Aging of haematopoietic stem cells : Causes, consequences and future perspectives Volume 27, issue 5, Septembre-Octobre 2021


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Inserm U976 Équipe 5, Institut de Recherche Saint Louis, Université de Paris, Hôpital Saint Louis, France
* Tirés à part

Haematopoietic stem cells (HSCs) occupy the apex of the haematopoietic system, and ensure the renewal of all mature blood cells throughout life. Studies in both mice and humans have demonstrated that the functional properties of HSCs change with age, altering their capacity to reconstitute the haematopoietic system, and diminishing their lymphoid differentiation potential, giving rise to a myeloid-biased haematopoiesis in aged individuals. A range of different events are now known to contribute to the decline of HSC function observed with age, including alterations within the HSC themselves, as well as changes occurring in the bone marrow microenvironment where HSC reside. Cell intrinsic changes include the accumulation of DNA damage and telomere erosion, as well as alterations in HSC metabolism which trigger stress-response mechanisms and cellular exhaustion. More recently, age-associated changes in the epigenetic state have also been implicated as an important driver of HSC functional decline. Within the bone marrow microenvironment, the onset of low-level chronic inflammation and remodelling of HSC niches which take place with age also influence HSC functional capacity and contribute to a myeloid-biased differentiation. HSC aging has important downstream consequences for the health of the elderly, contributing to the chronic inflammatory state and decline in adaptive immune function observed in aged individuals, and predisposing to the onset of myeloid malignancies. Understanding the mechanisms driving HSC aging has suggested numerous therapeutic strategies to rejuvenate HSC function, which have shown promising results in aging mice.