3-7th March 2025
Dive into ageing biology through seminars by top researchers from UniCA, UniGe and USE, and develop hands-on lab skills in ageing research with immersive sessions in specialised labs.
If you wish to attend this event virtually (and you haven’t already registered) you can register here: CLOSED
VENUE
Address: 28 Avenue de Valrose 06103 Nice
Talks taking place in La Salle du Belvédère (Registered participants only). See map below.
Campus Map
AGENDA
Tuesday 25th February – Virtual component
| Time | Seminar |
|---|---|
| 10:00 | Alexandre Ottaviani & Paula Pousinha: Welcome |
| 10:30 | Hannah Walters (Nature Aging Editor): Publishing in Nature Aging Nature Aging is a thematic, multidisciplinary journal publishing high-profile research on all aspects of aging and age-related diseases, as well as reviews, policy and opinion pieces. The journal aims to foster interactions among different areas of the field and to promote new and exciting ideas within and beyond the research community, to enable synergy and maximize scientific and societal impact. This talk will give insights into the editorial process at Nature Aging, from submission to publication, including the initial evaluation of new manuscripts and managing peer review. |
Monday 3rd March – Valrose, Nice
| Time | Seminar |
|---|---|
| 08:30 | Coffee and Registration |
| 09:00 | Bernard Mari (IPMC) : Aging and pulmonary fibrosis: exploration at the single-cell level Lung regeneration is hampered by aging, which increases susceptibility to pathologies such as fibrosis. I will present our recent data presenting a whole picture of cell dynamic changes in lungs from young and aged mice during fibrosis formation and resolution, using notably a combination of single-cell and spatial transcriptomics. We found that transcriptomic alterations in specific cell subpopulations correlated with a delayed fibrosis resolution in aged mice. In particular, several alterations were associated with alveolar mesenchymal cells involved in the homeostasis of the alveolar niche which favors their activation towards myofibroblasts, the effector cells producing a high quantity of extracellular matrix. We also characterized the appearance of pro-angiogenic pulmonary capillary endothelial cells (PCEC) subpopulations associated with the alveolar regeneration process. In aged mice, recruitment of these PCEC subpopulations is delayed, paralleling the retarded resolution of lung fibrosis observed in aged animals. Overall, our data indicate that age-associated transcriptomic alterations in specific mesenchymal and endothelial subpopulations interfere with the lung progenitor differentiation associated with a normal repair process and contribute to the persistent fibrotic process typical of the human pathology. |
| 09:45 | Sabrina Ono (Ulysseus IHM): Discovering the Innovation Hub of Ulysseus in Ageing and Wellbeing |
| 10:30 | Coffee |
| 11:00 | Eirini Trompouki (IRCAN): Lack of MDA5 delays HSC aging partly by retaining proteostasis. Alterations in the hematopoietic system characterized by inflammaging and immunosenescence are among the cornerstones of aging. How age-induced changes are controlled however remains largely unknown. Here, by investigating the role of the innate immune RNA sensor, melanoma differentiation-associated protein 5 (MDA5), we found its important role in hematopoietic stem cell (HSC) aging. Several hallmarks of aging were alleviated in the hematopoietic system of Mda5-/-. Overall, we observed decreased inflammation in aged Mda5-/- HSCs and their bone marrow (BM) microenvironment concurrent with reduced accumulation of aged and myeloid biased Mda5-/- HSCs. These cellular changes were coupled with various alterations in metabolic parameters that pointed to a global delay in aging for Mda5-/-HSCs. Concomitantly aged Mda5-/- HSCs remain more quiescent with better repopulation capacity than WT HSCs. Mechanistically, genome-wide and single cell analysis data indicated that HSF1, the master regulator of proteostasis, is the upstream regulator of the deregulated genes in aged Mda5-/- HSCs. Indeed, aged Mda5-/- HSCs retain better proteostasis while various beneficial aspects of the aging phenotypes could be reversed with the addition of HSF1 inhibitor. In contrast, different aging phenotypes in wild-type cells were rescued with HSF1 activator. Overall, our results show that attenuating Mda5 can delay the effects of aging in the HSC compartment by fine tuning inflammation and retaining active proteostasis. |
| 11:45 | Bjorn Schumacher (CECAD, Germany): Genome stability in Aging and Disease |
| 12:30 | Lunch and Poster Session |
| 13:30 | Transport to Labs |
| 14:00 | Lab Immersion projects |
| 17:00 | Transport back to Valrose |
| 19:00 | Reception Dinner |
Monday 3rd March – EVENING DINNER 19h15
Restaurant Villa d’Este
6 rue massena
0600 Nice
| FIRST NAME | LAST NAME |
| Alberto | RIVERA RAMOS |
| Alexandre | Ottaviani |
| Bibiána | ONDREJOVA |
| Brenda | dias |
| Candela | ARRIBAS PAREJA |
| Clara | GARCIA MAYOR |
| Diego | BAENA LOPEZ |
| Dilara | Diken |
| Djerbi | |
| Elaheh | KHALEDIZADEH |
| Fatemeh | Mohammadipanah |
| Jesus | SOLDAN HIDALGO |
| Joana | FERREIRA |
| João | MARTINS |
| John | Rowell |
| Jose Antonio | ECERRA GALLARDO |
| Katarína | DUDOVA |
| Luca | TAGLIAFICO |
| Luisa | LOPES |
| Manuel | GONZALEZ VAZQUEZ, |
| Manuel | silva |
| Maria | PAREDES SANCHEZ |
| Maria | DEMONTIS |
| Nicolas | CAPELO CARRASCO, |
| Pauline | colibert |
| Petra | Kolembusová |
| Sandro | ARGUELLES CASTILLA |
| Simon | Duchesne |
| Sonia Maria | GULABRAI DIAZ |
| Stefania | PERUZZO |
| Veronika | SEDLAKOVA |
| Viktória | RAJTUKOVA |
Tuesday 4th March – Valrose, Nice
| Time | Seminar |
|---|---|
| 08:30 | Coffee |
| 09:00 | Raphaëlle Pardossi (IPMC): Deciphering early mechanisms of Alzheimer’s disease: A focus on C99 Alzheimer’s disease (AD) is a progressive neurodegenerative disorder responsible for the most common form of dementia. It is characterized by two main histological brain deposits: the intracellular neurofibrillary tangles (NFTs) containing aggregates of Tau protein and the extracellular senile plaques composed of amyloid-b (Ab) peptides. The amyloid hypothesis proposes an important role of Ab in the etiology of AD. However, an increasing number of evidences indicate that Aβ can likely not account for all aspects of the disease and our research demonstrated that C99, the direct precursor of Ab generated upon b-secretase cleavage in the amyloidogenic pathway, could also contribute to the pathology. I will present you our data demonstrating an early brain accumulation of C99 in 3xTgAD mice (1) that is tightly linked to synaptic and cognitive alterations (2, 3). This early accumulation of C99 is also associated with a strong reduction of mouse spontaneous activity measured by actimetry (2, 3), a phenotype reminiscent of an apathy-like phenotype that is the earliest neuropsychological alteration observed in AD patients. We have also reported that C99 triggers an Aβ-independent lysosomal-autophagic dysfunction (4) in 3xTgAD mice as well as in a new mouse model based on C99 viral expression. More recently, we have demonstrated the contribution of C99 on mitochondrial and mitophagy dysfunctions and reported a mitochondrial accumulation of C99 in human post-mortem sporadic AD brains that correlated with mitophagy failure molecular signature (5). Together, these data demonstrate that C99 could be an early etiological trigger to AD pathology. |
