% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Dellorusso:294551,
author = {P. V. Dellorusso and M. A. Proven and F. J. Calero-Nieto
and X. Wang and C. A. Mitchell and F. Hartmann$^*$ and M.
Amouzgar and P. Favaro and A. DeVilbiss and J. W. Swann and
T. T. Ho and Z. Zhao and S. C. Bendall and S. Morrison and
B. Göttgens and E. Passegué},
title = {{A}utophagy counters inflammation-driven glycolytic
impairment in aging hematopoietic stem cells.},
journal = {Cell stem cell},
volume = {31},
number = {7},
issn = {1934-5909},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2024-02326},
pages = {1020 - 1037.e9},
year = {2024},
abstract = {Autophagy 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.},
keywords = {Animals / Autophagy / Hematopoietic Stem Cells: metabolism
/ Inflammation: pathology / Inflammation: metabolism /
Glycolysis / Mice / Mice, Inbred C57BL / Aging: pathology /
Aging: metabolism / Cellular Senescence / Signal
Transduction / Suppressor of Cytokine Signaling 3 Protein:
metabolism / Glucose: metabolism / aging (Other) / autophagy
(Other) / hematopoietic stem cells (Other) / inflammation
(Other) / metabolism (Other) / regeneration (Other) /
Suppressor of Cytokine Signaling 3 Protein (NLM Chemicals) /
Glucose (NLM Chemicals)},
ddc = {570},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38754428},
pmc = {pmc:PMC11350610},
doi = {10.1016/j.stem.2024.04.020},
url = {https://inrepo02.dkfz.de/record/294551},
}