TY  - JOUR
AB  - Somatic stem cell pools comprise diverse, highly specialized subsets whose individual contribution is critical for the overall regenerative function. In the bone marrow, myeloid-biased hematopoietic stem cells (myHSCs) are indispensable for replenishment of myeloid cells and platelets during inflammatory response but, at the same time, become irreversibly damaged during inflammation and aging. Here we identify an extrinsic factor, semaphorin 4A (Sema4A), which non-cell-autonomously confers myHSC resilience to inflammatory stress. We show that, in the absence of Sema4A, myHSC inflammatory hyper-responsiveness in young mice drives excessive myHSC expansion, myeloid bias and profound loss of regenerative function with age. Mechanistically, Sema4A is mainly produced by neutrophils, signals via a cell surface receptor, plexin D1, and safeguards the myHSC epigenetic state. Our study shows that, by selectively protecting a distinct stem cell subset, an extrinsic factor preserves functional diversity of somatic stem cell pool throughout organismal lifespan.
AU  - Toghani, D.*
AU  - Gupte, S.C.*
AU  - Zeng, S.*
AU  - Mahammadov, E.
AU  - Crosse, E.I.*
AU  - Seyedhassantehrani, N.*
AU  - Burns, C.*
AU  - Gravano, D.*
AU  - Radtke, S.*
AU  - Kiem, H.P.*
AU  - Rodriguez, S.*
AU  - Carlesso, N.*
AU  - Pradeep, A.*
AU  - Georgiades, A.*
AU  - Lucas, F.*
AU  - Wilson, N.K.*
AU  - Kinston, S.J.*
AU  - Göttgens, B.*
AU  - Zong, L.*
AU  - Beerman, I.*
AU  - Park, B.*
AU  - Janssens, D.H.*
AU  - Jones, D.*
AU  - Toghani, A.*
AU  - Nerlov, C.*
AU  - Pietras, E.M.*
AU  - Mesnieres, M.*
AU  - Maes, C.*
AU  - Kumanogoh, A.*
AU  - Worzfeld, T.*
AU  - Cheong, J.G.*
AU  - Josefowicz, S.Z.*
AU  - Kharchenko, P.V.*
AU  - Scadden, D.T.*
AU  - Scialdone, A.
AU  - Spencer, J.A.*
AU  - Silberstein, L.*
C1  - 73231
C2  - 56960
CY  - Campus, 4 Crinan St, London, N1 9xw, England
TI  - Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells.
JO  - Nature Aging
PB  - Springernature
PY  - 2025
SN  - 2662-8465
ER  - 

TY  - JOUR
AB  - Correction to: Nature Aginghttps://doi.org/10.1038/s43587-024-00798-7, published online 29 January 2025. In the version of the article initially published, there were some errors in the order of the reference list which have now been amended in the HTML and PDF versions of the article.
AU  - Toghani, D.*
AU  - Gupte, S.C.*
AU  - Zeng, S.*
AU  - Mahammadov, E.
AU  - Crosse, E.I.*
AU  - Seyedhassantehrani, N.*
AU  - Burns, C.*
AU  - Gravano, D.*
AU  - Radtke, S.*
AU  - Kiem, H.P.*
AU  - Rodriguez, S.*
AU  - Carlesso, N.*
AU  - Pradeep, A.*
AU  - Georgiades, A.*
AU  - Lucas, F.*
AU  - Wilson, N.K.*
AU  - Kinston, S.J.*
AU  - Göttgens, B.*
AU  - Zong, L.*
AU  - Beerman, I.*
AU  - Park, B.*
AU  - Janssens, D.H.*
AU  - Jones, D.*
AU  - Toghani, A.*
AU  - Nerlov, C.*
AU  - Pietras, E.M.*
AU  - Mesnieres, M.*
AU  - Maes, C.*
AU  - Kumanogoh, A.*
AU  - Worzfeld, T.*
AU  - Cheong, J.G.*
AU  - Josefowicz, S.Z.*
AU  - Kharchenko, P.V.*
AU  - Scadden, D.T.*
AU  - Scialdone, A.
AU  - Spencer, J.A.*
AU  - Silberstein, L.*
C1  - 73439
C2  - 56840
CY  - Campus, 4 Crinan St, London, N1 9xw, England
TI  - Author Correction: Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells.
JO  - Nature Aging
VL  - 5
IS  - 4
PB  - Springernature
PY  - 2025
SN  - 2662-8465
ER  - 

TY  - JOUR
AB  - Despite the manifestation and contribution of cellular senescence to aging and various diseases, accurate identification of heterogeneous senescent cells remains challenging. Current senescence evaluation methods rely mainly on limited markers or homogeneous samples, which might fail to capture universal senescence features, limiting their generalizability. Here we developed the human universal senescence index (hUSI), an accurate and robust senescence evaluation method for diverse cells and samples. Based on features learned from the most comprehensive cellular senescence-associated transcriptome data so far, hUSI demonstrated its convincing connections with senescence phenotypes and superior robustness in predicting senescence state. Using hUSI, we discovered potential senescence regulators and mapped senescent cell accumulation across cell types in coronavirus disease 2019 (COVID-19). The method also facilitates decoding heterogeneous senescence states in melanoma tumors, identifying prognosis-associated signaling pathways. Overall, hUSI demonstrates its utility in characterizing cellular senescence across biological contexts, with broad applications in aging research and clinical practice.
AU  - Wang, J.*
AU  - Zhou, X.*
AU  - Yu, P.*
AU  - Yao, J.*
AU  - Guo, P.*
AU  - Xu, Q.*
AU  - Zhao, Y.*
AU  - Wang, G.*
AU  - Li, Q.*
AU  - Zhu, X.*
AU  - Wei, G.W.*
AU  - Wang, W.
AU  - Ni, T.*
C1  - 74844
C2  - 57604
CY  - Campus, 4 Crinan St, London, N1 9xw, England
TI  - A transcriptome-based human universal senescence index (hUSI) robustly predicts cellular senescence under various conditions.
JO  - Nature Aging
PB  - Springernature
PY  - 2025
SN  - 2662-8465
ER  - 

