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E. Mejia-Ramirez and M.C. Florian et al.
Perspectives for rejuvenation and therapeutic strategies
In this review, we have summarized some of the most recent and relevant information about the intrinsic fac- tors that affect HSC upon aging. In general, we can iden- tify at least five biological processes, which we would define as intrinsic HSC aging mechanisms (Table 1 and Figure 4). DNA damage, metabolism, epigenetics/chro- matin architecture, proteostasis, and signaling. However, the cell cannot compartmentalize hermetically each one of these processes. This is the reason why the intercon- nections between these biological processes will be a key aspect in deciphering the extent of the impact of aging on HSC. For instance, the levels of several metabolites like SAM or ketoglutharate affect the activity of methy- lases, which in turn have an effect on the epigenetics of the cell.35 Investigating and understanding cellular and molecular mechanisms of HSC aging will increase the
possibility of defining new pharmacological targets to reduce the negative effects of aging and promote “healthy aging”.
We are aware that most aging mechanisms that we have reviewed here have been studied in the murine or in non- human systems. Nevertheless, we would like to empha- size the progress achieved so far and the importance of pursuing an integrative research approach, to connect all the aspects affecting stem cell aging. A broader view of this process might indeed be central in bridging the gap to translation in the human system.
Acknowledgment
This work was supported by the Deutsche Forschungsgemeinschaft (DFG or German Research Foundation) FOR2674 and SFB1074 to MCF and by Ministerio de Ciencia, Innovación y Universidades (Spanish Ministry of Science, Innovation and University) PGC2018-102049-B-I00 and RYC2018-025979-I to MCF.
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