A state-of-the-art review on the MicroRNAs roles in hematopoietic stem cell aging and longevity

Abstract

Aging is a biological process determined through time-related cellular and functional impairments, leading to a decreased standard of living for the organism. Recently, there has been an unprecedented advance in the aging investigation, especially the detection that the rate of senescence is at least somewhat regulated via evolutionarily preserved genetic pathways and biological processes. Hematopoietic stem cells (HSCs) maintain blood generation over the whole lifetime of an organism. The senescence process influences many of the natural features of HSC, leading to a decline in their capabilities, independently of their microenvironment. New studies show that HSCs are sensitive to age-dependent stress and gradually lose their self-renewal and regeneration potential with senescence. MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally inhibit translation or stimulate target mRNA cleavage of target transcripts via the sequence-particular connection. MiRNAs control various biological pathways and processes, such as senescence. Several miRNAs are differentially expressed in senescence, producing concern about their use as moderators of the senescence process. MiRNAs play an important role in the control of HSCs and can also modulate processes associated with tissue senescence in specific cell types. In this review, we display the contribution of age-dependent alterations, including DNA damage, epigenetic landscape, metabolism, and extrinsic factors, which affect HSCs function during aging. In addition, we investigate the particular miRNAs regulating HSCs senescence and age-associated diseases. Video Abstract.

Keywords: Aging; Anti-aging; Hematopoietic stem cell; MicroRNA.

Fig. 1

miRNA biogenesis and function in the cell

Fig. 2

Maturated bone marrow (BM) stem cell niche. In the osteoblast niche (by using Notch, Wnt, and PGE-2 pathways), HSCs exist near the osteoblast, which is regulated by bone morphogenetic protein (BMP). In addition, HSCs are as well as exist near the blood vessels in the vascular niche. The stromal cell-derived factor 1 (SDF1), as well as recognized as C-X-C motif chemokine 12 (CXCL12), controlled the immigration of HSCs in the blood flow to the BM. In vivo, the osteoblast and vascular niches may be close to one another. The BM environment also includes stromal cells, which protect hematopoiesis, such as the generation of cytokines, including c-Kit ligand, which was induced by stem cells and progenitors

Fig. 3

The schematic comparison of aged and young HSCs function in BM. While the total number of cells with regenerative potential in the BM of elderly adults increases, the extent to which specific old cells can still chip away at blood cell production becomes highly variable. Young HSCs are home to the BM and centralize near endosteum. They have great self-renewal and regenerative potential and a moderate differentiation ability towards lymphoid and myeloid progenitor cells. The location of elderly HSCs in the BM is distinguished from that of young HSCs; elderly HSCs centralize away from the endosteal stem cell niche following their transplantation

Fig. 4

Essential pathways that aid senescence in HSCs. Although it may be challenging to restore some molecular events, others may be amenable to pharmacological interpositions and therefore be exploitable in the context of HSC rejuvenation