Decline in IGF1 in the bone marrow microenvironment initiates hematopoietic stem cell aging.

Aging Animals Bone Marrow Cross-Sectional Studies Hematopoiesis Hematopoietic Stem Cells Mice Stem Cell Niche
IGF1 aging healthspan hematopoiesis hematopoietic stem cell lineage bias metabolism microenvironment middle age niche

Journal

Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472

Informations de publication

Date de publication:
05 08 2021
Historique:
received: 16 07 2020
revised: 19 01 2021
accepted: 22 03 2021
pubmed: 14 4 2021
medline: 24 9 2021
entrez: 13 4 2021
Statut: ppublish

Résumé

Decline in hematopoietic stem cell (HSC) function with age underlies limited health span of our blood and immune systems. In order to preserve health into older age, it is necessary to understand the nature and timing of initiating events that cause HSC aging. By performing a cross-sectional study in mice, we discover that hallmarks of aging in HSCs and hematopoiesis begin to accumulate by middle age and that the bone marrow (BM) microenvironment at middle age induces and is indispensable for hematopoietic aging. Using unbiased approaches, we find that decreased levels of the longevity-associated molecule IGF1 in the local middle-aged BM microenvironment are a factor causing HSC aging. Direct stimulation of middle-aged HSCs with IGF1 rescues molecular and functional hallmarks of aging, including restored mitochondrial activity. Thus, although decline in IGF1 supports longevity, our work indicates that this also compromises HSC function and limits hematopoietic health span.

Identifiants

DOI: 10.1016/j.stem.2021.03.017 PMID: 33848471 PMC: PMC8349778
pubmed: 33848471
pii: S1934-5909(21)00123-5
doi: 10.1016/j.stem.2021.03.017
pmc: PMC8349778
mid: NIHMS1689317
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1473-1482.e7

Subventions

Organisme : NIA NIH HHS
ID : P30 AG038070
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK121062
Pays : United States
Organisme : NICHD NIH HHS
ID : T32 HD007065
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA034196
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL151654
Pays : United States
Organisme : NIDDK NIH HHS
ID : R56 DK112947
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK118072
Pays : United States

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests J.J.T. holds a sponsored research project with H3 Biomedicine.

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Auteurs

Kira Young (K)

The Jackson Laboratory, Bar Harbor, ME, USA.

Elizabeth Eudy (E)

The Jackson Laboratory, Bar Harbor, ME, USA.

Rebecca Bell (R)

The Jackson Laboratory, Bar Harbor, ME, USA.

Matthew A Loberg (MA)

The Jackson Laboratory, Bar Harbor, ME, USA.

Tim Stearns (T)

The Jackson Laboratory, Bar Harbor, ME, USA.

Devyani Sharma (D)

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Lars Velten (L)

Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Universitat Pompeu Fabra (UPF), Barcelona, Spain.

Simon Haas (S)

Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany; Berlin Institute of Health (BIH), Charité-Universitätsmedizin, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.

Marie-Dominique Filippi (MD)

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Jennifer J Trowbridge (JJ)

The Jackson Laboratory, Bar Harbor, ME, USA. Electronic address: jennifer.trowbridge@jax.org.

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Vieillissement › Decline in IGF1 in the bone marrow...
questionsmedicales.fr › Eucaryotes › Animaux › Decline in IGF1 in the bone marrow...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Moelle osseuse › Decline in IGF1 in the bone marrow...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études transversales › Decline in IGF1 in the bone marrow...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiogiques du sang › Hématopoïèse › Decline in IGF1 in the bone marrow...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système hématopoïétique › Cellules de la moelle osseuse › Cellules souches hématopoïétiques › Decline in IGF1 in the bone marrow...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Decline in IGF1 in the bone marrow...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Niche de cellules souches › Decline in IGF1 in the bone marrow...