MOLECULAR MECHANISMS OF STEM CELL AGING

Katerina Jazbec, Mojca Jež, Mojca Justin, Primož Rožman

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 MATIÄŒNIH CELIC

Povzetek: Staranje veÄceliÄnih organizmov je kompleksen proces, ki je posledica razliÄnih, med seboj dopolnjujoÄih se vzrokov. Eden od teh je tudi staranje matiÄnih celic, katerih bioloÅ¡ka funkcija je nadomeÅ¡Äanje celic, ki propadejo zaradi bolezni, poÅ¡kodb ali normalnega obnavljanja pri ohranjanju homeostaze tkiv. Molekularni mehanizmi, ki so vpleteni v staranje matiÄnih celic, so podobni kot pri staranju telesnih celic. VkljuÄujejo poÅ¡kodbe DNK in mutacije, celiÄno senescenco, izÄrpavanje zalog matiÄnih celic, krajÅ¡anje telomer, epigenetske spremembe (spremembe histonov in DNKA ter poslediÄno spremenjeno izražanje genov), spremembe v mikroRNK, spremembe v zaznavanju hranil in presnovi, zmanjÅ¡ano Å¡tevilo mitohondrijev in njihovo oslabljeno funkcijo, spremembe v mikrookolju in kopiÄenje razliÄnih parakrinih dejavnikov ter izgubo celiÄne polarnosti in proteostaze. MatiÄne celice so razvile posebne mehanizme, s katerimi kompenzirajo s staranjem povezano kopiÄenje napak in ohranjajo svojo matiÄnost, vendar jih ti mehanizmi v dobri kondiciji lahko ohranjajo le doloÄen Äas. V Älanku opisujemo razliÄne mehanizme staranja matiÄnih celic in njihove posledice.

KljuÄne besede: matiÄne celice; staranje; hranilna snov; zaznavanje; niÅ¡a


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DOI: https://doi.org/10.26873/SVR-545-2018

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