engleski

Sudden Senescence Syndrome and Telomere Shortening

Telomeres are distinctive structures, composed of a repetitive DNA sequences and associated proteins that cap the ends of linear chromosomes. Telomeres are essential for maintaining the integrity and stability of eukaryotic genomes. They shorten by every cell cycle until they reach critical length recognized by checkpoints after which cell enter replicative senescence. Individual senescent cells appear in the culture in sudden and stochastic fashion due to phenomenon referred to as sudden senescence syndrome (SSS). Fraction of senescent cells gradually increases until eventually entire culture cease further divisions. To determine whether individual senescent cells have accelerated telomere shortening, as suggested in a recent literature, we stained young cell culture (population doublings ~25) with DiI which incorporates in membranes of living cells. After each cell division dye distributes among two daughter cells and dilutes to 50% its original abundance. We used flow cytometry in order to separate actively dividing cells (young) from those that cease further divisions (sudden senescence) and analyzed their telomere length by Southern blot analysis. It appeared that these two subpopulations of cells have same telomere lengths. Thus, our result does not support previously proposed accelerated telomere shortening, but indicates that abrupt shortening of one (or few) telomere(s) could cause the onset of sudden senescence observed in a young cell cultures.

SSS; ATS; GTS; cell aging

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