Cellular Senescence

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Cellular senescence is the point at which our cells stop dividing and growing due to damage or lack of necessary components. As cells age, they lose their ability to actively divide and start to undergo senescence.

Senescence refers to a pause in the cell cycle, usually in response to damage. Young senescent cells are presumably cleared by the immune system, but in older tissues, they stick around, secreting harmful proinflammatory signals like IL-6 and IL-8 that damage our bodies further.

As one would guess, the DNA damage and oxidative stress responses, via p53 and AMPK, induce senescence via the retinoblastoma pathway. And telomere shortening causes cells to stop replicating, reinforcing the senescent phenotype.

The cell cycle regulator, p16, plays a still-mysterious role in aging-related senescence. Levels of p16 are more correlated to chronological age than are the levels of any other protein, but its precise regulation in the context of aging is not clear. Developmental signaling, such as by the Id proteins and microRNAs, is involved.

The emerging theme is that it’s not enough to measure one or two biomarkers to unequivocally define the senescent state. To fully characterize aging cells, measure at least a few of the following phenotypic markers: secretory phenotype, beta galactosidase expression, proliferation, heterochromatic foci, flatness of morphology and chromatin alterations.


Senescence Pathways and Regulators
(Click image to enlarge.)

Many pathways lead to senescence, and the latest research points to microsRNAs playing a key role. Adapted from Gorospe M, Abdelmehsen K. Micro Regulators come of age in senescence Trends Genet 2011; 27(6).233-41.
Did you know?
Senescence is defined as the state of being old, or the process of becoming old. In plants, it is the phase from fullmaturity to death, as seen with leaves.

It refers not only to being or becoming old, but also the deterioration with age.

In terms of cellular senescence, it is the stage at which cells, lose their ability to grow and divide, which can occur due to damage or as a result of loss in molecular components.


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