| 09:45 | Dmitry Bulvain (IRCAN): Crosstalk Between Senescence and Disease Tolerance as a Broad Defense and Health-Span Extending Strategy Traditionally, an organism’s ability to overcome infectious diseases has been linked to the elimination of invading pathogens. However, accumulating evidence suggests that, in addition to restricting pathogen loads, survival is also influenced by a less understood mechanism known as disease tolerance. In this context, I will present the crosstalk between senescence and disease tolerance and discuss how this knowledge could serve as a potential entry point for improving health- and lifespan. |
| 10:30 | Coffee |
| 11:00 | Joana Ferreira (MIA, Portugal): Advanced Fluorescent Microscopy Techniques for Ageing Biology: Challenges and Future Perspectives Fluorescent microscopy has revolutionized our ability to visualize and analyze cellular processes, offering unprecedented insights into the mechanisms of ageing. This lecture will explore cutting-edge fluorescence-based imaging techniques, including super-resolution microscopy, fluorescence lifetime imaging (FLIM), and Förster resonance energy transfer (FRET), and their applications in ageing biology. We will discuss current challenges, such as phototoxicity, resolution limits, and quantitative imaging constraints, as well as emerging innovations that promise to overcome these hurdles. Finally, we will look ahead to future perspectives in the field, discussing AI-driven image analysis and novel fluorophores, which hold the potential to transform our understanding of cellular ageing. This session aims to provide researchers with a comprehensive overview of the latest microscopy advancements and their implications for ageing research. |
| 11:45 | Luisa V Lopes (GIMM, Portugal): Circadian Dysfunction as a Biomarker in Cognitive Aging. Aging is associated with cognitive decline, often attributed to synaptic alterations rather than significant neuronal loss. Emerging research suggests that circadian rhythm disruption plays a critical role in cognitive aging, impacting hippocampal function, synaptic plasticity, and overall brain connectivity. This talk explores the link between circadian dysfunction and cognitive decline, presenting evidence from anatomical tracing, functional brain imaging, and in-vivo electrophysiological recordings. We discuss how disruptions in hippocampal-cortical communication and altered theta oscillations may underlie cognitive impairments in aging. These findings highlight circadian dysfunction as a potential biomarker and target for interventions in age-related cognitive disorders. |
| 12:30 | Lunch and Poster Session |
| 13:30 | Transport to Labs |
| 14:00 | Lab Immersion projects |
| 17:00 | Transport back to Valrose |
Wednesday 5th March – Valrose, Nice
| Time | Seminar |
|---|---|
| 08:30 | Coffee |
| 09:00 | Herve Techer (IRCAN): Cytosolic DNA sensing and interferon signaling in senescence and aging. Cancer, increasingly recognized as an age-associated disease, shares common molecular hallmarks with aging, notably genomic instability and inflammation. DNA replication stress (RS) and chromosomal instability in cancer cells trigger an inflammatory response, mediated by cytosolic DNA (cytoDNA) accumulation and cGAS-STING pathway activation. While acute inflammation can promote tumor rejection, chronic inflammation contributes to aging, cancer development, and auto-inflammatory disorders like the Aicardi-Goutières Syndrome (AGS). TREX1, a crucial cytosolic exonuclease, degrades cytoDNA, and its mutations lead to interferonopathies, notably AGS or familial lupus. TREX1 deficiency results in cytoDNA accumulation, sustained type-I interferon response (IFN-I), and DNA damage. Furthermore, TREX1 inactivation promotes senescence (Técher et al. Nat Com 2024). Our recent findings underscore a feedback loop mechanism linking RS-induced inflammation to genomic instability in senescence. This highlights the intricate interplay between inflammatory signaling, chromosomal integrity, and senescence. Taken together, these recent advances contribute to our understanding of aging and age-related diseases. |
| 09:45 | Sandro Argüelles (Univeristy of Seville): Translational Reprogramming and Immune Response During Cellular Senescence. This seminar will explore the relationship between translational reprogramming and the immune response during cellular senescence and aging. It will discuss how changes in general protein synthesis and Internal Ribosome Entry Sites (IRE) impact immune responses, particularly in the context of immunotherapy. General protein synthesis is typically cap-dependent, but during stress or specific conditions, cells can switch to cap-independent translation mechanisms, such as IREs. IRE-mediated translation can selectively enhance the production of proteins involved in stress responses, apoptosis, and immune regulation. The seminar will also highlight the potential significance of the translation elongation factor 2 (eEF2) in these processes. Understanding these dynamics can help in designing better immunotherapeutic strategies. |
| 10:30 | Coffee |
| 11:00 | John Rowell (UniCA): Breaking Silos: Building Collaborative Bridges in Aging Research. Aging is a multifaceted process that spans molecular biology, clinical research, computational modeling, and social sciences. Yet, research efforts often remain siloed within specific disciplines and institutions, limiting our ability to address aging holistically. In this talk, we will explore the challenges of interdisciplinary collaboration and the necessity of bridging gaps between research domains. Using the creation of a Fédération de Recherche on Aging Biology as a case study, we will discuss strategies for fostering synergy across laboratories, universities, and disciplines. By identifying common goals and shared resources, we can create a more integrated and impactful approach to aging research. The session will conclude with an interactive activity, inviting participants to envision their role in this collaborative future. |
