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

Document Type

Article

Publication Date

8-5-2021

Publication Title

Cell Stem Cell

Keywords

JMG, Aging, Animals, Bone Marrow, Cross-Sectional Studies, Hematopoiesis, Hematopoietic Stem Cells, Mice, Stem Cell Niche

JAX Source

Cell Stem Cell 2021 Aug 5; 28(8):1473-1482.e7

Volume

28

Issue

8

First Page

1473

Last Page

1482

ISSN

1875-9777

PMID

33848471

DOI

https://doi.org/10.1016/j.stem.2021.03.017

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.

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