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.
摘要:
衰老是由时间相关的细胞和功能损伤决定的生物学过程。导致生物体的生活水平下降。最近,老龄化调查取得了前所未有的进展,特别是检测到衰老速率至少在一定程度上通过进化保留的遗传途径和生物过程进行调节。造血干细胞(HSC)在生物体的整个生命周期内维持血液生成。衰老过程影响HSC的许多自然特征,导致他们的能力下降,独立于他们的微环境。新的研究表明,HSC对年龄依赖性应激敏感,随着衰老逐渐失去自我更新和再生潜力。microRNAs(miRNAs)是短的,转录后抑制翻译或通过序列特定连接刺激靶转录物的靶mRNA切割的非编码RNA。miRNA控制各种生物途径和过程,如衰老。一些miRNA在衰老中差异表达,引起人们对它们用作衰老过程的调节剂的担忧。miRNA在HSC的控制中起重要作用,并且还可以调节与特定细胞类型中的组织衰老相关的过程。在这次审查中,我们展示了年龄依赖性改变的贡献,包括DNA损伤,表观遗传景观,新陈代谢,和外在因素,影响HSC在衰老过程中的功能。此外,我们研究了调节HSCs衰老和年龄相关疾病的特定miRNA。视频摘要。