| 11:45 | Simon Duchesne (University Laval): A computational model of brain health, with implications for neurodegeneration. We propose a foray into brain health, cognitive decline, and Alzheimer’s disease (AD), emphasizing the multifactorial nature of these issues. Our central thesis is that brain health must be viewed as a complex system; and we observe that current data mining approaches are limited in their comprehensiveness. Consequently, we propose to use computational models to handle this complexity, built from first principles. We will discuss how the choice of entities, equations, parameters, and initial conditions in these mathematical models is crucial for their accuracy and effectiveness; how pathologies such as Alzheimer’s disease seem to naturally arise in large populations; and how sensitivity analyses can highlight the need for a global and preventive strategy, rather than the current focal and corrective approach. |
| 12:30 | Lunch and Poster Session |
| 13:30 | Transport to Labs |
| 14:00 | Lab Immersion projects |
| 17:00 | Transport back to Valrose |
| 19:00 | Networking event |
Wednesday 5th March – Network event 19h-21h
*Miamici* Trattoria italienne contemporaine à Nice
20 Bd Victor Hugo, 06000 Nice
https://www.mi-amici.com/ Wednesday March 5th 7 PM – 9 PM
PLEASE make sure you have registered here (not needed if you are already a participant of the course) and select that you would like to come to the event: https://forms.gle/b7DuCZxVbTBT9p2M8
Thursday 6th March – Valrose, Nice
| Time | Seminar |
|---|---|
| 08:30 | Coffee |
| 09:00 | Miguel Godinho Ferreira (IRCAN): Organ communication in aging of zebrafish. Telomere shortening is a hallmark of aging, counteracted by telomerase. In zebrafish, the intestine is among the first organs to show signs of aging, such as short telomeres and functional decline. This is particularly pronounced in telomerase mutant zebrafish (tert-/-). Our study reveals that inducing telomerase expression in enterocytes in the gut of tert mutants prevents premature aging. This intervention not only reverses intestinal senescence, apoptosis, and inflammation but also restores gut barrier functions and microbiota dysbiosis to young WT zebrafish. Remarkably, this gut-specific enhancement also improves conditions in remote organs like the testis and kidney marrow, restores fertility, and extends lifespan. These findings highlight the gut’s central role in systemic aging, suggesting that maintaining telomere length there can broadly counteract the aging process in zebrafish. |
| 09:45 | Stephen Ramanoel (LAMHESS): Where is my Body? Respective Contribution of Cognitive and Motor Aging on Spatial Navigation Abilities. Aging is associated with a complex array of structural and functional changes, that gradually affect motor, sensory, and cognitive processes. In this context, spatial navigation offers a representative case of intricate high-level functions that involve dynamic interactions of multi-sensory perceptual, cognitive, and motor processes. The age-related decline in spatial performances has mainly been ascribed to dysexecutive functions and memory deficits. In contrast, the impact of age-related motor impairments on navigational abilities is usually overlooked. To address this gap, we propose to employ the innovative Mobile Brain/Body Imaging approach combining high-density mobile electroencephalography recordings, virtual reality, and motion capture systems to provide unique insights into the behavioral and neural mechanisms underlying age-related spatial abilities deficits under natural conditions. |
| 10:30 | Coffee |
| 11:30 | Lino Ferreira (CNC, Portugal): Cardiovascular aging: modelling and interventions. |
| 12:30 | Lunch |
| 13:30 | Leon Peshkin (Harvard Med School): Systems Biology with AI co-pilots: the hype, the craft and the roadmap. The widely anticipated revolution in biology, driven by the superpowers of GAI, has been slow to materialize. In this talk, we will discuss the concept, the obstacles, and examine two specific projects involving language and image analysis. The first case study involves extracting information from a specific type of biological literature—lifespan extension under pharmacological perturbation—where we aim to agglomerate experimental parameters over extensive body of published literature and automatically review and assess the quality of emerging studies in that context. The second project focuses on image analysis using a novel imaging technique, Stimulated Raman Microscopy, to characterize protein and lipid remodeling in various organs and tissues, to detect changes in a nested hierarchy of repetitive elements of tissue architectures and elucidate changes reflecting sex specificity, aging, and disease. We will anticipate what will be needed for a productive man-machine symbiosis to emerge in systems biology. |
| 14:30 | Group work – preparation of Lab Immersion presentations |
Friday 7th March – Valrose, Nice
| Time | Seminar |
|---|---|
| 08:30 | Coffee |
| 09:00 | Emilio Di Maria (Univeristy of Genoa): A multidisciplinary approach to investigate the genetic determinants of cognitive well-being in the oldest population. Educational attainments, socioeconomic status and mentally stimulating activities, significantly affect late-life cognitive phenotypes. However, as compared to the body of literature on risk factors for dementia, little is known on protective genetic factors associated with a favourable cognitive profile in the oldest population. Across the European countries, Italy and France have a leading position with a swelling population of centenarians. In the Italian map of longevity, Liguria region has the highest ratio incidence of over centenarians. The ongoing study named COOL (Centenarians and oldest-olds in Liguria – COOL: investigation on cognitive status in centenarians from Genova) is aimed at identifying genomic biomarkers of healthy ageing in centenarians, with specific focus on cognitive status. We designed a not-for-profit, multicentric cohort study involving a series of centenarians (aged >99) living in the Genova area. The relevant phenotype (primary endpoint) is cognitive status; genomic biomarkers will be retrospectively investigated as predictors. Cognitive functions are deeply explored by the mean of a set of neuropsychological tests. The diverse profiles of genomic variants in the study cohort will eventually allow to test different multivariate models to interpret the distribution of cognitive performance among centenarians. The work plan implies a close collaboration between skills: the family doctors are pivotal in the process of information and enrolment of participants; chief medical officers supervise the enrolment and data collection processes, which is carried out by all the investigators; clinical neurologists and neuropsychologists contribute with their expertise for the assessment of cognitive profile; clinical pharmacologists are in charge for the analysis of drug prescription and intake; the clinical geneticists (included the PI) examine the family history data and design the investigation of genomic biomarkers. The multidimensional data set on the cohort of centenarians will constitute a scientific standpoint to explore novel research questions. We will discuss the role for medical genetics in the current epidemiological transition, and how genotype data and phenotype data can be integrated to improve the knowledge on healthy ageing. |
