Unlocking the Secrets
of Cell Senescence

Researchers have developed the first technique for
identifying those cells within living organisms that have reached old age.

Senescent cells, as they are called, are no longer capable of dividing yet remain metabolically active. Furthermore, they exhibit changes in form and function which may lead to age-related changes such as the difference between the supple skin of a child and the wrinkled skin of the elderly.

Scientists know senescence is an irreversible stage in the life of the cell but are intent upon learning much more about this mysterious process. Senescence may be an underlying cause of aging that evolved to prevent the uncontrolled growth of cells-- what we know as cancer.

The simple, rapid, and inexpensive test for identifying senescent cells developed by LBL life scientists Judy Campisi, Goberdhan Dimri, and colleagues at several other research institutions gives science a powerful new tool for examining senescence.

A new test developed by LBL researchers uses blue stain to detect the presence of senescent cells. The assay top left shows young tissue with no presence of blue; top right is young sunburned tissue, also negative. Older tissue cells, pictured in the bottom four assays, contain blue areas revealing evidence of the existence of senescent cells.

Campisi says that because it had not been possible to detect or study senescent cells in a living animal (in vivo), research until now has focused on cells grown in culture. Campisi notes that the new technique has provided the first actual evidence that senescent cells exist in living organisms, and that they accumulate with age.

The ability to distinguish senescent cells in vivo allows researchers to take a much closer look at their suspected role in tumor suppression. "One could say that senescence is the opposite of cancer," says Campisi. "Some of the same genes that drive uncontrolled proliferation in cancer seem to be under tight control, or actually turned off, in senescence."

Scientists now can screen compounds for senescence-inducing or senescence-delaying activity. These compounds may have anti-tumor or anti-aging properties. The technique also can be used to identify genes able to stop cancerous cells from replicating endlessly. Likewise, it should help in the isolation of genes that trigger premature aging syndromes.

Campisi said the technique emerged after researchers discovered that a variety of senesecent human cells including two major types of skin cells, fibroblasts and keratinocytes, produce or express a particular form of an enzyme, beta-galactosidase. The senescent form of beta-galactosidase either is absent or virtually absent in presenescent cells. Based on this finding, a simple assay was developed that uses a stain to detect the presence of the enzyme. Old cells -- those that express beta-galactosidase--turn blue.

Campisi said it would be foolish to attempt to completely reverse senescence in cells because the cessation of growth also prevents cancer. On the other hand, the ability to manage or alter the changes in function that are a part of senescence has obvious value.

The biotech industry one day may attempt to change the phenotypes of senescent cells, for instance as a route to deal with the skin problems experienced by older people. Again, the new assay should prove helpful, serving as a first line test to both discover and monitor the efficacy of therapeutic drugs or genes.

-- Jeffery Kahn

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