Aging and Cancer Group

BIOMEDICAL RESEARCH

Mate Maus

Group Leader

Biosketch

We study how aging-driven metabolic bottlenecks create cancer-permissive microenvironments — and how to reprogram them.

Our work focuses on two contexts: physiological aging and therapy-accelerated aging in cancer survivors. In both settings, tissues undergo persistent metabolic alterations that redistribute and limit key metabolites, reshaping cellular fitness and potentially enabling malignant initiation and recurrence.

A prominent example of such bottlenecks is the redistribution of iron during aging, illustrating how resource availability within tissues can become distorted. More broadly, we investigate how aging-driven metabolic constraints arise locally or systemically and how they alter cancer permissiveness.

To address these questions, we integrate analyses of patient material in close collaboration with clinicians, mouse models of aging and cancer survivorship, organoid and cellular systems in vitro, and bioinformatic interrogation of large human cohorts. Across these platforms, we examine how metabolic bottlenecks emerge, whether they are tissue-intrinsic or systemically imposed, and how they influence cancer risk, particularly in the colon and bone marrow.

Our long-term goal is to identify and therapeutically relieve aging-driven metabolic bottlenecks to restore tissue resilience and reduce cancer risk.

Figure: DAB enhanced iron staining in cancerous and adjacent tissues of a colorectal cancer patient.

Research Lines

Map aging-driven metabolic bottlenecks across tissues.
We aim to systematically identify metabolic bottlenecks that emerge during physiological aging and therapy-accelerated aging in cancer survivors. By integrating patient material, in vivo models, and large-scale cohort analyses, we will define where and how resource constraints arise, whether locally or systemically, and how they differ between tissues such as the colon and bone marrow.
Define how metabolic bottlenecks reshape cellular fitness and anti-tumor immunity
We seek to understand how aging-induced metabolic constraints alter cellular competition, differentiation trajectories, and immune surveillance. Our goal is to uncover the drivers that render tissues cancer-permissive and to distinguish transient adaptations from persistent alterations that sustain risk.
Develop diagnostics and interventions to relieve aging-driven metabolic constraints
Building on mechanistic insights, we aim to translate identified bottlenecks into biomarkers of cancer-permissive aging and therapeutic strategies that restore tissue resilience. Our long-term objective is to enable risk stratification and targeted metabolic reprogramming to reduce cancer incidence and recurrence in aging populations and cancer survivors.

