000294448 001__ 294448
000294448 005__ 20241114100503.0
000294448 0247_ $$2doi$$adoi: 10.1016/j.stem.2024.04.020. 
000294448 037__ $$aDKFZ-2024-02273
000294448 041__ $$aEnglish
000294448 1001_ $$aDellorusso 1 , Paul V.$$b0
000294448 245__ $$aAutophagy counters inflammation-driven glycolytic impairment in aging hematopoietic stem cells
000294448 260__ $$c2024
000294448 3367_ $$2DRIVER$$aarticle
000294448 3367_ $$2DataCite$$aOutput Types/Journal article
000294448 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1731573228_11872
000294448 3367_ $$2BibTeX$$aARTICLE
000294448 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000294448 3367_ $$00$$2EndNote$$aJournal Article
000294448 520__ $$aAutophagy is central to the benefits of longevity signaling programs and to hematopoietic stem cell (HSC) response to nutrient stress. With age, a subset of HSCs increases autophagy flux and preserves regenerative capacity, but the signals triggering autophagy and maintaining the functionality of autophagy-activated old HSCs (oHSCs) remain unknown. Here, we demonstrate that autophagy is an adaptive cytoprotective response to chronic inflammation in the aging murine bone marrow (BM) niche. We find that inflammation impairs glucose uptake and suppresses glycolysis in oHSCs through Socs3-mediated inhibition of AKT/FoxO-dependent signaling, with inflammation-mediated autophagy engagement preserving functional quiescence by enabling metabolic adaptation to glycolytic impairment. Moreover, we show that transient autophagy induction via a short-term fasting/refeeding paradigm normalizes glycolytic flux and significantly boosts oHSC regenerative potential. Our results identify inflammation-driven glucose hypometabolism as a key driver of HSC dysfunction with age and establish autophagy as a targetable node to reset oHSC regenerative capacity.
000294448 7001_ $$aProven 1 , Melissa A.$$b1
000294448 7001_ $$aCalero-Nieto , Fernando J.$$b2
000294448 7001_ $$a, Xiaonan Wang$$b3
000294448 7001_ $$aMitchell , Carl A.$$b4
000294448 7001_ $$a, Felix Hartmann$$b5
000294448 7001_ $$a, Meelad Amouzgar$$b6
000294448 7001_ $$a, Patricia Favaro$$b7
000294448 7001_ $$a, Andrew DeVilbiss$$b8
000294448 7001_ $$aSwann , James W.$$b9
000294448 7001_ $$aHo , Theodore T.$$b10
000294448 7001_ $$a, Zhiyu Zhao$$b11
000294448 7001_ $$aBendall , Sean C.$$b12
000294448 7001_ $$a, Sean Morrison$$b13
000294448 7001_ $$a, Berthold Göttgens$$b14
000294448 7001_ $$a, Emmanuelle Passegué 1 7$$b15
000294448 773__ $$adoi: 10.1016/j.stem.2024.04.020. $$n7$$p1020-1037$$tCell stem cell$$v31$$y2024
000294448 8564_ $$uhttps://www.sciencedirect.com/science/article/pii/S1934590924001747?via%3Dihub
000294448 8564_ $$uhttps://inrepo02.dkfz.de/record/294448/files/1-s2.0-S1934590924001747-main.pdf$$yRestricted
000294448 8564_ $$uhttps://inrepo02.dkfz.de/record/294448/files/1-s2.0-S1934590924001747-main.pdf?subformat=pdfa$$xpdfa$$yRestricted
000294448 9201_ $$0I:(DE-He78)D260-20160331$$kD260$$lNWG Systemimmunologie und Einzelzell-Biologie$$x0
000294448 980__ $$ajournal
000294448 980__ $$aTEMPENTRY
000294448 980__ $$aVDBRELEVANT
000294448 980__ $$aI:(DE-He78)D260-20160331