretory phenotype (SASP)?

Increased expression of inflammatory cytokines Signup and view all the answers

Which of the following describes the process of apoptosis?

Occurs as part of normal tissue homeostasis Signup and view all the answers

What triggers the intrinsic apoptotic pathway?

Oxidative damage and stress Signup and view all the answers

What is the outcome when caspases are activated during apoptosis?

Cell blebbing and nuclear fragmentation occur Signup and view all the answers

Which of the following pathways activates initiator caspases during apoptosis?

Intrinsic and extrinsic pathways Signup and view all the answers

What is the role of senolytic therapy?

To eliminate senescent cells to improve health Signup and view all the answers

What is the primary function of IAPs in the intrinsic pathway of apoptosis?

Inhibit the caspase cascade Signup and view all the answers

Which step occurs following the release of cytochrome c in the intrinsic apoptotic pathway?

Formation of the apoptosome Signup and view all the answers

What characterizes the activating factors involved in the extrinsic pathway of apoptosis?

Binding of pro-apoptotic ligands to specific receptors Signup and view all the answers

Which of the following best describes the action of executioner caspases in apoptosis?

They degrade cellular macromolecules Signup and view all the answers

What defines the relationship between the Bcl-2 family of proteins and apoptosis?

They can be both pro-apoptotic and anti-apoptotic Signup and view all the answers

Which outcome is associated with excessive apoptosis?

Neurodegenerative diseases Signup and view all the answers

What is the result of deregulated apoptosis in relation to diseases?

Excess apoptosis can cause autoimmune syndromes Signup and view all the answers

Which of the following statements best describes necrosis?

It is often caused by external factors such as toxins Signup and view all the answers

What is the primary difference between the intrinsic and extrinsic pathways of apoptosis?

Intrinsic pathway is mitochondrial-mediated Signup and view all the answers

What is a feature of senescent cells that distinguishes them from non-senescent cells?

They have a characteristic flattened appearance. Signup and view all the answers

Which mechanism is primarily responsible for replicative senescence in fibroblasts?

Telomere shortening. Signup and view all the answers

How does cellular senescence contribute to age-related diseases?

Through the senescence-associated secretory phenotype. Signup and view all the answers

What is the main difference in the role of cellular senescence between younger and older organisms?

It can become pro-tumorigenic in older organisms. Signup and view all the answers

What does apoptosis primarily involve during its execution phase?

Enzymatic degradation of cellular components. Signup and view all the answers

Which statement accurately describes senolytic therapy?

It targets and eliminates senescent cells. Signup and view all the answers

What is one consequence of deregulated apoptosis?

Inadequate tissue homeostasis. Signup and view all the answers

What feature is associated with the intrinsic pathway of apoptosis?

It leads to DNA fragmentation and cell blebbing. Signup and view all the answers

Which of the following is NOT a typical feature of apoptosis?

Loss of cell membrane integrity. Signup and view all the answers

What role do inflammatory cytokines play in senescent cells?

They contribute to the senescence-associated secretory phenotype. Signup and view all the answers

Study Notes

Cell Senescence and Death

Senescent cells are metabolically active but no longer divide.
They have an immunogenic phenotype and express senescence-associated beta-galactosidase (SABG).
Senescent cells are typically larger and flattened, with nuclei containing senescence-associated heterochromatin foci (SAHF).
Changes in gene expression and inflammatory cytokine expression are observed.
Fibroblasts in culture become senescent after ~50 divisions (Hayflick limit).
Replicative senescence results from telomere shortening and DNA damage responses.
Senescence can also result from oxidative damage, oncogene activation, or cell fusion.
Senescent cells increase with age.
Senescence may be an anti-cancer mechanism (anti-tumorigenic in younger organisms; pro-tumorigenic in older organisms).
Senescent cells can contribute to age-related diseases
Senolytic therapy aims to eliminate senescent cells to improve health and lifespan in older organisms (mice models).

Apoptosis

Apoptosis is programmed cell death, highly regulated and orderly.
Biochemical events include: cell blebbing, shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay.
Billions of human cells undergo apoptosis daily—part of normal tissue homeostasis.
Deregulated apoptosis can lead to disease (too much or too little apoptosis).
Two pathways trigger apoptosis:
- Intrinsic pathway (cell-stress induced): This involves the mitochondria.
- Extrinsic pathway (extracellular signals induced): TNF, Fas, and other factors.
Both pathways activate caspases; specific proteases. Initiator caspases start the cascade; executioner caspases perform the terminal steps.
Caspase-independent apoptosis occurs with apoptosis-inducing factor (AIF).

Apoptosis Pathways

Intrinsic pathway:
- Deactivates inhibitors of apoptosis (IAPs).
- Cytochrome c releases from mitochondria, forming apoptosome.
- Caspase-9 activates executioner caspase-3.
Extrinsic pathway:
- TNF or Fas ligand binds to receptors.
- Forms death-inducing signaling complexes (DISC), involving TRADD and FADD.
- Activation of caspase-8 leads to a cascade.

Caspase Cascade

Caspases initiate, and executioner caspases complete programmed cell death by degrading cellular macromolecules.

Apoptotic Disassembly

Visible process phases include membrane blebbing, nuclear fragmentation, protrusions, and cell fragmentation
Apoptotic process leads to the formation of apoptotic bodies.

Bcl-2 Family

Bcl-2 family proteins are modulators of apoptosis (pro-apoptotic or anti-apoptotic).
Associated w/ outer mitochondrial membrane and exert effects through mitochondria-mediated apoptosis.

Necrosis

Necrosis is a non-apoptotic cell death.
Triggered by external factors (infections, toxins, trauma).
Leads to loss of cell membrane integrity, DNA degradation, nucleus shrinkage, and fragmentation.
Harmful to the organism (can lead to inflammatory responses and tissue damage e.g. gangrene).

Apoptosis, Senescence, & Necrosis

Senescence, apoptosis, and necrosis all halt cell replication but differ in mechanisms and outcomes.
Senescent cells are metabolically active and retain a distinct phenotype.
Apoptosis is tightly controlled and can follow intrinsic or extrinsic pathways.
Necrosis is a detrimental, uncontrolled cell death pathway initiated by external stressors.

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Description

Test your knowledge on cell senescence and death, exploring the characteristics and implications of senescent cells. Delve into their role in aging, anti-cancer mechanisms, and the impact of senolytic therapies. This quiz will cover key concepts and processes related to cellular aging.