Cell Aging Mechanisms and Factors
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Questions and Answers

What characterizes necrosis as compared to apoptosis?

  • Occurs primarily in a controlled manner
  • Always results in cell shrinking
  • Involves the destruction of many cells at once (correct)
  • Does not cause inflammation

Which nuclear change is characterized by the dissolution of the nucleus?

  • Pyknosis
  • Karyolysis (correct)
  • Karyorrhexis
  • Chromatin fragmentation

In which type of cell death does inflammation typically occur?

  • Cellular atrophy
  • Apoptosis
  • Necrosis (correct)
  • Senescence

Which statement is true about the process of apoptosis?

<p>Involves caspase dependent pathways (C)</p> Signup and view all the answers

What occurs to the plasma membrane during necrosis?

<p>It becomes disrupted (A)</p> Signup and view all the answers

Which of the following describes the cellular appearance during necrosis?

<p>Cells swell and burst (D)</p> Signup and view all the answers

Which characteristic is present in necrosis but absent in apoptosis?

<p>Cellular contents are released (D)</p> Signup and view all the answers

What visual characteristic might be noted in cells undergoing necrosis under a histological examination?

<p>Eosinophilia cell-like presence (A)</p> Signup and view all the answers

What condition arises when the body cannot combat excessive oxidation?

<p>Oxidative stress (A)</p> Signup and view all the answers

What is the role of antioxidants in the body?

<p>To delay or inhibit oxidative damage (C)</p> Signup and view all the answers

Which antioxidant vitamin is fat-soluble and prevents lipid peroxidation?

<p>Vitamin E (C)</p> Signup and view all the answers

What process describes the nonenzymatic linkage of glucose to molecules such as proteins?

<p>Glycation (C)</p> Signup and view all the answers

What are Advanced Glycation End Products (AGEs)?

<p>Glycated proteins or lipids exposed to sugars (A)</p> Signup and view all the answers

Which antioxidant is known to be water-soluble and reacts with various radical species?

<p>Vitamin C (B)</p> Signup and view all the answers

Which enzyme converts superoxide radical to hydrogen peroxide?

<p>Superoxide dismutase (SOD) (D)</p> Signup and view all the answers

What effect does aging have on the skin's antioxidant defense system?

<p>It weakens the system, reducing capacity to combat oxidative stress (D)</p> Signup and view all the answers

What is the role of the p53 protein in programmed cell death?

<p>It activates transcription of genes encoding proapoptotic proteins. (D)</p> Signup and view all the answers

Which initiator caspase is involved in the extrinsic pathway of apoptosis?

<p>Caspase 8 (C)</p> Signup and view all the answers

What triggers autophagic cell death?

<p>Pathogen invasion and stress conditions (B)</p> Signup and view all the answers

Which type of autophagy involves the formation of an autophagosome?

<p>Macroautophagy (A)</p> Signup and view all the answers

Which process does not involve the activation of caspases?

<p>Autophagic cell death (A)</p> Signup and view all the answers

How does microautophagy differ from macroautophagy?

<p>Microautophagy directly engulfs the cytoplasm via lysosomal membrane invagination. (A)</p> Signup and view all the answers

What is a characteristic outcome of necrosis?

<p>Cell swelling and bursting (C)</p> Signup and view all the answers

Which of the following is a component required for chaperone-mediated autophagy?

<p>Chaperone proteins (B)</p> Signup and view all the answers

What is a primary cause of replicative senescence in cells?

<p>Shortening of telomeres (A)</p> Signup and view all the answers

What is the Hayflick limit?

<p>The maximum number of times a cell can divide (C)</p> Signup and view all the answers

Which cells typically do not have active telomerase?

<p>Somatic cells (C)</p> Signup and view all the answers

What role do AGEs play in the aging process?

<p>They accumulate in structural proteins (D)</p> Signup and view all the answers

How are telomeres affected by cell division?

<p>They shorten with each cell division (C)</p> Signup and view all the answers

What is the primary consequence of irreparable DNA damage in cells?

<p>Cellular senescence or cell death (D)</p> Signup and view all the answers

What is lipofuscin associated with?

