telomerase and senescence

Quiescent cells

• Also known as G0

• State of cellular division in which cells “leave” the cell cycle to remain in a semi-permanent state of no longer actively dividing

• Cells are still metabolically active, just not dividing

• Reversible. Cells can enter and exit from G0 depending on various factors/stimuli

• Primary stimulation – lack of nutrition and growth factors → why they don’t divide

• can go into dividing state or non-dividing state, it’s reversible

Adult stem cells

capable of regenerating tissues when needed, but otherwise inactive

Hepatocytes

metabolically active liver parenchymal cells that do not divide, but can enter the cell cycle to regenerate liver tissue when needed

Fibroblasts

active connective tissue cells that become mitotically active during injury/inflammation to mediate repair/regeneration

Senescent Cells

• State of cellular division in which cells permanently arrest somewhere within the cell cycle. Can occur in G1, S, or G2

• Cells can remain metabolically active, but cannot divide

• Irreversible. Once cells undergo senescence, they are permanently arrested

• Primary stimulation – aging, major DNA damage

• CANNOT go into dividing state or non-dividing state, it only stays in non-dividing

Replicative senescence

 limited replicative potential of normal cells due to telomere attrition or dysfunction

Stress-induced senescence

premature senescence (before telomeres shorten) due to various stressors (e.g., oxidative damage, DNA damage, oncogene activation, etc.)

Postmitotic cellular senescence

permanent growth arrest of terminally differentiated cell types (e.g., neurons, myocytes, adipocytes, etc.)

KNOW ALL MOLECULAR PLAYERS

Telomere

• Non-coding, repetitive sequences (TTAGGG) at the ends of linear chromosomes

• Shorten with each DNA replication due to inability of lagging strand to synthesize (no place to put a primer to start new Ozakai fragment)

• Associated with replicative senescence – when telomeres become sufficiently shortened, stimulates irreversible cell cycle arrest

Shelterin in Telomeres

protein complex bound to telomeric repeats

• it acts as a protection for these ends so they’re not recognized as DNA damage

Telomere loops

ensure that telomere ends are not exposed and are protected from premature degradation

• tuck into themselves to protect the ends and not recognized as DNA damage