The Maus Lab

🌱Excited to welcome Aistė Avižaitė from Lithuania’s
@VU_LT
to the lab this summer!

She’ll be studying how chemotherapy alters metabolism in healthy tissues and how this may drive accelerated aging in childhood cancer survivors.

#Aging #Cancer #SummerIntern

Implausibility of radical life extension in humans in the twenty-first century - Nature Aging In the twentieth century, human life expectancy rose dramatically. Based on the past three decades of observed mortality in the eight countries with the longest-lived populations and in Hong Kong and ...

200 years ago in Barcelona, your 40s meant preparing for death. Today, you might have 40 more years ahead.

But as @sjayolshansky et al. show, most gains came from reducing early death. Further progress depends on tackling aging and its consequences.
#JC

www.nature.com/articles/s43...

🌱 Welcome aboard, Laura!

Joining us this summer from @URV_universitat, Laura Boró García will be exploring how aging and chemotherapy disrupt metabolism and epigenetics in the bone marrow. We’re thrilled to have her with us! 🧬🧪

#Aging #Cancer #SummerIntern

Dietary restriction impacts health and lifespan of genetically diverse mice - Nature Health effects of dietary restriction are uncoupled from longevity.

Longer lives in laboratory conditions may compromise survival in the real world. In a large study on genetically diverse mice, Di Francesco et al. in Jackson Labs show that lifespan extension under caloric restriction doesn’t always improve health.

#JournalClub

www.nature.com/articles/s41...

Dietary restriction impacts health and lifespan of genetically diverse mice - Nature Health effects of dietary restriction are uncoupled from longevity.

Longer lives in laboratory conditions may compromise survival in the real world. In a large study on genetically diverse mice, @DiFrancescoA et al. in @jacksonlab show that lifespan extension under caloric restriction doesn’t always improve health.

#JournalClub
www.nature.com/articles/s41...

In a preprint, Han et al. from @yibinkang’s lab report that cancer cells in bone metastases hijack iron from bone marrow macrophages that normally support red blood cell production — linking anemia to metastatic progression.

#JournalClub

www.biorxiv.org/content/10.1...

What makes a bag of cells become a complex, intelligent being—and what breaks those rules to cause aging and system breakdown?

Donella Meadows’ Thinking in Systems offers a toolkit to understand biology, society, and the economy in their native language: systems.

#LabReads 📚

Apc-mutant cells act as supercompetitors in intestinal tumour initiation - Nature Using experiments in organoids and in vivo in mice, the authors show that Apc-mutant cells act as supercompetitors to initiate the formation of adenomas.

Intestinal stem cells (ISCs) with APC mutations outcompete wild-type ISCs by suppressing Wnt signaling in their neighbors - driving colorectal tumor formation.

Exciting work from Vermeulen lab!

Presented by Marc Guasch @JournalClub
www.nature.com/articles/s41...

Molecular characteristics and clinical implications of TP53 mutations in therapy-related myelodysplastic syndromes - Blood Cancer Journal Blood Cancer Journal - Molecular characteristics and clinical implications of TP53 mutations in therapy-related myelodysplastic syndromes

We are all born with blood cells that could turn into cancer. But aging and chemo don’t just damage cells—they differently pick the bad ones. Chemo favors TP53-mutant clones giving rise to therapy-related MDS.
#JournalClub Ning Huang
www.nature.com/articles/s41...

Iron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis - Scientific Reports Scientific Reports - Iron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis

Hereditary hemochromatosis related iron overload accelerates age-related cardiac hypertrophy in a mouse model.

Francesca Cogo #JournalClub

www.nature.com/articles/s41...

Increasing number of young individuals are being diagnosed with colorectal cancer. This week, we hosted medical oncologist Iosune Baraibar, who shared what she at
@vhio.bsky.social, and @danafarber.bsky.social collaborators are doing to understand and act on this epidemic. Honored to work at VHIO.

