Open AccessAged hematopoietic stem cells are refractory to bloodborne systemic rejuvenation interventions
Author(s) -
Theodore Ho,
Paul Dellorusso,
Evgenia Verovskaya,
Sietske T. Bakker,
Johanna Flach,
Lucas K. Smith,
Patrick Ventura,
Olivia Lansinger,
Aurélie Herault,
Si Yi Zhang,
Yoon-A Kang,
Carl A. Mitchell,
Saul Villeda,
Emmanuelle Passegué
Publication year - 2021
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20210223
Subject(s) - parabiosis , haematopoiesis , stem cell , bone marrow , biology , calorie restriction , rejuvenation , transplantation , progenitor cell , immunology , microbiology and biotechnology , medicine , genetics , endocrinology
While young blood can restore many aged tissues, its effects on the aged blood system itself and old hematopoietic stem cells (HSCs) have not been determined. Here, we used transplantation, parabiosis, plasma transfer, exercise, calorie restriction, and aging mutant mice to understand the effects of age-regulated systemic factors on HSCs and their bone marrow (BM) niche. We found that neither exposure to young blood, nor long-term residence in young niches after parabiont separation, nor direct heterochronic transplantation had any observable rejuvenating effects on old HSCs. Likewise, exercise and calorie restriction did not improve old HSC function, nor old BM niches. Conversely, young HSCs were not affected by systemic pro-aging conditions, and HSC function was not impacted by mutations influencing organismal aging in established long-lived or progeroid genetic models. Therefore, the blood system that carries factors with either rejuvenating or pro-aging properties for many other tissues is itself refractory to those factors.