<p>Accumulation of aging cellular substances (C)</p> Signup and view all the answers

How do external environmental factors accelerate cellular aging?

<p>By damaging cellular components (A)</p> Signup and view all the answers

Which statement is true about telomerase?

<p>It helps maintain telomere length in specific cell types (B)</p> Signup and view all the answers

What defines a free radical?

<p>A molecule containing an unpaired electron (B)</p> Signup and view all the answers

Which of the following statements about cellular senescence is correct?

<p>It signifies a halt to cell division after a certain point (A)</p> Signup and view all the answers

What is the main role of the proteasome in the cell?

<p>Degrading damaged proteins (D)</p> Signup and view all the answers

What occurs when there is an excess of free radicals in the body?

<p>Oxidative stress develops (D)</p> Signup and view all the answers

Which of the following is NOT a source of free radicals?

<p>Essential nutrients (B)</p> Signup and view all the answers

What does oxidation involve when a free radical interacts with another molecule?

<p>Stealing electrons from the molecule (B)</p> Signup and view all the answers

What is the overall result of the imbalance between generation and disposal of by-products of cellular metabolism?

<p>Increased rate of DNA damage (A)</p> Signup and view all the answers

What is the role of caspases in programmed cell death?

<p>They cleave target proteins to instigate apoptosis. (D)</p> Signup and view all the answers

Which statement describes the intrinsic pathway of apoptosis?

<p>It can be triggered by internal cell damage or stress. (A)</p> Signup and view all the answers

How are procaspases activated?

<p>By cleavage at specific aspartic acids by other caspases. (C)</p> Signup and view all the answers

What triggers the extrinsic pathway of apoptosis?

<p>Binding of extracellular signal proteins to death receptors. (C)</p> Signup and view all the answers

What is the function of cytochrome c in the intrinsic pathway?

<p>To form an apoptosome with Apaf1. (A)</p> Signup and view all the answers

What is a key characteristic of death receptors?

<p>They contain both an extracellular and intracellular domain. (B)</p> Signup and view all the answers

Which component is primarily involved in the activation of downstream executioner procaspases?

<p>Activated initiator procaspase-9 from the apoptosome. (B)</p> Signup and view all the answers

What distinguishes the activation of initiator caspases from executioner caspases?

<p>Initiator caspases start the activation cascade. (D)</p> Signup and view all the answers

Flashcards

Oxidative stress

A process where free radicals, unstable molecules, damage cells and tissues.

Antioxidants

Molecules that protect cells from damage caused by free radicals.

Glycation

A natural process where sugars bind to proteins, lipids, or nucleic acids, leading to aging.

What are antioxidants?

Substances that can neutralize free radicals by donating an electron or hydrogen atom.

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Antioxidant enzymes

The body's natural defense against oxidative stress. They convert harmful free radicals into harmless forms.

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Superoxide dismutase (SOD)

An enzyme involved in the conversion of superoxide radicals to hydrogen peroxide. It's a key component of the body's antioxidant defense system.

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Catalase

Enzymes that catalyze the breakdown of hydrogen peroxide into water and oxygen. Another essential part of the antioxidant defense system.

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Antioxidant vitamins

Substances like vitamins E, C, and A that neutralize free radicals by donating an electron.

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Cell lysis

The rupture of cells and leakage of their contents into surrounding tissues.

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Inflammation

A non-specific immune response triggered by cell lysis, characterized by redness, swelling, heat, and pain.

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Pyknosis

A process where the nucleus of a cell condenses and shrinks.

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Karyorrhexis

A process where the nucleus of a cell breaks into fragments.

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Karyolysis

A process where the nucleus of a cell dissolves completely.

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Necrosis

A type of cell death that is unplanned, involves many cells, and is usually a result of injury or disease.

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Apoptosis

A type of cell death that is programmed, involves a single cell, and is often a part of normal development.

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Caspases

A family of enzymes that play a critical role in apoptosis.

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DNA damage and aging

DNA damage can lead to replication arrest, eventually causing cellular senescence (aging) or cell death.

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Environmental insults and aging

Environmental factors like radiation, toxins, and oxidative stress damage cellular components, accelerating aging.

