Restoring bone marrow niche function rejuvenates aged hematopoietic stem cells by reactivating the DNA Damage Response.

ABSTRACT: Aging associated defects within stem cell-supportive niches contribute towards age-related decline in stem cell activity. However, mechanisms underlying age-related niche defects, and whether restoring niche function can improve stem cell fitness, remain unclear. Here, we sought to determine whether aged blood stem cell function can be restored by rejuvenating their supportive niches within the bone marrow (BM). We identify Netrin-1 as a critical regulator of BM niche cell aging. Niche-specific deletion of Netrin-1 induces premature aging phenotypes within the BM microenvironment, while supplementation of aged mice with Netrin-1 rejuvenates aged niche cells and restores competitive fitness of aged blood stem cells to youthful levels. We show that Netrin-1 plays an essential role in maintai

SUBMITTER: Ramalingam P 

PROVIDER: S-EPMC10086043 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature