Reduction, proliferation, and differentiation defects of stem cells over time: a consequence of selective accumulation of old centrioles in the stem cells?

BACKGROUND: All molecules, structures, cells in organisms are subjected to destruction during the process of vital activities. In the organisms of most multicellular animals and humans, the regeneration process always takes place: destruction of old cells and their replacement with the new. The replacement of cells happens even if the cells are in perfect condition. The sooner the organism destroys the cells that emerged a certain time ago and replaces them with the new (i.e., the higher is the regeneration tempo), the younger the organism is. DISCUSSION: Stem cells are progenitor cells of the substituting young cells. Asymmetric division of a mother stem cell gives rise to one, analogous to the mother, daughter cell, and to a second daughter cell that takes the path of further differentiation. Despite such asymmetric divisions, the pool of stem cells diminishes in its quantity over time. Moreover, intervals between stem cell divisions increase. The combination of these two processes causes the decline of regeneration tempo and aging of the organism. CONCLUSION: During asymmetric stem cell divisions daughter cells, with preserved potency of the stem cell, selectively conserve mother (old) centrioles. In contrast with molecules of nuclear DNA, reparations do not take place in centrioles. Hypothetically, old centrioles are more subjected to destruction than other structures of a cell-which makes centrioles potentially the main structure of aging.

RNA in centrosomes: structure and possible functions.

A novel RNA was detected in the centrosomes of Spisula solidissima mollusk oocytes in 2006. This RNA was named centrosomal RNA (cnRNA); five different cnRNAs were described. During the sequencing of the first transcript, cnRNA 11, it was discovered that the transcript contained a conserved structure--a reverse transcriptase domain. In a 2005 study, we speculated about several possible mechanisms for determining the most important functions of centrosomal structures and referred to one of them as an "RNA-dependent mechanism". The discovery of RNA specific to the centrosome is indirect evidence of the centrosomal hypothesis of cellular aging and differentiation. The presence of a reverse transcriptase domain in this type of RNA, together with its uniqueness and specificity, makes the centrosome a place of information storage and reproduction.

Discovery of centrosomal RNA and centrosomal hypothesis of cellular ageing and differentiation.

In 2006, a group of scientists studying centrosomes of Spisula solidissima mollusc oocytes under the leadership of Alliegro (Alliegro, M.C.; Alliegro, M.A.; Palazzo, R.E. Centrosome-associated RNA in surf clam oocytes. Proc. Natl. Acad. Sci. USA 2006, 103(24), 9034-9038) reliably demonstrated the existence of specific RNA in centrosome, called centrosomal RNA (cnRNA). In their first article, five different RNAs (cnRNAs 11, 102, 113, 170, and 184) were described. During the process of full sequencing of the first transcript (cnRNA 11), it was discovered that the transcript contained a conserved structure-a reverse transcriptase domain located together with the most important centrosomal protein, γ-tubulin. In an article published in 2005, we made assumptions about several possible mechanisms for determining the most important functions of centrosomal structures and referred to one of them as a "RNA-dependent mechanism." This idea about participation of hypothetic centrosomal small interference RNA and/or microRNA in the process was made one year prior to the discovery of cnRNA by Alliegro's group. The discovery of specific RNA in a centrosome is indirect evidence of a centrosomal hypothesis of cellular ageing and differentiation. The presence of a reverse transcriptase domain in this type of RNA, together with its uniqueness and specificity, makes the centrosome a place of information storage and reproduction.

Gerontology research in Georgia.

Gerontology research carried out in different scientific centers of Georgia follows the basic directions of most work in this field: epidemiology, investigation of the mechanisms of aging, and finding ways to prevent senile pathologies and to prolong life. The genealogy and epidemiology of long-living peaple have been studied in areas with high occurrence of these people by considering the sex ratio and social status of the long-living, the influence of environmental factors, and the development of senile pathologies. According to the centrosome (centriole) model of aging, the centrosomes and the cytoskeleton, important structures in cellular differentiation and morphogenesis, may be involved in the initiation of the replication senescence mechanism. Our analysis of genetic studies shows that progressive chromosome heterochromatinization (condensation of eu- and heterochromatin regions) occurs in aging. Decreases in the repair processes and increases in the frequency of chromosome aberrations during aging are secondary to this progressive chromosome heterochromatinization. Chromosome heterochromatinization is a key factor in aging but may be reversible under the influence of bioregulators, some chemical substances, and heavy metal salts. The study of chromosome heterochromatinization may provide clues to the potential for prolonging the human lifespan.