Team

Group Leader

Mate Maus

PhD Students

Francesca Cogo

Marc Guasch

Ning Huang

Jie Yang

Medical Postdoctoral Fellow

Adelina Silvana Gheorghe

Publications

“My Bibliography” at the NCBI

Amengual J, Alay A, Vaquero J, Gonzalez-Sanchez E, Bertran E, Sánchez A, Herrera B, Meyer K, Maus M, Serrano M, Martínez-Chantar ML, Fabregat I. Iron chelation as a new therapeutic approach to prevent senescence and liver fibrosis progression. Cell Death Dis. 2024 Sep 17;15(9):680. doi: 10.1038/s41419-024-07063-0.
López-Polo V, Maus M, Zacharioudakis E, Lafarga M, Attolini CS, Marques FDM, Kovatcheva M, Gavathiotis E, Serrano M. Release of mitochondrial dsRNA into the cytosol is a key driver of the inflammatory phenotype of senescent cells. Nat Commun. 2024 Aug 27;15(1):7378. doi: 10.1038/s41467-024-51363-0.
Maus M, López-Polo V, Mateo L, Lafarga M, Aguilera M, De Lama E, Meyer K, Sola A, Lopez-Martinez C, López-Alonso I, Guasch-Piqueras M, Hernandez-Gonzalez F, Chaib S, Rovira M, Sanchez M, Faner R, Agusti A, Diéguez-Hurtado R, Ortega S, Manonelles A, Engelhardt S, Monteiro F, Stephan-Otto Attolini C, Prats N, Albaiceta G, Cruzado JM, Serrano M. Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype. Nat Metab. 2023 Dec;5(12):2111-2130.
Maus M, López-Polo V, Lafarga M, Aguilera M, De Lama E, Meyer K, Manonelles A, Sola A, Lopez Martinez C, López-Alonso I, Hernandez-Gonzales F, Chaib S, Rovira M, Sanchez M, Faner R, Agusti A, Prats N, Albaiceta G, Cruzado JM, Serrano M. Iron accumulation drives fibrosis, senescence, and the senescence-associated secretory phenotype. bioRxiv 2022 https://doi.org/10.1101/2022.07.29.501953
Rovira M, […], Maus M, […], Serrano M. (2022) The lysosomal proteome of senescent cells contributes to the senescence secretome. Aging Cell. 2022 Oct;21(10):e13707
Maus M, Serrano M. A novel redox cycle diverts cells from oncogene-induced senescence into cancer. Mol Cell. 2021 Sep 16;81(18):3672-3674.
Kahlfuss S, Kaufmann U, Concepcion AR, Noyer L, Raphael D, Vaeth M, Yang J, Pancholi P, Maus M, Muller J, Kozhaya L, Khodadadi-Jamayran A, Sun Z, Shaw P, Unutmaz D, Stathopulos PB, Feist C, Cameron SB, Turvey SE, Feske S. STIM1-mediated calcium influx controls antifungal immunity and the metabolic function of non-pathogenic Th17 cells. EMBO Mol Med. 2020 Aug 7;12(8):e11592.
Saint Fleur-Lominy S* and Maus M*, Vaeth M, Lange I, Zee I, Suh D, Liu C, Wu X, Tikhonova A, Aifantis I, Feske S. STIM1 and STIM2 Mediate Cancer-Induced Inflammation in T Cell Acute Lymphoblastic Leukemia. Cell Rep. 2018 Sep 11;24(11):3045-3060.e5. (*equal contribution)
Vaeth M* and Maus M*, Klein-Hessling S, Freinkman E, Yang J, Eckstein M, Cameron S, Turvey SE, Serfling E, Berberich-Siebelt F, Possemato R, Feske S. Store-Operated Ca2+ Entry Controls Clonal Expansion of T Cells through Metabolic Reprogramming. Immunity. 2017 Oct 17;47(4):664-679.e6. (*equal contribution)
Maus M, Cuk M, Patel B, Lian J, Ouimet M, Kaufmann U, Yang J, Horvath R, Hornig-Do HT, Chrzanowska-Lightowlers ZM, Moore KJ, Cuervo AM, Feske S. Store-Operated Ca2+ Entry Controls Induction of Lipolysis and the Transcriptional Reprogramming to Lipid Metabolism. Cell Metab. 2017 Mar 7;25(3):698-712.
Vaeth M, Zee I, Concepcion AR, Maus M, Shaw P, Portal-Celhay C, Zahra A, Kozhaya L, Weidinger C, Philips J, Unutmaz D, Feske S. Ca2+ Signaling but Not Store-Operated Ca2+ Entry Is Required for the Function of Macrophages and Dendritic Cells. J Immunol. 2015 Aug 1;195(3):1202-17.
Maus M, Jairaman A, Stathopulos PB, Muik M, Fahrner M, Weidinger C, Benson M, Fuchs S, Ehl S, Romanin C, Ikura M, Prakriya M, Feske S. Missense mutation in immunodeficient patients shows the multifunctional roles of coiled-coil domain 3 (CC3) in STIM1 activation. Proc Natl Acad Sci U S A. 2015 May 12;112(19):6206-11.
Maus M, Medgyesi D, Kiss E, Schneider AE, Enyedi A, Szilágyi N, Matkó J, Sármay G. B cell receptor-induced Ca2+ mobilization mediates F-actin rearrangements and is indispensable for adhesion and spreading of B lymphocytes. J Leukoc Biol. 2013 Apr;93(4):537-47.
Maus M, Medgyesi D, Kövesdi D, Csuka D, Koncz G, Sármay G. Grb2 associated binder 2 couples B-cell receptor to cell survival. Cell Signal. 2009 Feb;21(2):220-7.
Sármay G, Angyal A, Kertész A, Maus M, Medgyesi D. The multiple function of Grb2 associated binder (Gab) adaptor/scaffolding protein in immune cell signaling. Immunol Lett. 2006 Apr 15;104(1-2):76-82.

Projects

This group is supported by the ”la Caixa” Foundation – CaixaResearch.
Ayudas para contratos Ramón y Cajal (RYC) (REF: RYC2020-030652-I).
José Baselga Innovative Disruption Program (Astra Zeneca Foundation; REF: 10050754).
Generacion de Conocimiento (Spanish Ministry of Science; REF: PID2022-142205OB-I00).
La Caixa Hub Innovation Award.
XXVIII Fundacion FERO grant; (FERO Foundation; REF: BFERO2024.03)
Title: Understanding and translating the connection between age-associated iron dyshomeostasis and myeloproliferative neoplasms in the elderly (MYELOIRONAGE). Funding entity: Agencia Estatal de Investigación – Ministerio de Ciencia e Innovación. Ref: PID2022-142205OB-I00. Duration: 01/09/2023 – 31/08/2027. PI: Mate Maus.