| 09:45 | Florence Besse (iBV): Condensation of translationally-repressed mRNAs in the aging brain. In the healthy nervous system, collections of dynamic condensates enriched in RNA and associated regulatory proteins have been identified. In late onset neurodegenerative diseases, in contrast, accumulation of RNA-protein aggregates with aberrant composition has been reported and linked to disease progression. To explore if and how physiological aging impacts on neuronal RNA- condensates independently of disease context, we study in vivo condensation in the aging Drosophila brain. Our work has uncovered a progressive 3’UTR-dependent recruitment of selected mRNA species into large yet dynamic condensates that repress mRNA translation. Such a recruitment depends on the activity of the PKA kinase. These results highlight the importance of post-transcriptional regulation in aging biology and suggest that co-condensation of selected mRNAs and translation regulators into repressive condensates contribute to the specific post-transcriptional changes in gene expression observed in the course of aging. |
| 10:30 | Coffee |
| 11:00 | Eric Gilson (IRCAN): TRF2, from basic functions to anti-ageing intervention. Telomeres are considered valuable ta rgets to counteract the pathological outcome of aging. To date, most approaches have focused on telomerase. However, telomerase-based therapies revealed limitations and the development of strategies targeting other telomeric factors represents an interesting alternative that needs to be developed. Additionally to the telomerase, telomere function relies on a protein complex, named shelterin that protects natural chromosomal DNA termini from unwanted degradation and instability. Besides its canonical functions at telomeres, recent studies from my team provide evidence that the shelterin subunit TRF2 is naturally downregulated during lifetime in various cell types, a decrease that is not found for the other shelterin subunit, suggesting a specific role of TRF2 in aging. Indeed, I will present evidence that this decreased level has pro-aging effects in zebrafish and mice. I will also provide proof of principle that the anti-aging effects of TRF2 can be modulated pharmacologically by increasing the level of TRF2. |
| 11:45 | Claudia Cavadas (CNC, Portugal): Targeting Neuroendocrine Mechanisms to Delay Aging. In this conference I will share our previous and very recent research where we investigated strategies to delay aging & aging-related disease and dysfunctions, inspired in the hypothalamic functions and in the communication between the periphery and the brain. We showed that caloric restriction induces autophagy in hypothalamic and cortical neurons, and these effects are mediated, in part, by NPY and ghrelin receptors activation [1,2]. In addition, evidence from both hypothalamic neuronal in vitro models and mice overexpressing NPY in the hypothalamus, show that NPY, per se, stimulates autophagy in the hypothalamus [1]. Since both autophagy and NPY levels decrease with age, the rescue of hypothalamic NPY levels provides a new putative strategy to delay aging. In fact, using a premature aging mouse model, the reestablishment of NPY levels specifically in the hypothalamus rescued relevant aging markers, including memory dysfunction. Ans using ghrelin administration we could see a rescue of molecular and histopathological aging features and lifespan extension of a short-lived Hutchinson-Gilford Progeria Syndrome mouse model [3]. In another line of research where we are investigating a fatal genetic neurodegenerative disorder Machado-Joseph (MJD) disorder – that caloric restriction, sirtuin 1 overexpression, or NPY were able to mitigate the motor and balance impairments and cerebellar pathology in a mouse model of MJD [4,5,6]. We are now investigating new diet- or circadian-based interventions to tackle this fatal disease. And more recently, we hypothesized that senescent cells in the skin can spread aging to distant organs, thereby accelerating systemic aging processes, including brain aging [7,8]. We transplanted senescent skin cells (fibroblasts) into the dermis of young mice and assessed various age-associated parameters. The results show that the presence of senescent cells in the dermal layer of young mice increased frailty, and impaired musculoskeletal function. Additionally, there was a significant decline in cognitive function, concomitant with increased expression of senescence-associated markers within the hippocampus brain area. These results support the concept that accumulation of senescent cells in the skin can exert remote effects on other organs including the brain contributing to physical and cognitive decline associated with aging [8]. Our research underscores a relevant role of neuroendocrine mechanisms, particularly hypothalamic function and brain-periphery communication, in regulating aging and age-related diseases. |
| 12:30 | Lunch and Poster Session |
| 14:00 | 15 minute presentations on what students learnt in their lab immersions (group activity) |
| 17:00 | Thank you and goodbye! |
Lab Immersion Placements
If you have any problems, please mail me: John.rowell@univ-cotedazur.fr
| FIRST NAME | LAST NAME | Lab Choice |
| Jose Antonio | ECERRA GALLARDO | Bernard Mari (IPMC) |
| Bibiána | ONDREJOVA | Bernard Mari (IPMC) |
| Katarína | DUDOVA | Eric Rottinger LAB – Discovering non conventionnal innovative model for regeneration and longevity studies |
| Veronika | SEDLAKOVA | Eric Rottinger LAB – Discovering non conventionnal innovative model for regeneration and longevity studies |
| Viktória | RAJTUKOVA | Eric Rottinger LAB – Discovering non conventionnal innovative model for regeneration and longevity studies |
| Elaheh | KHALEDIZADEH | Julien Cherfils-Vicini LAB – NK cell functionality, flows cytmotry , cellular senescence models |
| Manuel | GONZALEZ VAZQUEZ, | Julien Cherfils-Vicini LAB – NK cell functionality, flows cytmotry , cellular senescence models |
