TY - JOUR
T1 - Aged hematopoietic stem cells are refractory to bloodborne systemic rejuvenation interventions
AU - Ho, Theodore T.
AU - Dellorusso, Paul V.
AU - Verovskaya, Evgenia V.
AU - Bakker, Sietske T.
AU - Flach, Johanna
AU - Smith, Lucas K.
AU - Ventura, Patrick B.
AU - Lansinger, Olivia M.
AU - Hérault, Aurélie
AU - Zhang, Si Yi
AU - Kang, Yoon A.
AU - Mitchell, Carl A.
AU - Villeda, Saul A.
AU - Passegué, Emmanuelle
N1 - Publisher Copyright:
© 2021 Ho et al.
PY - 2021/5/25
Y1 - 2021/5/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85106890077&partnerID=8YFLogxK
U2 - 10.1084/jem.20210223
DO - 10.1084/jem.20210223
M3 - Article
C2 - 34032859
AN - SCOPUS:85106890077
SN - 0022-1007
VL - 218
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 7
M1 - e20210223
ER -