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Free radicals

Free radicals are molecules with an unpaired electron, making them highly reactive and damaging to cells.

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Proteasome and aging

The proteasome is a cellular machinery responsible for degrading damaged proteins. Its decline with age leads to protein buildup, further worsening cell function.

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Sources of free radicals

The body naturally produces free radicals, but external sources like sun exposure, pollution, and smoking can also contribute.

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Oxidative stress and aging

Oxidative stress is a major contributor to aging and disease.

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Extrinsic Pathway of Apoptosis

A pathway of apoptosis triggered by external signals, such as death ligands binding to death receptors on the cell surface.

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Intrinsic Pathway of Apoptosis

A pathway of apoptosis initiated by internal signals, such as DNA damage or mitochondrial dysfunction.

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Autophagy

A type of programmed cell death where the cell consumes its own contents through a process of engulfment and breakdown.

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Macroautophagy

A form of autophagy where a membrane isolates and engulfs portions of cytoplasm, forming autophagosomes that fuse with lysosomes for breakdown.

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Microautophagy

A form of autophagy where the lysosome directly engulfs small portions of cytoplasm through inward folding of its membrane.

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Chaperone-Mediated Autophagy (CMA)

A form of autophagy where specific proteins are directly transported into lysosomes for degradation with the help of chaperone proteins.

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Eat me signal

In healthy cells, phosphatidylserine is only found on the inside of the cell membrane. When a cell is about to die, it flips to the outside, acting as a signal for other cells to clean up the dying cell. This is like a 'suicide note' for the cell.

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Caspase Cascade

Caspases are first made as inactive proteins called procaspases. Once the cell decides to die, other caspases activate the procaspases by cutting them. This sets off a chain reaction, activating more and more caspases until the cell is broken down.

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DISC

A complex of proteins that forms when death receptors are activated. It signals the start of the extrinsic pathway of apoptosis.

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FADD

A protein that binds to death receptors and helps initiate the extrinsic pathway of apoptosis.

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Cytochrome c

A protein released from mitochondria during the intrinsic pathway of apoptosis. It activates a caspase-activating complex called the apoptosome.

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Replicative Senescence

A natural process where cells stop dividing after a certain number of divisions caused by shortening of telomeres, the protective caps at the ends of chromosomes.

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Telomeres

The protective caps at the ends of chromosomes that shorten with each cell division.

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Telomerase

The enzyme responsible for rebuilding telomeres and restoring cell division. It is active in stem cells and germ cells but absent in regular body cells.

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Hayflick Limit

The limit to the number of times a cell can divide before it stops due to telomere shortening.

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AGEs (Advanced Glycation End Products)

Accumulated damage in cells due to aging, including glycated proteins and damaged organelles, which become resistant to degradation.

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Lipofuscin

A product of lysosomes containing enzymes for degrading proteins, lipids, and damaged organelles. This can accumulate in older cells.

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Telomere Maintenance in Germ Cells

When telomerase is active, it continuously rebuilds telomeres, ensuring the cells have an eternal lifespan. This is the case in germ cells.

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Feedback Loop of Damaged Proteins

A feedback loop where reduced activity of the proteasome (protein degrading machinery) leads to more damaged proteins, which then get glycated and are even harder to degrade.

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Study Notes

Cell Aging

  • Cell aging is a progressive decrease in cellular function and viability.
  • Two mechanisms are involved:
    • Genetic factors influencing the aging process.
    • Environmental factors causing the accumulation of metabolic and genetic damage.
    • Balance between metabolic damage and repair mechanisms.
    • Both factors lead to replicative senescence (cells have limited replication capacity).

Genetic Factors

  • DNA repair defects lead to mutation accumulation, reducing cell function and survival, eventually contributing to replicative senescence.
  • Various genetic abnormalities, like IGF-1 pathway dysregulation, disrupt cellular homeostasis and growth regulation, promoting aging-related dysfunction.

Environmental Factors

  • Environmental insults (radiation, toxins, oxidative stress) produce free radicals.
  • Free radicals cause oxidative damage to DNA, proteins, and lipids.
  • This results in a buildup of damaged cellular proteins and organelles.
  • Reduced proteasomal activity (a decline in protein degradation) leads to a buildup of damaged proteins and organelles, further impairing cellular function.

