Table 4 Aged HSC rejuvenation strategies
From: Mechanisms and rejuvenation strategies for aged hematopoietic stem cells
Rejuvenation approach | Mechanism | Functions | Author and year |
|---|---|---|---|
Prolonged fasting | |||
 Prolonged fasting | Reduces circulating IGF-1 levels | Promote stress resistance, self-renewal, and lineage-balanced regeneration | Cheng et al. 2014 [126] |
Gene expression regulation | |||
Satb1 overexpression | Epigenetic modification | Restore the lymphopoietic potential of aged HSCs | Satoh et al. 2013 [127] |
Sirt3 overexpression | ROS levels | Restore the long-term competitive repopulation ability | Brown et al. 2013 [128] |
Sirt7 overexpression | Mitochondrial functions | Rescue myeloid-biased differentiation | Mohrin et al. 2015 [70] |
Pharmacological intervention | |||
 Rapamycin | Inhibition of mTOR | Enhance the regenerative capacity of HSCs from aged mice | Chen et al. 2009 [8] |
 CASIN | Inhibition of Cdc42 | Increase the percentage of polarized cells, restore the spatial distribution of H4K16ac, increase lymphoid output, and reduce myeloid lineage output | Florian et al. 2012 [59] |
 TN13 | Inhibition of p38 MAPK | Decrease ROS level and increase homing ability | Jung et al. 2016 [66] |
 SB203580 | Inhibition of p38 MAPK | Restore the repopulating capacity and maintain quiescence of HSCs | Ito et al. 2006 [9] |
 ABT263 | Inhibition of BCL-2 and BCL-xL | Selectively kill senescent cells | Chang et al. 2016 [129] |
Changing BM niche | |||
 Engraft into a young niche | Changing the BM niche | Restore the age-related transcriptional profiles of HSCs | Kuribayashi et al. 2019 [130] |
 Sympathomimetic supplementation | Influencing BM innervation | Improve multilineage cell production and HSC engraftment | Maryanovich et al. 2018 [109] |