| Maria | PAREDES SANCHEZ | Julien Cherfils-Vicini LAB – NK cell functionality, flows cytmotry , cellular senescence models, Gael |
| Luca | TAGLIAFICO | Miguel Godinho Ferreira LAB – Premature aging model in zebrafish larvae with extremely short telomeres. Use of anti-aging drugs to look for rescue effects of a bunch of different phenotypes. |
| Maria | DEMONTIS | Miguel Godinho Ferreira LAB – Premature aging model in zebrafish larvae with extremely short telomeres. Use of anti-aging drugs to look for rescue effects of a bunch of different phenotypes. |
| Stefania | PERUZZO | Miguel Godinho Ferreira LAB – Premature aging model in zebrafish larvae with extremely short telomeres. Use of anti-aging drugs to look for rescue effects of a bunch of different phenotypes. |
| Candela | ARRIBAS PAREJA | Paula Pousinha LAB – Electrophysiological signature of aged neurons |
| João | MARTINS | Paula Pousinha LAB – Electrophysiological signature of aged neurons |
| Clara | GARCIA MAYOR | Raphaelle Pardossi-Piquard LAB – Cellular models of Alzheimer’s disease |
| Nicolas | CAPELO CARRASCO, | Raphaelle Pardossi-Piquard LAB – Cellular models of Alzheimer’s disease |
| Alberto | RIVERA RAMOS | Sonia Dagnino LAB – Characterization of the Exposome for Healthy aging with omics technologies |
| Jesus | SOLDAN HIDALGO | Sonia Dagnino LAB – Characterization of the Exposome for Healthy aging with omics technologies |
| Sonia Maria | GULABRAI DIAZ | Sonia Dagnino LAB – Characterization of the Exposome for Healthy aging with omics technologies |
| Diego | BAENA LOPEZ | Stephen Ramanoel LAB – Experimental paradigms combining immersive virtual reality and mobile electroencephalography to explore the interplay between perception and action in aging |
| Petra | Kolembusová | Stephen Ramanoel LAB – Experimental paradigms combining immersive virtual reality and mobile electroencephalography to explore the interplay between perception and action in aging |
Poster sessions
There will be a small poster session held every lunch time. At the end of the week, participants will vote on the winner of the poster prize. See below when your poster session is.
You can vote on which poster should win a prize here: CLOSED
The winners were:
Poster session allocation
| Session | First Name | Last Name | Poster |
| 03-Mar | Candela | ARRIBAS PAREJA | Title: Replication-Transcription conflicts in Glioblastoma: mechanisms underlying genomic instability and resistance to therapy Abstract: Glioblastoma (GBM) represents the most prevalent and lethal primary brain tumour. Although radiotherapy is the most effective non-surgical GBM therapy, recurrence is universal, in part due to highly tumorigenic Glioblastoma Stem Cells (GSCs, CD133+ cells) population. Targeting GSCs remains a challenging task because of their unique biology and dependency on vital survival pathways, which have equal importance for the maintenance of normal stem cells and progenitors. Given the high degree of genomic instability, and well-defined cellular hierarchies with therapeutically resistance GSCs at the apex, GBM represents an ideal model for identification and pre-clinical evaluation of putatively druggable targets. Our studies showed concurrently high levels of replication stress and global transcription rates in human primary GSCs population, suggesting that Replication-Transcription Conflicts (RTCs) might be increased, triggering a heightened DNA Damage Response leading to the expansion of aggressive GSC clones underpinning the therapeutic resistance. Hence, players involved in solving RTCs will become targets to sensitize GSCs to therapeutic intervention. In this work, we pointed to Homologous Recombination RAD52 protein as one of the key factors in solving RTCs because it is involved in pathways related to Replication-Transcription Conflicts, such as 1) BIR mediating repair and restarting collapsed DNA replication forks, and 2) Transcription-Associated HR Response (TA-HRR) sensing R-loops and repairing precisely transcriptional active regions. Therefore, our hypothesis points to RAD52 as a critical factor for restarting replication forks and promoting the resolution of persistent R-loops in these RTCs, avoiding GSCs apoptosis and promoting therapeutic resistance. After isolating the CD133+ population from patient biopsies, Knock-Out lines for RAD52 will be generated using CRISPR/Cas9, and their DNA Damage Response (DDR) will be characterized. Immunohistochemistry will be performed on TMAs (Tissue Micro-Arrays) derived from glioblastoma samples to identify prognostic factors, and glioblastoma animal models will be established for the discovery of new compounds with therapeutic activity. |
| 03-Mar | Jesus | SOLDAN HIDALGO | Lack of Gal3 Ameliorates Neuroinflammation in Frontotemporal Dementia Model Progranulin (GRN) insufficiency leads to frontotemporal lobar degeneration (FTLD) with TDP-43 and neuronal ceroid lipofuscinosis. In this study, brains from WT, Gal3KO, PGRNKO, and PGRNKO/Gal3KO mice (18 months old) were analyzed using immunofluorescence and confocal microscopy. Results revealed that in PGRNKO mice, Gal3 was primarily located in the corpus callosum, thalamocortical tract, and thalamus. Additionally, a pronounced microgliosis was observed in those regions. In the thalamus of PGRNKO mice, microglia exhibited a phenotypic shift characterised by increased TREM2 and CLEC7A expression. Furthermore, GPNMB, a microglial marker, was upregulated in the sensorimotor thalamic region in the absence of GRN, and its expression further increased in the absence of Gal3, suggesting a potential anti-inflammatory effect. Cortical levels of pro-inflammatory cytokines like KC/GRO, IL-6 and IL-12p70 are increased in absence of GRN, which are restored in PGRNKO/Gal3KO mice. |
