Ageing

MCQ

 





Part A: Telomeres and Cell Division

  1. Telomeres are repetitive nucleotide sequences (TTAGGG in humans) located at the ends of chromosomes. They protect the ends of chromosomes from deterioration or fusion with neighboring chromosomes. Every time a cell divides, telomeres get progressively shorter because DNA polymerase cannot fully replicate the ends of chromosomes.

  2. Telomere attrition occurs with repeated cell divisions, especially in somatic cells (non-reproductive cells). As individuals age or cells divide more frequently, telomeres shorten. Eventually, this shortening reaches a critical length where the cell can no longer divide properly, triggering cellular senescence (a state where cells no longer divide) or apoptosis (cell death).

  3. Telomerase is an enzyme that can replenish telomeres, thus allowing cells to divide without losing important telomeric DNA. Stem cells and germ cells typically express telomerase, enabling them to maintain their telomere length and divide many more times than typical somatic cells.

    • In somatic cells, telomerase is generally inactive, leading to progressive telomere shortening as these cells divide over time.
    • Cancer cells often reactivate telomerase, allowing them to continue dividing indefinitely, leading to uncontrolled growth (a hallmark of cancer).

Part B: Telomere Attrition and Cellular Fate

This part of the diagram illustrates the consequences of telomere shortening:

  1. Telomere length in different cell types:

    • Stem cells maintain telomere length better than somatic cells because they can express telomerase, allowing them to self-renew and divide multiple times without critical telomere shortening.
    • Somatic cells experience telomere shortening with each division, leading to cellular senescence or programmed cell death when the telomeres become critically short.
    • Cancer cells reactivate telomerase, maintaining their telomere length, which enables them to evade normal growth limits and divide uncontrollably.

  2. Consequences of Telomere Attrition:

    • Senescence of mature cells: When somatic cells reach critically short telomere lengths, they stop dividing and enter senescence. This contributes to tissue aging as senescent cells accumulate and no longer function properly.
    • Depletion of stem/progenitor cells: In tissues, stem cells lose their ability to self-renew when their telomeres shorten, leading to a loss of regenerative capacity in tissues. This contributes to tissue dysfunction and aging as fewer new cells can replace old or damaged cells.
    • Tissue dysfunction and aging: The accumulation of senescent cells and depletion of stem/progenitor cells lead to reduced tissue function, which manifests as the physiological signs of aging.

Senescent cells are cells that have permanently stopped dividing but are not dead. While they no longer participate in cell proliferation, they remain metabolically active. Senescence is a protective mechanism to prevent damaged or aged cells from proliferating uncontrollably, which could lead to cancer. However, the accumulation of senescent cells over time is associated with aging and age-related diseases.

Key Features of Senescent Cells:

  1. Permanent Cell Cycle Arrest:

    • Senescent cells are in a state of irreversible growth arrest, meaning they can no longer divide or replicate. This is usually due to extensive DNA damage, critically short telomeres, or other cellular stressors.
    • Senescence is primarily regulated by tumor suppressor pathways, particularly p53, p16, and Rb (retinoblastoma protein), which block the cell cycle.