Stem cell dysfunction, aging and cancer
Cancer and aging are linked by stem cell dysfunction
LifeSciencesToday based on the materials of the Centre for Genomic Regulation:
Understanding aging: Stem cell dysfunction links cancer and agingAging is a complex biological process in which a steady decline in the functional capabilities of the body eventually leads to its death.
However, aging is also associated with the development of many diseases, including cancer, which is often called the "disease of aging". Aging not only has a decisive impact on human health, but also, requiring huge financial costs, puts a heavy burden on healthcare. Therefore, in order to increase not only human life expectancy, but also the duration of its healthy period, it is so important to understand the process of normal aging.
Despite the actively conducted research around the world, the causes of aging are still unknown. In particular, it is not entirely clear why functional decline occurs over time. Scientists at the Centre for Genomic Regulation (Centre for Genomic Regulation), Barcelona, have found an important key to understanding the aging process and the development of diseases caused by it, in particular cancer.
The Spanish scientists conducted their experiments on the skin of young and old mice, since the skin is one of the most rapidly aging tissues. Indeed, many of the visible signs of aging of the body are the result of changes in this particular tissue, including its thinning and the appearance of wrinkles, impaired hair growth, as well as a decrease in the ability to heal wounds.
The cover of the magazine Genes & Development. The Jak-Stat signaling pathway mediates stem cell dysfunction in aging skin. Here is an immunofluorescence analysis of the epidermis of an old mouse tail treated with a Jak inhibitor, stained with antibodies against CDP (green), a marker of actively growing hair follicles, as well as DAPI dye (blue) for visualization of nuclei and isolation of hair rods. Treatment of aging skin with a Jak inhibitor causes the growth of hair follicles and proliferation in the aging epidermis. (Photo: genesdev.cshlp.org )
The skin, like the whole body, is constantly being renewed, replacing dead and damaged cells with new and healthy ones. At the same time, all tissues depend on a population of specialized cells known as stem cells.
"These cells are unique because they are able to differentiate into all types of cells of a given tissue. In addition, they are more resistant to stress and damage than differentiated ones. This process of rejuvenation and renewal is something that is believed to occur throughout life," explains the first author of the study published in the journal Genes & Development, postdoctoral fellow Jason Doles.
To find out whether the weakening of stem cell function can contribute to aging, scientists studied skin stem cells during their aging process. The main conclusion they made is that in the process of aging, skin stem cells really lose the ability to properly perform their functions.
"We have found that during the aging process, the most important changes occur in stem cells, and older animals have more pronounced disorders of their growth. In addition, old stem cells are not able to withstand stress as effectively as young ones. This strongly supports the idea that changes in the function of stem cells can indeed cause the aging process," says study leader William Keyes, head of the laboratory of mechanisms of cancer and aging.
Immuno-staining of a transgenic (keratin-15-green fluorescent protein) reporter in the epidermis of the mouse tail highlights a population of stem cells undergoing age-related changes. (Photo: Centre for Genomic Regulation)
Scientists have managed to discover new processes that control the aging of skin stem cells and link the aging process with diseases such as cancer. Indeed, recent work by the same group has shown that it is stem cells that become uncontrolled in the development of squamous cell carcinoma, a deadly type of skin cancer. In this study (Age-associated inflammation inhibits epidermal stem cell function), after sequencing the RNA of old stem cells, cytokine analysis and functional tests, scientists determined the probable cause of their loss of function in the aging process. They showed that during normal aging, the skin changes and produces many different proteins that mediate inflammation, and that it is the abnormal synthesis of these inflammatory mediators that contributes to the extinction of stem cell function. Given that the link between inflammation and cancer development has been known for a long time, the study contributes to its understanding.
Taken together, these data help explain what is most likely the main cause of aging and how this process develops. In addition, having identified inflammation as the cause of stem cell dysfunction, the work reveals the probable causes of cancer development.
Portal "Eternal youth" http://vechnayamolodost.ru18.10.2012