| 03-Mar | Manuel | GONZALEZ VAZQUEZ, | Evaluation of the bioactive potential of a Cistaceae species aqueous extract for age-related skin conditions. Ageing affects skin physiology causing dryness, reduced elasticity and loss of firmness due to intrinsic and extrinsic factors. These changes may be mediated by an increase in oxidative stress and matrix metalloproteinase expression, promoting senescent cells, connective tissue degradation and lipid loss. In this context, advanced age and related comorbidities also increase skin susceptibility to recurrent microbial infections, particularly fungal infections caused by dermatophytes species, which can lead to serious complications, prologued treatments periods and development of microbial resistance. For this reason, innovative therapies are urgently needed to manage these infections while supporting skin health during ageing. In this context, our research aims to investigate the phytochemical and pharmacological properties of a Cistaceae medicinal species (HJ) aqueous extract that is traditionally used for the treatment of different skin ailments in rural areas of south-western Spain. To this end, a phytochemical analysis of the HJ aqueous extract was first carried out using UHPLC-HRMS/MS and different colorimetric phytochemical assays. Subsequently, the in vitro antioxidant activity against free radicals, reactive oxygen species, transition metals and pro-oxidant enzymes was investigated. Furthermore, inhibitory activity on tyrosinase and enzymes involved in the degradation and structuration of the skin extracellular matrix – such as elastase, hyaluronidase and collagenase – was assessed. Finally, the effect of this extract on the NIH/3T3 fibroblasts viability and its antifungal activity against different species of dermatophytes was evaluated. The results of this investigation shows that the HJ aqueous extract is rich in a wide variety of phenolic compounds of great interest for skin health, with a high proportion of total phenolics (43% w/w) and flavonoids (18% w/w), together with the presence of proanthocyanidins (4% w/w) and hydroxycinnamic acids (3% w/w). This phytochemical composition may contribute to its tyrosinase (IC50 65.3 ± 2.23 µg/ml), elastase (IC50 214 ± 8.94 µg/ml) and collagenase (IC50 144.45 ± 4.03 µg/ml) inhibitory activities. HJ aqueous extract also exhibits antioxidant and antifungal activities at non-toxic concentrations for NIH/3T3 fibroblasts (≤ 100 µg/ml). In this sense, it is worth mentioning the antioxidant capacity against DPPH• (IC50 9.65 ± 0.49 µg/ml), ABTS•+ (IC50 4.97 ± 0.47 µg/ml), H2O2 (IC50 9.43 ± 0.44 µg/ml), •NO (IC50 38.82 ± 1.73 µg/ml), xanthine oxidase (IC50 27.6 ± 1.59 µg/ml) and Fe2+ (IC50 10.54 ± 0.35 µg/ml), as well as the antifungal activity against Trichophyton mentagrophytes, T. mentagrophytes var. interdigitale, T. rubrum, Epidermophyton floccosum and Microsporum canis, with minimum inhibitory and lethal concentrations ranging from 50 µg/ml to 100 µg/ml. These findings highlight the bioactive potential of HJ aqueous extract to support skin health during ageing and as a potential treatment for fungal skin infections. This motivates further research into its effects, as well as those of its isolated compounds, on other aspects of skin ageing, including chronic lesions, persistent pro-inflammatory environments, cellular senescence, and the proliferation of non-fungal microorganisms. |
| 03-Mar | Nicolas | CAPELO CARRASCO, | Metabolic modulation through pharmacological HIF1α stabilization reduces Alzheimer’s Disease pathology. Currently, most emerging therapies against Alzheimer’s Disease (AD) aim to block or reduce beta-amyloid and phospho-tau pathology, while only some of them target neuroinflammation. However, none has achieved significant overall success. Given that mitochondrial activation of microglia and astrocytes correlates with neuroinflammation and AD progression, we propose a novel treatment based on metabolic modulation via HIF1α stabilization. The presence of HIF1α in glial cells avoids mitochondrial overactivity, returning them to a surveilling role. In vitro, we stimulated primary microglia using extracellular tau vesicles and oligomeric beta-amyloid. Both treatments triggered a strong inflammatory response. Nevertheless, a 12-hour-preincubation of our microglia with a drug which promotes HIF1α stabilization enhanced the phagocytosis and processing of beta-amyloid, modulated the neuroinflammatory response, and downregulated the AKT-mTOR signaling pathway. Additionally, respiration assays demonstrated a significant shift from oxidative phosphorylation to glycolysis in both pathological and homeostatic conditions. Otherwise, a 12-hour incubation of SH-SY5Y-Tau neuronal cultures, which overproduce tau, reduced tau aggregation, and phosphorylation, suggesting an increased capacity of clearance in these treated neurons. In vivo, 21 days of intraperitoneal administration of the same compound in 18-month-old APP751SL mice improved behavioral parameters, as assessed by the nesting and open field tests. These changes correlated with a reduction in hyperphosphorylated tau and total beta-amyloid, alongside improvements in synaptic VGAT and VGLUT levels, confirmed by western blot. The treatment also reduced the activation of the mTOR pathway, indicating a metabolic rewiring. Furthermore, microglial activation markers (Clec7a, Cd45) and pro-inflammatory cytokine levels (Il-1β) measured by RT-qPCR were reduced, while astrocytic reactivity (Gfap, Vim) decreased as well. Our findings suggest that mitochondria influence glial cell activation, making HIF1α stabilization a promising strategy for AD. However, further studies are required to validate this hypothesis. |
| 04-Mar | Clara | GARCIA MAYOR | Title: Microglial depletion strategies as a promising tool to design potential therapies for Alzheimer’s Disease. Abstract: Neuroinflammation is considered to play a crucial role in Alzheimer’s disease (AD) nowadays, placing glial cells on the front page. Although several evidences point to the decline of microglial defensive functions, the contribution of these cells in AD progression is still unknown. In recent years, microglial depletion approaches in mouse models have provided new insights into the role of these cells in physiological and pathological conditions. In this regard, our group has generated a genetic depletion AD model that allows the targeting of microglia in a cell-type specific and tamoxifen inducible fashion. At the same time, we have performed a pharmacological depletion treatment with identical animal ages and recovery times. In accordance with other reports, we observed that microglial depletion is followed by a rapid and complete repopulation. Our results showed that these emerging microglia are less activated and seem to lose their ability to migrate and surround amyloid plaques. The consequences of this new microglial phenotype on the course of Alzheimer’s disease are not yet known. Although we have not observed any differences in the amyloid load or the number of dystrophic neurites , preliminary behavioural tests and the analysis of synaptic proteins have shown a tendency for improvement in the cognitive decline of these AD mice . Our aim now is to shed some light on our understanding of microglia in a disease context and test whether microglial renewal strategies would be or not, a promising therapeutic strategy for neurodegenerative diseases. |
