Problem 3 - Biology of Aging

Question

List the order of events in programmed senescence, occurring at the cellular level.

Step-by-Step Solution

Answer

The order of events in programmed senescence includes: initiation of senescence, establishment of senescence, maintenance of senescence, cell death or survival, and finally clearance of senescent cells by the immune system.

Step 1: Initiation of Senescence

The initiation of senescence is usually triggered by a number of factors such as DNA damage, telomere shortening, oxidative stress or oncogene activation.

Step 2: Establishment of Senescence

During this phase, cells undergo a number of changes including enlarging, flatting and increasing their granularity. They also express markers of senescence such as the senescence-associated \(\beta\)-galactosidase activity (SA-\(\beta\) gal), chromatin rearrangement and the secretion of pro-inflammatory cytokines sees a dramatic increase.

Step 3: Maintenance of Senescence

Maintenance of the senescent state is regulated by two tumor suppressors p53 and retinoblastoma (Rb). If these genes are lesioned, the cell can escape from senescence.

Step 4: Cell Death or Survival

If the damage is irreparable, the cell would either die due to autophagy or apoptosis. In some cases, the senescent cell could survive, but become functionally different.

Step 5: Clearance of Senescent Cells

Finally, the immune system identifies and clears senescent cells. If the immune system fails to clear these cells, they can contribute to aging and the development of age-related diseases.