The geroprotectors trametinib and rapamycin combine additively to extend mouse healthspan and lifespan - Nature Aging Gkioni et al. show that trametinib, which targets the Ras–Mek–Erk pathway, extends lifespan in male and female mice and that co-treatment with the known geroprotector rapamycin additively extends life...

Cellular hypermetabolism drives aging and age-related disease. Gkioni et al. (Partridge lab) show that targeting two independent growth/metabolism regulators synergistically extends lifespan and delays cancer in aging mice.

Mate Maus #JournalClub
www.nature.com/articles/s43...

Defining Stem Cell Dynamics in Models of Intestinal Tumor Initiation Common genetic alterations during tumor initiation in the mouse gut reveal clonal advantages. [Also see Perspective by Bozic and Nowak]

For colon cells to form cancer, they must acquire mutations—but how do early mutant clones expand? Vermeulen et al. use lineage tracing to show that competition with wild-type cells is real, and chance dominates.

Marc Guasch #JournalClub

www.science.org/doi/10.1126/...

Cell competition promotes metastatic intestinal cancer through a multistage process Microenvironment; Cell biology; Cancer

Krotenberg et al. created fluorescent mixed organoids to study cell competition in colorectal cancer. They show cancer cells actively eliminate wild-type neighbors via JNK signaling to fuel their growth.

Marc Guasch #JournalClub
www.cell.com/iscience/ful...

🚀 Recently, we welcomed Agnese Brischetto as our #JournalClub invited speaker! She shared insights into the biology of psoriasis—an autoimmune skin condition affecting ~3% of the population—along with intriguing findings on potential new treatments.

Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice Bone marrow deficient in a gene frequently mutated in blood cells of elderly humans promotes atherosclerosis in mice.

Atherosclerotic burden drives age-related cardiovascular events. Fuster et al. showed TET2-mutant blood cells—common in the elderly—accelerate atherosclerosis via proinflammatory macrophages. Aging bone marrow may fuel cardiovascular aging.

Ning Huang #JournalClub.
www.science.org/doi/10.1126/...

Activation of lysosomal iron triggers ferroptosis in cancer - Nature Some cancer cells exhibit high loads of reactive iron in lysosomes, and this feature is exploited by using fentomycin-1, a newly developed small molecule, to induce ferroptosis.

Tatiana Cañeque et al. (Rodriguez lab) develop Fento-1, a new molecule that eliminates therapy-resistant CD44⁺ cancer stem cells by targeting lysosomal iron and inducing ferroptosis.

Presented by PhD student Francesca Cogo at #JournalClub.

www.nature.com/articles/s41...

Fascinating study from @miriammerad.bsky.social ’s lab suggests our aging immune system may drive cancer. With age, bone marrow–derived monocyte-lineage cells replace resident lung myeloid cells — fueling tumor growth via IL-1 secretion.

👉https://www.science.org/doi/10.1126/science.adn0327

Cell cycle duration determines oncogenic transformation capacity - Nature Total cell cycle duration is a key hallmark of cancer initiation, and determines whether defects in apoptosis, senescence, immune surveillance, angiogenesis, DNA repair, polarity and proliferation lea...

Francesca Cogo (PhD student) at #JournalClub:

Danian Chen et al. show that shorter cell cycle duration increases susceptibility to tumor initiation—making it a key hallmark of cancer initiation.

www.nature.com/articles/s41...

Imagine a world where you can choose your child’s traits or rewrite your own genes to cure disease or extend life. This month, we recommend The Gene by Siddhartha Mukherjee — a gripping history of how we came to understand, and are beginning to rewrite, the code of inheritance.

Increased iron uptake by splenic hematopoietic stem cells promotes TET2-dependent erythroid regeneration - Nature Communications The cues guiding hematopoietic stem cells (HSCs) to regenerate specific cell types lost due to injury remain elusive. This study shows that iron instructs erythroid differentiation of HSCs during anem...

"Yu-Jung Tseng and colleagues @NakadaLab show that iron acts as a critical signal to activate splenic blood stem cells for red blood cell production during acute anemia — in a TET2-dependent manner." - Ning Huang, PhD student

#JournalClub

www.nature.com/articles/s41...