| 04-Mar | Jose Antonio | ECERRA GALLARDO | Title:Impact of Verbascoside on the Production of Inflammatory Mediators in Human Synovial Fibroblasts Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects joints, promoting inflammation and cartilage degradation. Synovial fibroblasts contribute to RA by producing inflammatory mediators. Verbascoside (VB), a phenolic compound from Olea europaea, has antioxidant and anti-inflammatory properties, but its effects on human synovial fibroblasts remain unclear. Objective: To evaluate the anti-inflammatory effects of VB on IL-1β-stimulated SW982 synovial cells by analyzing inflammatory mediator production and related signaling pathways. Methodology: SW982 cells were treated with IL-1β and VB. Cell viability (SRB assay), pro-inflammatory cytokines (TNF-α, IL-6 via ELISA), and inflammatory enzyme expression (COX-2, mPGES-1, Nrf2/HO-1 via Western blot) were analyzed. Results: VB significantly reduced IL-6, TNF-α, and COX-2 expression, while mPGES-1 and Nrf2/HO-1 pathways remained unchanged. Conclusion: VB shows potential as an anti-inflammatory agent for RA, though further in vivo studies are needed. Authors: Becerra Gallardo José Antonio, Muñoz García Rocío, Paredes Sánchez María, Rosillo Ramírez María de los Ángeles, Sánchez Hidalgo Marina. |
| 04-Mar | Maria | PAREDES SANCHEZ | Freeze-dried beer down-regulates IL-1β-induced inflammation in human synovial fibroblast cell line SW982 María Paredes-Sánchez1,2, Rocío Muñoz-García1,2, Elena Talero2,†, and Marina Sánchez-Hidalgo1,2,†,* 1. Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain. 2. Departamento de Farmacología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain. † These authors contributed equally to this work. ABSTRACT Introduction: Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease with an autoimmune component that affects about 1% of the world’s population. It can occur at any age, although the peak incidence is between the ages of 50 and 60. For this reason, its study is essential to improve the quality of life of these patients. RA is characterized by an inflammation of the synovial membrane (synovitis), which leads to hyperplasia, erosion and destruction of the cartilage and bone of the joints. Synovial fibroblasts (SF) play an essential role in inflammation because they present an altered phenotype, producing numerous inflammatory mediators. Beer has always been associated with negative health effects. However, there is an increasing number of studies suggesting that a moderate consumption may confer healthy properties due to its content in phenolic compounds. To date, no studies have been documented in human SF validating its antirheumatic potential, as well as the molecular mechanisms and signalling pathways involved. Objectives: To investigate the effects of freeze-dried beer on interleukin (IL)-1β-induced production of inflammatory mediators in human SF SW982, as well as the signalling pathways involved. Materials and methods: SF cells were cultured and stimulated with IL-1β in the presence or absence of freeze-dried beer (12.5, 25, 50, 100 μg/mL). Cell viability was determined by a sulforrhodamine B (SRB) assay. The levels of tumor necrosis factor-alpha (TNF-α) and IL-6 were analyzed by ELISA. Moreover, changes in the protein expression of COX-2, pp38, pERK and pSTAT-3 were assessed by Western Blot. Results: Freeze-dried beer treatment significantly reduced IL-6 and TNF-α levels, as well as COX-2 overexpression. It also modulated the activation of MAPK and STAT-3 pathways, preventing their phosphorylation. Conclusion: Freeze-dried beer exerted anti-inflammatory activity by downregulation of proinflammatory cytokines such as IL-6 and TNF-α, COX-2 expression and blocking STAT-3 and MAPK signalling pathways in IL-1β-stimulated SF SW982. This study suggests that freeze-dried beer could be involved in new nutritional strategies or as a valuable nutritional supplement in the treatment and/or prevention of RA. |
| 04-Mar | Sonia Maria | GULABRAI DIAZ | Title: Evaluation of hydroxytyrosol permeability across the blood-brain barrier using a triculture model with human primary cells. Abstract: Introduction: In vitro models that can accurately mimic the blood-brain barrier (BBB) in culture are critical tools for the study of drugs/compounds permeability, although reproducing key BBB properties remains challenging. The aim of the present study was to develop a human-origin BBB model in Transwell systems. Materials and methods: The BBB model was based on the co-culture of human primary astrocytes and pericytes on the basolateral side of the insert, and the culture of human brain microvascular endothelial cells on the apical side. To assess the barrier integrity, trans epithelial electrical resistance (TEER) measurements and immunocytochemical assays were performed. Furthermore, the passage of hydroxytyrosol, a polyphenol found in human plasma after the consumption of olive oil, which is known to cross the BBB, was evaluated. Results and discussion: The obtained BBB model showed TEER values ≥ 150 Ω/cm2 and the immunocytochemical assays confirmed the formation of a whole monolayer of cells in the apical side of the insert. Moreover, it has been shown that hydroxytyrosol is able to cross the BBB and is also metabolized by cells giving rise to sulfated and acetylated derivatives. In conclusion, we have established a functional BBB model consisting of primary human cells that will serve as an in vitro tool to jointly assess the passage through the BBB and the ability of the BBB to metabolize hydroxytyrosol. |
| 04-Mar | Pauline | Colibert | Title : « INCREASE OF INTESTINAL PERMEABILITY ON TELOMERASE MUTANT ZEBRAFISH” Pauline COLIBERT1 and Miguel GODINHO FERREIRA1 1- IRCAN – Institute for Research on Cancer and Aging of Nice, Université Côte d’Azur UMR7284 U1081, 06107 Nice, France As humans age, they undergo changes in gut microbe composition. Telomere shortening, a hallmark of aging, occurs particularly quickly in the gut, which is one of the organs with the most accelerated telomere decline, triggering early tissue dysfunction (Demanelis et al., 2020). Similarly, zebrafish, commonly used in various studies on human disease, also exhibit age-related tissue integrity loss, inflammation, and age-dependent microbiota dysbiosis. Telomerase-deficient (tert -/-) zebrafish have become a reference model for telomere shortening and TBD (Telomere Biology Disorder). We propose that these age-dependent changes in gut microbe composition are caused by telomere shortening. Indeed, telomere shortening in gut leads to inflammation than can explain dysbiosis. Strikingly, tert -/- mutants show an increase in intestinal permeability similar to that observed in old wild-type fish. Furthermore, we published that taurine decrease with age in animals and in zebrafish particularly, the use of taurine decrease the senescence and increase the longevity on G2 larvae (Lopes Bastos et al., 2023). We demonstrate that injection of taurine into the gut rescues gut permeability in tert -/- mutant and in old wild-type zebrafish. Our data suggests that telomere shortening in animals leads to disruption of the intestinal barrier (leaky gut), which may be an important event in the aging process, raising the possibility that this may also occur in humans. Older animals may be unable to maintain intestinal permeability, allowing various bacteria and pathobiote to enter and may become harmful for the internal environment causing an hyperaction of immune system. |
