28 September 2011

Stem cells and aging

Review of research articles published in 2009 that have made or will make a significant contribution to the study of aging – Part 6.

In 2009, several proofs were obtained that excessive activation of signaling mechanisms can lead to depletion of the potential of stem cells and, conversely, "longevity genes" are able to prevent their depletion. Thus, mTOR mediated Wnt-induced depletion of epidermal stem cells and the formation of skin aging phenotypes [44]. Moreover, excessive activation of mTORC1 caused hyperproliferation and subsequent depletion of hematopoietic stem cells. The use of pharmacological approaches has shown that the PTEN, TSC1 and PML genes regulate the maintenance of a population of hematopoietic stem cells using mTORC1 [45]. It was also found that transcription factors of the FOXO family are necessary to maintain homeostasis of adult neural stem cells [46, 47]. It is important to note that the aging of stem cells can be prevented by pharmacological methods [40, 44]. The PI3K-AKT-FoxO signaling mechanism, which is an integral component of the life expectancy regulation system of lower organisms, plays an important role in controlling the proliferation and renewal of neural progenitor stem cells (NSCs). Mice without the FoxO gene demonstrate an increase in brain size and the level of proliferation of nerve progenitor cells in the early stages of postnatal development, after which there is a pronounced premature extinction of the NSC population and, accordingly, neurogenesis in the brain of adult animals [46].

In addition, the researchers were able to restore the functions of aging organs with the help of young supporting stem cells. According to the data published in the first issue of the journal Aging, infusions of bone marrow cells of young adult female mice once a month maintained the fertility of aging females for a long time after they reached the usual age of loss of reproductive ability [48]. The reproductive function-supporting effect was observed regardless of when the introduction of cells was initiated, at a young or middle age, however, it was characteristic only for cells isolated from the bone marrow of female donors. With this "rejuvenation", mature eggs were formed not from the germ cells of the donor bone marrow, but from the recipient's gametocytes, the functioning of which was stimulated by infusions [48, 49]. In confirmation of this, the results of very recent studies have shown that the ovaries of old mice that do not have eggs contain a small population of gametocytes, which, when introduced into the microenvironment of a young healthy ovary, can turn into immature eggs located inside the follicles [49]. Thus, the inability to reproduce in old age may be at least partially due to the depletion of the somatic microenvironment (niche) that supports the functioning of cells.

Continuation: Core reprogramming and physiological aging.

Portal "Eternal youth" http://vechnayamolodost.ru28.09.2011

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