MOLECULAR MECHANISMS OF STEM CELL AGING

The aging of multicellular organisms is a complex process, which is a result of various mutually complementary causes. One of these causes is the aging of stem cells. The biological function of stem cells is the replacement of cells that are lost due to illness, injury or normal fluctuations in the maintenance of tissue homeostasis. Molecular mechanisms involved in stem cell aging are similar to those involved in the aging of somatic cells. They include DNA damage and mutations, cell senescence, stem cell exhaustion, telomere shortening, epigenetic changes (alterations of histones and DNA and the consequent dysregulation of gene expression), changes in microRNAs, changes in metabolism, nutrient sensing, decline in mitochondrial integrity and biogenesis, alterations in microenvironment, accumulation of paracrine factors, and loss of cell polarity and proteostasis. Stem cells have developed special mechanisms that compensate for age-related accumulations of errors and they manage to maintain their stemness for a long time, however, they are able to keep cells in a good condition only for a limited period. This article describes the various mechanisms of stem cell aging and their consequences. Key words: stem cell; aging; nutrient sensing; niche MOLEKULARNI MEHANIZMI STARANJA MATICNIH CELIC Povzetek: Staranje veccelicnih organizmov je kompleksen proces, ki je posledica razlicnih, med seboj dopolnjujocih se vzrokov. Eden od teh je tudi staranje maticnih celic, katerih bioloska funkcija je nadomescanje celic, ki propadejo zaradi bolezni, poskodb ali normalnega obnavljanja pri ohranjanju homeostaze tkiv. Molekularni mehanizmi, ki so vpleteni v staranje maticnih celic, so podobni kot pri staranju telesnih celic. Vkljucujejo poskodbe DNK in mutacije, celicno senescenco, izcrpavanje zalog maticnih celic, krajsanje telomer, epigenetske spremembe (spremembe histonov in DNKA ter posledicno spremenjeno izražanje genov), spremembe v mikroRNK, spremembe v zaznavanju hranil in presnovi, zmanjsano stevilo mitohondrijev in njihovo oslabljeno funkcijo, spremembe v mikrookolju in kopicenje razlicnih parakrinih dejavnikov ter izgubo celicne polarnosti in proteostaze. Maticne celice so razvile posebne mehanizme, s katerimi kompenzirajo s staranjem povezano kopicenje napak in ohranjajo svojo maticnost, vendar jih ti mehanizmi v dobri kondiciji lahko ohranjajo le dolocen cas. V clanku opisujemo razlicne mehanizme staranja maticnih celic in njihove posledice. Kljucne besede: maticne celice; staranje; hranilna snov; zaznavanje; nisa