DNA Damage

  • During cellular lifetime, genomic DNA is continually exposed to various hazards, undermining its integrity and functionality.
  • DNA damage can be caused by:
    • Exogenous sources (radiation, chemicals)
    • Endogenous sources (ROS, replication errors, hydrolysis)
  • Accumulation of DNA damage can lead to cell death or senescence.
  • If DNA lesions are not repaired, they become permanent mutations, increasing cancer risk.
  • DNA damage may induce replication arrest and cell death, contributing to aging.
  • In aging, the DNA damage rate increases due to imbalances between the generation and disposal of by-products of cellular metabolism, and a decline in DNA repair efficiency.

Glycation

  • Glycation (Maillard reaction) is another cause of aging.
  • Glycation is the non-enzymatic glycosylation of proteins, lipids, or nucleic acids by glucose or other monosaccharides without enzyme catalysis.
  • Advanced glycation end products (AGEs) are glycated proteins or lipids, which accumulate as a result of sugar exposure.
  • AGEs accumulate in long-lived structural proteins like collagen and elastin, leading to increased stiffness of blood vessels and impaired lung, kidney, heart, and retina functions.
  • AGEs are resistant to proteasome degradation, establishing a feedback loop of reduced proteasomal activity and increased damaged proteins.

Replicative Senescence

  • Replicative senescence is a natural process where cells stop dividing after a finite number of divisions.
  • This is primarily due to progressive shortening of telomeres (protective caps at chromosome ends).
  • This shortening occurs during DNA replication, acting as a natural limit to cell proliferation (Hayflick limit).

Cell Death Mechanisms

  • Apoptosis (programmed cell death):

    • Cells neatly die without damaging neighboring cells.
    • Internal intracellular mechanisms trigger the process.
    • Sculpts embryonic structures during development.
    • Regulates cell numbers.
    • The cell shrinks and condenses.
    • Cytoskeleton collapses.
    • Nuclear envelope disassembles.
    • DNA breaks up.
    • Cell surface changes for phagocytosis.

  • Autophagy:

    • Cell "eats" its own contents, including damaged proteins and organelles.
    • Used for gradual turnover in normal cells and as a death pathway.
    • Doesn't rely on caspases.
    • Activated by factors like growth factors, nutrient deprivation, stress, and protein aggregation.

  • Necrosis:

    • Uncontrolled cell death due to injury (e.g., hypoxia, chemical, physical damage).
    • Cells swell and burst, releasing contents into surrounding tissues.
    • Triggers a non-specific immune response and inflammation.
    • Nuclear changes: pyknosis, karyorrhexis, and karyolysis.
    • Necrosis is different from apoptosis and autophagy as it differs in process from those other cell death pathways.

Autophagy

  • Autophagy is activated by diverse factors; including growth factors, nutrient deprivation, cellular stress and protein aggregation.
  • It is different from apoptosis since it does not involve activation of caspases.
  • Autophagy can be regarded as an alternative to apoptosis, as a cell death pathway.
  • Autophagy employs distinct mechanisms, such as macroautophagy, microautophagy, and chaperone-mediated autophagy.

Programmed Necrosis (Necroptosis)

  • Some forms of necrosis are programmed responses to stimuli like infection or DNA damage.
  • Necroptosis can occur if apoptosis fails.

Summary

  • Cellular aging results from a combination of genetic and environmental factors.
  • Genetic factors influence the aging process, while environments cause metabolic and genetic damage.
  • These factors initiate replicative senescence.
  • Cellular damage can lead to apoptosis, autophagy, or necrosis, each exhibiting different mechanisms.
  • Necroptosis is a programmed form of necrosis.

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Cell Aging & Cell Death Lecture Notes PDF

Description

This quiz explores the mechanisms involved in cell aging, focusing on both genetic and environmental factors. It covers how DNA repair defects and environmental insults contribute to replicative senescence and cellular dysfunction. Test your understanding of the balance between metabolic damage and repair processes.

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