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Elderly human hematopoietic progenitor cells express cellular senescence markers and are more susceptible to pyroptosis
Tinhinane Fali, … , Delphine Sauce, Victor Appay
Tinhinane Fali, … , Delphine Sauce, Victor Appay
Published July 12, 2018
Citation Information: JCI Insight. 2018;3(13):e95319. https://doi.org/10.1172/jci.insight.95319.
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Research Article Aging Stem cells

Elderly human hematopoietic progenitor cells express cellular senescence markers and are more susceptible to pyroptosis

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Abstract

The maintenance of effective immunity over time is dependent on the capacity of hematopoietic stem cells (HSCs) to sustain the pool of immunocompetent mature cells. Decline of immune competence with old age may stem from HSC defects, including reduced self-renewal potential and impaired lymphopoiesis, as suggested in murine models. To obtain further insights into aging-related alteration of hematopoiesis, we performed a comprehensive study of blood hematopoietic progenitor cells (HPCs) from older humans. In the elderly, HPCs present active oxidative phosphorylation and are pressed to enter cell cycling. However, p53-p21 and p15 cell senescence pathways, associated with telomerase activity deficiency, strong telomere attrition, and oxidative stress, are engaged, thus limiting cell cycling. Moreover, survival of old HPCs is impacted by pyroptosis, an inflammatory form of programmed cell death. Lastly, telomerase activity deficiency and telomere length attrition of old HPCs may be passed on to progeny cells such as naive T lymphocytes, further highlighting the poor hematopoietic potential of the elderly. This pre-senescent profile is characteristic of the multiple intrinsic and extrinsic factors affecting HPCs in elderly individuals and represents a major obstacle in terms of immune reconstitution and efficacy with advanced age.

Authors

Tinhinane Fali, Véronique Fabre-Mersseman, Takuya Yamamoto, Charles Bayard, Laura Papagno, Solène Fastenackels, Rima Zoorab, Richard A. Koup, Jacques Boddaert, Delphine Sauce, Victor Appay

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Figure 6

Associations between circulating HPCs and naive CD4+ or CD8+ T cell properties.

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Associations between circulating HPCs and naive CD4+ or CD8+ T cell prop...
(A) Correlations between CLP and naive CD4+ or CD8+ T cell ex vivo absolute counts. (B) Telomere length (top panels) and relative telomerase activity (bottom panels) in naive or senescent CD57+ memory CD4+ or CD8+ T cells FACS isolated from young (Y, n = 9), middle-aged (M, n = 15), or old (O, n = 14) healthy adult PBMCs. (C) Correlations between CLP and naive CD4+ or CD8+ T cell telomere length or telomerase activity. The Mann-Whitney test was used for comparisons. Bars indicate the median. Spearman’s rank test was used to determine correlations.

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