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

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Item Type:	Article
Title:	Decline in IGF1 in the bone marrow microenvironment initiates hematopoietic stem cell aging
Creators Name:	Young, K., Eudy, E., Bell, R., Loberg, M.A., Stearns, T., Sharma, D., Velten, L., Haas, S., Filippi, M.D. and Trowbridge, J.J.
Abstract:	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.
Keywords:	Hematopoietic Stem Cell, Hematopoiesis, Aging, Healthspan, IGF1, Lineage Bias, Metabolism, Microenvironment, Niche, Middle Age, Animals, Mice
Source:	Cell Stem Cell
ISSN:	1934-5909
Publisher:	Cell Press
Volume:	28
Number:	8
Page Range:	1473-1482
Date:	5 August 2021
Additional Information:	Copyright © 2021 Elsevier Inc.
Official Publication:	https://doi.org/10.1016/j.stem.2021.03.017
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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