🚀 Recently, we welcomed Sefora Conti as our #JournalClub invited speaker! She shared how she has used tools from mechanobiology, meta-analysis, and bioinformatics to uncover what drives metastasis in gastrointestinal tumors.

👉https://vhio.net/pf/upper-gastrointestinal-and-endocrine-tumor-group/

Epigenetic and proteomic signatures associate with clonal hematopoiesis expansion rate - Nature Aging Exploring the clonal expansion of somatically mutated hematopoietic stem cells with aging, Mack, Raddatz et al. quantify rates of clonal expansion in 4,370 individuals in the Trans-Omics for Precision...

#JournalClub

"We’re born as genomic mosaics, each cell unique. With age, this diversity is overtaken by a few dominant clones — a shift linked to frailty. Mack et al. dive into large human datasets to uncover what drives this process." - Mate Maus

www.nature.com/articles/s43...

#JournalClub

"Ian Folkert and and colleagues show that iron-rich tumor-associated macrophages shape anti-tumor immunity — pointing to a promising new target to boost immunotherapy responses." - Marc Guasch, PhD student

rupress.org/jem/article/...

Potentiation of Doxorubicin Cardiotoxicity by Iron Loading in a Rodent Model The role of iron toward doxorubicin (DOX) cardiotoxicity was studied using a rodent model of dietary carbonyl iron loading.Doxorubicin, a commonly use…

#JournalClub

"Panjrath et al. show that dietary iron loading exacerbates doxorubicin-induced heart damage in rats, highlighting the role of iron in cardiotoxicity." - Francesca Cogo, PhD student

www.sciencedirect.com/science/arti...

Age-, sex- and proximal–distal-resolved multi-omics identifies regulators of intestinal aging in non-human primates - Nature Aging Using a multi-omics approach, Wang et al. explored sex-specific and region-specific patterns of intestinal aging in non-human primates, identifying regulators with conserved functions in Caenorhabditi...

#JournalClub

"Wang et. al identify mechanisms underlying intestinal aging in non-human primates with a multi-omics approach, and assess their functional relevance in C. elegans models." - Marc Guasch, PhD student

www.nature.com/articles/s43...

Inhibition of IL-11 signalling extends mammalian healthspan and lifespan - Nature IL-11 is identified as a key regulator of ERK–AMPK–mTORC1 signalling, metabolism, inflammation and age-related disease and lifespan in mouse and human.

#JournalClub

"In search of lifespan-extending interventions, Widjaja et al. show that inhibiting IL-11—a pro-inflammatory protein—improves late-life health and extends lifespan in mice. Whether this translates to humans remains to be seen." – Mate Maus

www.nature.com/articles/s41...

Doxorubicin causes ferroptosis and cardiotoxicity by intercalating into mitochondrial DNA and disrupting Alas1-dependent heme synthesis Restoration of heme synthesis alleviates anthracycline-induced ferroptosis and cardiotoxicity.

#JournalClub

"Abe et al. show that doxorubicin induces heart damage by disrupting heme synthesis and cellular iron metabolism, and highlight 5-ALA as a potential therapeutic for cancer survivors" - Francesca Cogo, PhD student

www.science.org/doi/10.1126/...

Iron trapping in macrophages reshapes the homeostasis of the haematopoietic system Deletion of ferroportin (Fpn) in myeloid cells results in iron trapping in macrophages and reshapes whole haematopoiesis with ageing. Impaired local iron supply to bone marrow (BM) leads to anaemia a...

#JournalClub

"Laura Crisafulli and her colleagues found that mouse models with iron trapping in macrophages develop microcytic anemia, with interesting implications for aging." - Ning Huang, PhD student

onlinelibrary.wiley.com/doi/10.1111/...

🚨 3 days left! 🚨

2 POSTDOC positions
The metabolically aged microenvironment in immune evasion and cancer

Aging and Cancer Lab, VHIO, Barcelona

Learn more at: mauslab.org/join-us