MOLECULAR MECHANISMS OF STEM CELL AGING

Abstract

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 MATIČNIH CELIC Povzetek: Staranje večceličnih organizmov je kompleksen proces, ki je posledica različnih, med seboj dopolnjujočih se vzrokov. Eden od teh je tudi staranje matičnih celic, katerih biološka funkcija je nadomeščanje celic, ki propadejo zaradi bolezni, poškodb ali normalnega obnavljanja pri ohranjanju homeostaze tkiv. Molekularni mehanizmi, ki so vpleteni v staranje matičnih celic, so podobni kot pri staranju telesnih celic. Vključujejo poškodbe DNK in mutacije, celično senescenco, izčrpavanje zalog matičnih celic, krajšanje telomer, epigenetske spremembe (spremembe histonov in DNKA ter posledično spremenjeno izražanje genov), spremembe v mikroRNK, spremembe v zaznavanju hranil in presnovi, zmanjšano število mitohondrijev in njihovo oslabljeno funkcijo, spremembe v mikrookolju in kopičenje različnih parakrinih dejavnikov ter izgubo celične polarnosti in proteostaze. Matične celice so razvile posebne mehanizme, s katerimi kompenzirajo s staranjem povezano kopičenje napak in ohranjajo svojo matičnost, vendar jih ti mehanizmi v dobri kondiciji lahko ohranjajo le določen čas. V članku opisujemo različne mehanizme staranja matičnih celic in njihove posledice. Ključne besede: matične celice; staranje; hranilna snov; zaznavanje; niša