Pure Information (Senescence)

Senescence (Aging)

Hayflick’s Limit:

In 1961 Leonard Hayflick and Paul Moorhead discovered that human cells derived from embryonic tissues can only divide a finite number of times in culture. They divided the cells into 3 phases.

Phase 1: Primary culture, cells grow until they cover the flask.

Phase 2: Cells from Phase 1 have no space for expansion hence are subcultivated i.e. cell suspension divided into two new flasks

Phase 3: Slow dividing cells mark this phase. Cells may or may not die

Cumulative population doublings (CPDs) is the term reserved for expansion of cells and cultures stopped dividing after an average of fifty CPD’s. This phenomenon is known as Hayflick's limit, Phase III phenomenon, or, replicative senescence (RS). There has been a direct relation between the number of CPDs and the species from which the cells were derived.

Some divide 110 times (cells from the Galapagos tortoise) while some only 15 (mouse). Immortal cell lines like embryonic stem cells, stem cells from tumors evade RS.

Biomarkers of RS:

Cell Growth: - The most obvious marker is cell growth. Cells do not continue to divide even vigorously dividing cells reach quiescence during G1 to S phase of the cell growth cycle. External stimulants like growth factors are incapable of stimulating the expansion of senescent cells although senescent cells remain metabolically active.

Cell Morphology: - Senescent cells are bigger and have more diverse morphologies, so also cell density in the confluent culture is less as they are more sensitive to cell-cell inhibition.

Other factors: Enzymes like β-galactosidase has been associated with senescence. Each subcultivation also introduces polyploidy in cells and also mitochondrial DNA undergoes mutations leading to senescence. Cardiac senescence is associated with enhanced expression of Angiotensin Type II receptor subtypes. Senescent cells have also less ability to express heat shock proteins, (the upregulation of heat shock proteins is carried out by heat shock factors). There is upregulation of several genes in vitro cellular senescence. There is also increase in metalloproteinases, which degrade the extracellular matrix.

Stress Induced Senesce:

In normal conditions in human cells O₂ has been exhibited to accelerate growth arrest. Cytotoxic conditions (more than 50% O₂) have been associated with premature cellular senescence. the term stress-induced premature senescence (SIPS) was coined in 1999, at the EMBO workshop of Molecular and Cellular Gerontology, Olivone, Switzerland (Brack et al., 2000).

Reference (http://www.senescence.info/cells.html)