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These cells then become slightly more specialized, and are referred to as multipotent cells.

Aging - Senescence in mammals |

A multipotent stem cell has the potential to differentiate into different types of cells within a given cell lineage or small number of lineages, such as a red blood cell or white blood cell. Finally, multipotent cells can become further specialized oligopotent cells. An oligopotent stem cell is limited to becoming one of a few different cell types. In contrast, a unipotent cell is fully specialized and can only reproduce to generate more of its own specific cell type. Stem cells are unique in that they can also continually divide and regenerate new stem cells instead of further specializing.

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They include the embryonic stem cells of the embryo, fetal stem cells of the fetus, and adult stem cells in the adult. One type of adult stem cell is the epithelial stem cell, which gives rise to the keratinocytes in the multiple layers of epithelial cells in the epidermis of skin.


Adult bone marrow has three distinct types of stem cells: hematopoietic stem cells, which give rise to red blood cells, white blood cells, and platelets Figure 1 ; endothelial stem cells, which give rise to the endothelial cell types that line blood and lymph vessels; and mesenchymal stem cells, which give rise to the different types of muscle cells.

When a cell differentiates becomes more specialized , it may undertake major changes in its size, shape, metabolic activity, and overall function. Because all cells in the body, beginning with the fertilized egg, contain the same DNA, how do the different cell types come to be so different? The answer is analogous to a movie script. The different actors in a movie all read from the same script, however, they are each only reading their own part of the script. In biology, this is referred to as the unique genetic expression of each cell. In order for a cell to differentiate into its specialized form and function, it need only manipulate those genes and thus those proteins that will be expressed, and not those that will remain silent.

A transcription factor is one of a class of proteins that bind to specific genes on the DNA molecule and either promote or inhibit their transcription Figure 2. Stem Cell Research Stem cell research aims to find ways to use stem cells to regenerate and repair cellular damage. Over time, most adult cells undergo the wear and tear of aging and lose their ability to divide and repair themselves.

Stem cells do not display a particular morphology or function.

Senescence in mammals

Adult stem cells, which exist as a small subset of cells in most tissues, keep dividing and can differentiate into a number of specialized cells generally formed by that tissue. These cells enable the body to renew and repair body tissues. The mechanisms that induce a non-differentiated cell to become a specialized cell are poorly understood.

In a laboratory setting, it is possible to induce stem cells to differentiate into specialized cells by changing the physical and chemical conditions of growth. Several sources of stem cells are used experimentally and are classified according to their origin and potential for differentiation.

Human embryonic stem cells hESCs are extracted from embryos and are pluripotent.

The adult stem cells that are present in many organs and differentiated tissues, such as bone marrow and skin, are multipotent, being limited in differentiation to the types of cells found in those tissues. The stem cells isolated from umbilical cord blood are also multipotent, as are cells from deciduous teeth baby teeth.

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Researchers have recently developed induced pluripotent stem cells iPSCs from mouse and human adult stem cells. These cells are genetically reprogrammed multipotent adult cells that function like embryonic stem cells; they are capable of generating cells characteristic of all three germ layers.

Because of their capacity to divide and differentiate into specialized cells, stem cells offer a potential treatment for diseases such as diabetes and heart disease Figure 3. Cell-based therapy refers to treatment in which stem cells induced to differentiate in a growth dish are injected into a patient to repair damaged or destroyed cells or tissues. Many obstacles must be overcome for the application of cell-based therapy. Also, the destruction of embryos to isolate embryonic stem cells raises considerable ethical and legal questions.

In contrast, adult stem cells isolated from a patient are not seen as foreign by the body, but they have a limited range of differentiation. If the telomeres shrink too much or are damaged, cells undergo apoptosis or enter senescence. Telomere damage has clear effects on aging. Mice with short telomeres have diminished life spans and reduced stem-cell and organ function, while mice whose telomerase is enhanced in adulthood age more slowly EMBO Mol Med , , In humans, mutated telomerase is associated with disorders involving organ dysfunction and elevated cancer risk J Clin Invest , , In recent years, researchers have also shown that telomeres are targets of stress-induced DNA damage Nat Comm , , Once telomeres have been damaged, they are difficult to repair.

They protect chromosomes from fusing with one another by recruiting protein complexes called shelterins that prevent overzealous DNA repair proteins from mistaking loose ends for double-strand breaks. This may also prevent repair proteins from accessing legitimate DNA damage, however, leading to cell death or senescence. Telomeres may be especially prone to DNA damage in order to protect the body from cancer, Passos suggests.

Because they are disproportionately damaged by stressors, and because telomere damage so often leads to senescence, they could be like canaries in coal mines, warning cells that carcinogens are present. Telomeres may, in fact, be DNA-damage sensors that shut down cell proliferation in times of stress, Passos says. This is a double-edged sword, as senescence lowers cancer risk but also leads to symptoms of aging.

Life depends on proper protein function. And proper protein function is all about proper protein folding. Misshapen proteins are often rendered useless and can clump together with other misfolded proteins inside cells. It is not yet clear whether protein misfolding leads to aging, but it appears that it is an almost inevitable physiological reality that the two coincide. To add insult to injury, advancing age also brings about the decline of molecular chaperones that aid in the folding process and of protective pathways that normally help clear misfolded proteins from cells.

The model organism C. Soto says that problems with protein folding might be central to the multitude of molecular deficiencies that characterize an aging body. After all, normal protein folding is necessary for gene expression, enzyme function, and a host of other crucial physiological events. And if protein misfolding does act as a sort of linchpin in aging, correcting it may be a way of staving off a host of age-related maladies or even aging itself, Soto adds.

Beginning in the s, scientists studying model organisms observed phenomena that contradicted the free radical theory. Such evidence is helping to shape a new view of oxidative damage to mitochondria.

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There is a limit to how much damage the organelle can handle, however, and mitochondrial dysfunction may well contribute to aging. Recent evidence in mice shows that mutations in mitochondrial DNA are linked with shortened life span Sci Rep , , Healthy adults produce about billion new red blood cells each day to replace the same number removed from circulation every 24 hours. But the rate of blood-cell production declines with age.

Stem Cells

For this and other reasons, around 10 percent of people age 65 and older are anemic. Scientists are now homing in on how hematopoietic stem cells HSCs and other stem-cell populations show reduced regenerative capacity with age. This reduced capacity for DNA damage repair can let harmful mutations linger. Researchers have also linked epigenetic alterations, such as locus-specific changes in DNA methylation, to the reduced regenerative capacity of stem cells with age.

And age-related shifts in the environment in which stem cells divide and differentiate, dubbed the stem-cell niche, may also contribute to stem-cell aging. For example, as Hartmut Geiger of the University of Ulm, Germany, and his colleagues showed in , age-related changes in supportive niche cells influence hematopoietic progenitor cell populations: young microenvironments fostered more homogeneous groups of cells as compared with aged ones PLOS ONE , doi Exactly why and how stem cells slow down with age is still a mystery.

Stem cells and other cells that undergo damage and decline do not age in isolation. Researchers are finding that some processes of aging influence the release of regulators that circulate in the blood. They do negative things, and they persist.