Cellular Senescencecauses And Characteristics

Cellular senescence arrests the growth of mitotically competent cells in response to a variety of stimuli, ranging from chromosomal damage to supraphysiological mitogenic signals. Mitotically competent cells are cells that retain the ability to divide. Examples of such cells include the basal keratinocytes of the skin, the epithelial cells that comprise much of the gastrointestinal tract, liver, and other epithelial organs, the endothelial and smooth muscle cells of the vasculature, the lymphocytes of the hematopoietic system, and the fibroblasts that produce and maintain the stroma that supports many organ structures. Postmitotic cells, by contrast, have lost their ability to proliferate as a consequence of differentiation. Examples of postmitotic cells are mature neurons and differentiated skeletal and heart muscle cells. The senescence response is limited to mitotically competent cells, causing them to lose their capacity for proliferation—essentially irreversibly—such that they now resemble postmitotic cells.

Mitotically competent cells can, and often do, exist in a reversible, growth-arrested state termed quiescence. Quiescent cells can be stimulated to proliferate by appropriate physiological signals. For example, hepatocytes (epithelial cells in the liver) are generally quiescent in vivo, but are readily stimulated to proliferate when the liver is injured or damaged (Chapter 19). The important feature that distinguishes quiescent from senescent (and postmitotic) cells is the reversibility of the growth-arrested state. There are no known physiological signals that can induce senescent or postmitotic cells to resume proliferation.

With regard to pathology, a fundamental difference between mitotically competent and postmitotic cells is their potential to give rise to cancer. Cell proliferation is essential for malignant transformation (1). Because cellular senescence irreversibly arrests cell proliferation, the senescence response is a potent tumor-suppressive mechanism.

How to Stay Young

How to Stay Young

For centuries, ever since the legendary Ponce de Leon went searching for the elusive Fountain of Youth, people have been looking for ways to slow down the aging process. Medical science has made great strides in keeping people alive longer by preventing and curing disease, and helping people to live healthier lives. Average life expectancy keeps increasing, and most of us can look forward to the chance to live much longer lives than our ancestors.

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