Cellular senescence

Definition

Cellular senescence is a state in which cells cease to divide and grow, often as a response to stress or damage, while remaining metabolically active. This process serves as a protective mechanism against cancer, limiting the proliferation of damaged cells, but it can also contribute to aging and age-related diseases due to the accumulation of senescent cells in tissues over time.

5 Must Know Facts For Your Next Test

1. Cellular senescence can be triggered by various factors including DNA damage, oxidative stress, and telomere shortening.
2. While senescence plays a protective role in preventing cancer by stopping the division of potentially malignant cells, an accumulation of senescent cells can lead to chronic inflammation and tissue dysfunction.
3. Senescent cells are known to be metabolically active, often secreting factors that influence neighboring cells and can impact overall tissue health.
4. Research indicates that removing senescent cells from tissues can improve healthspan and delay age-related diseases in animal models.
5. In the context of aging, cellular senescence is believed to contribute to the decline in tissue function and regeneration capacity, linking it directly to the aging process.

Review Questions

• How does cellular senescence serve as a protective mechanism against cancer development?
  • Cellular senescence helps prevent cancer by halting the division of damaged or potentially oncogenic cells. When a cell undergoes stress or damage, it can enter a state of senescence instead of continuing to proliferate. This stops the propagation of mutations that could lead to tumor formation. However, while this is beneficial in the short term, the accumulation of senescent cells over time can have negative effects on tissue health.
• Discuss the role of telomeres in the process of cellular senescence and their connection to aging.
  • Telomeres play a crucial role in cellular senescence as they shorten with each cell division. Once telomeres reach a critical length, they trigger a DNA damage response that leads to senescence. This connection between telomere shortening and senescence is significant for understanding aging, as many cells become senescent over time due to this process. The eventual accumulation of senescent cells contributes to age-related decline in tissue function.
• Evaluate the implications of the Senescence-Associated Secretory Phenotype (SASP) on tissue health and potential therapeutic interventions targeting cellular senescence.
  • The SASP can have both beneficial and detrimental effects on tissue health. On one hand, it can promote tissue repair and regeneration; on the other hand, the chronic inflammation and signaling caused by SASP factors can lead to tissue dysfunction and age-related diseases. This dual nature has led researchers to consider therapeutic interventions that selectively target or clear senescent cells from tissues. Such approaches may enhance tissue health, improve regenerative capacities, and potentially extend healthspan by mitigating the negative impacts associated with cellular senescence.

Related terms

Apoptosis: A programmed cell death mechanism that eliminates damaged or unwanted cells in a controlled manner, contrasting with senescence where cells remain alive but non-dividing.

Telomeres: Repetitive nucleotide sequences at the ends of chromosomes that protect them from deterioration; telomere shortening is a key factor triggering cellular senescence.

SASP (Senescence-Associated Secretory Phenotype): A phenomenon where senescent cells secrete pro-inflammatory factors, growth factors, and proteases that can affect nearby cells and contribute to tissue dysfunction.