| 05-Mar | Diego | BAENA LOPEZ | The natural substance boldine as a protector against physiological changes associated with aging in the central nervous system and skeletal muscle |
| 05-Mar | João | Martins | GluN2B-contaning NMDARs role in Network Activity, Synapse Maturation, and Interaction with EphA4 Abstract Receptors at synapses like NMDA and AMPA receptors play key roles in synaptic plasticity and in shaping neuronal circuits. Their disruption is linked to neurodegenerative diseases like Alzheimer’s disease (AD). EphA4 plays a vital role in regulating dendritic spines, affecting network activity, and the endocytosis of AMPARs via the synaptic proteosome. Past proteomics studies from the group showed decreased EphA4 levels in mice cortical neurons lacking the GluN2B subunit of NMDARs (GluN2B-/-). We propose that EphA4 forms a signaling complex with NMDARs through GluN2B, significantly contributing to the regulation of spine structure and synaptic activity. Our study tackled three main objectives: characterize spine structure and network activity in GluN2B-/- mice cultures; analyze EphA4 expression and activity within these cultures; and explore the interaction between EphA4 and NMDARs. Multi-electrode array analysis revealed that GluN2B-/- cortical cultures had increased firing rates, bursts, and erratic bursting patterns compared to GluN2B+/+, indicating altered network activity. Spine morphology assays showed that GluN2B-/- neurons had more immature dendritic spines, revealing the preponderant role of GluN2B in spine maturation. EphA4’s expression was reduced in GluN2B-/- neurons, specifically in synapses. Our immunoprecipitation assays also disclose a potential EphA4-GluN2B interaction, possibly impacting spine development and network activity. In AD, there is an aberrant activation of EphA4 and GluN2B-NMDARs, which opens the possibility that this complex may contribute to AD synaptopathy. |
| 05-Mar | Luca | TAGLIAFICO | Inorganic Polyphosphate and Fasting: Interactions Between Neuronal Senescence and Cancer Metabolism |
| 05-Mar | Maria | DEMONTIS | Titolo: Caratterizzazione dell’attività neuroprotettiva di estratti di sansa ottenuti a diverse temperature Abstract: In studi precedenti è stato dimostrato come alcune molecole bioattive estratte dalla sansa di oliva della cultivar Taggiasca, tramite un metodo di estrazione innovativo, avessero la capacità di contrastare il danno cellulare indotto dal calcio in neuroni corticali murini. In particolare, è stato osservato come questo estratto fosse in grado di proteggere i neuroni dalla morte indotta da una over stimolazione del recettore NMDA. Lo scopo principale di questo lavoro è stato quello di caratterizzare ulteriormente questo estratto variando la temperatura di estrazione (37°C e 120°C) e andando a valutare l’attività protettiva cellulare e la capacità di regolare l’omeostasi intracellulare del Ca2+. I risultati ottenuti dimostrano che l’unico estratto in grado ancora di proteggere le cellule (bEnd-5 e neuroni), regolando l’omeostasi del Ca2+ intracellulare, rimane quello ottenuto a 180° C. Inoltre, dati preliminari hanno rivelato come solo l’estratto ottenuto a 180°C protegga i neuroni dagli effetti negativi indotti dal Ca2+, regolando anche l’attività proteolitica della calpaina che in condizioni di alterata omeostasi del Ca2+, tende a degradare in modo aberrante i suoi substrati. Infatti, diversi studi hanno confermato il suo ruolo rilevante nei processi di morte neuronale, agendo in particolare su un’importante proteina citoscheletrica che è l’α-spettrina. L’estratto ottenuto a 180° C è in grado di regolare l’azione della calpaina su questo substrato favorendone una digestione modulata. In conclusione, si può ipotizzare che questo estratto, grazie alle sue proprietà protettive e non tossiche sulle cellule, possa essere utile per futuri studi rivolti allo sviluppo di strategie alternative per il trattamento delle neurodegenerazioni. |
| 05-Mar | Stefania | PERUZZO | The estimation of eGFR in the geriatric patient. Evaluation and comparison of different equations |
| 05-Mar | Alberto | Rivera | Galectin-3 depletion tames pro-tumoural microglia and restrains cancer cells growth: Galectin-3 (Gal-3) is a multifunctional protein that plays a pivotal role in the initiation and progression of various central nervous system diseases, including cancer. Although the involvement of Gal-3 in tumour progression, resistance to treatment and immunosuppression has long been studied in different cancer types, mainly outside the central nervous system, its elevated expression in myeloid and glial cells underscores its profound impact on the brain’s immune response. In this context, microglia and infiltrating macrophages, the predominant non-cancerous cells within the tumour microenvironment, play critical roles in establishing an immunosuppressive milieu in diverse brain tumours. Through the utilisation of primary cell cultures and immortalised microglial cell lines, we have elucidated the central role of Gal-3 in promoting cancer cell migration, invasion, and an immunosuppressive microglial phenotypic activation. Furthermore, employing two distinct in vivo models encompassing primary (glioblastoma) and secondary brain tumours (breast cancer brain metastasis), our histological and transcriptomic analysis show that Gal-3 depletion triggers a robust pro-inflammatory response within the tumour microenvironment, notably based on interferon-related pathways. Interestingly, this response is prominently observed in tumour-associated microglia and macrophages (TAMs), resulting in the suppression of cancer cells growth. |
Networking Event 05/03/25 19h-21h
There will be an open network event on Wednesday 5th March where you can socialise and interact with the Ageing research community in Nice.
*Miamici* Trattoria italienne contemporaine à Nice, 20 Bd Victor Hugo, 06000 Nice
https://www.mi-amici.com/ Wednesday March 5th 7 PM – 9 PM
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If you wish to attend this event virtually (and you haven’t already registered) you can register here: CLOSED
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