TY  - JOUR
AB  - Age-related decline in brain endothelial cell (BEC) function contributes critically to neurological disease. Comprehensive atlases of the BEC transcriptome have become available, but results from proteomic profiling are lacking. To gain insights into endothelial pathways affected by aging, we developed a magnetic-activated cell sorting-based mouse BEC enrichment protocol compatible with proteomics and resolved the profiles of protein abundance changes during aging. Unsupervised cluster analysis revealed a segregation of age-related protein dynamics with biological functions, including a downregulation of vesicle-mediated transport. We found a dysregulation of key regulators of endocytosis and receptor recycling (most prominently Arf6), macropinocytosis and lysosomal degradation. In gene deletion and overexpression experiments, Arf6 affected endocytosis pathways in endothelial cells. Our approach uncovered changes not picked up by transcriptomic studies, such as accumulation of vesicle cargo and receptor ligands, including Apoe. Proteomic analysis of BECs from Apoe-deficient mice revealed a signature of accelerated aging. Our findings provide a resource for analysing BEC function during aging.
AU  - Todorov-Völgyi, K.*
AU  - González-Gallego, J.*
AU  - Müller, S.A.*
AU  - Beaufort, N.*
AU  - Malik, R.*
AU  - Schifferer, M.*
AU  - Todorov, M.I.
AU  - Crusius, D.*
AU  - Robinson, S.*
AU  - Schmidt, A.*
AU  - Körbelin, J.*
AU  - Bareyre, F.*
AU  - Ertürk, A.
AU  - Haass, C.*
AU  - Simons, M.*
AU  - Paquet, D.*
AU  - Lichtenthaler, S.F.*
AU  - Dichgans, M.*
C1  - 70295
C2  - 55492
CY  - Campus, 4 Crinan St, London, N1 9xw, England
SP  - 595-612
TI  - Proteomics of mouse brain endothelium uncovers dysregulation of vesicular transport pathways during aging.
JO  - Nature Aging
VL  - 4
IS  - 4
PB  - Springernature
PY  - 2024
SN  - 2662-8465
ER  - 

TY  - JOUR
AB  - Type 2 diabetes mellitus (T2D) presents a major health and economic burden that could be alleviated with improved early prediction and intervention. While standard risk factors have shown good predictive performance, we show that the use of blood-based DNA methylation information leads to a significant improvement in the prediction of 10-year T2D incidence risk. Previous studies have been largely constrained by linear assumptions, the use of cytosine-guanine pairs one-at-a-time and binary outcomes. We present a flexible approach (via an R package, MethylPipeR) based on a range of linear and tree-ensemble models that incorporate time-to-event data for prediction. Using the Generation Scotland cohort (training set ncases = 374, ncontrols = 9,461; test set ncases = 252, ncontrols = 4,526) our best-performing model (area under the receiver operating characteristic curve (AUC) = 0.872, area under the precision-recall curve (PRAUC) = 0.302) showed notable improvement in 10-year onset prediction beyond standard risk factors (AUC = 0.839, precision-recall AUC = 0.227). Replication was observed in the German-based KORA study (n = 1,451, ncases = 142, P = 1.6 × 10-5).
AU  - Cheng, Y.*
AU  - Gadd, D.A.*
AU  - Gieger, C.
AU  - Monterrubio-Gómez, K.*
AU  - Zhang, Y.*
AU  - Berta, I.*
AU  - Stam, M.J.*
AU  - Szlachetka, N.*
AU  - Lobzaev, E.*
AU  - Wrobel, N.*
AU  - Murphy, L.*
AU  - Campbell, A.*
AU  - Nangle, C.*
AU  - Walker, R.M.*
AU  - Fawns-Ritchie, C.*
AU  - Peters, A.
AU  - Rathmann, W.*
AU  - Porteous, D.J.*
AU  - Evans, K.L.*
AU  - McIntosh, A.M.*
AU  - Cannings, T.I.*
AU  - Waldenberger, M.
AU  - Ganna, A.*
AU  - McCartney, D.L.*
AU  - Vallejos, C.A.*
AU  - Marioni, R.E.*
C1  - 67785
C2  - 54263
CY  - Campus, 4 Crinan St, London, N1 9xw, England
SP  - 450-458
TI  - Development and validation of DNA methylation scores in two European cohorts augment 10-year risk prediction of type 2 diabetes.
JO  - Nature Aging
VL  - 3
IS  - 4
PB  - Springernature
PY  - 2023
SN  - 2662-8465
ER  -