Current lab members:

• Miguel Godinho FERREIRA (DR2 CNRS)
• Giulia Allavena (MSCA Post-Doc)
• Andreia Marques (PhD Student)
• Ana Cano (MSc students and IE)

Lab Alumni:

Our main goal is to understand the mechanisms that promote the rise of cancer incidence with age and to understand the role telomeres plays on this phenomenon. We have developed novel vertebrate system to study this question – the zebrafish. Contrary to common mouse models, zebrafish has natural shorter telomeres that decline with age and limit cell proliferation and longevity.
Telomeres protect the ends of chromosomes from inappropriately being recognized as a double strand break and constant DNA erosion. As telomeres shorten throughout life, we lose this protection, leading to cell senescence and, possibly, genome instability.
We are testing an hypothesis that attempts to explain the apparent paradox of cancer arising at this stage of low cell proliferation. Due to telomere shortening, senescent cells accumulate with age. These cells secrete a very distinct set of signaling factors, proteases and other molecules (SASP). SASP promotes both malignant phenotypes in culture and tumor growth and invasiveness in vivo. The “seed-and-soil” theory proposes the importance of the microenvironment for carcinogenesis. With aging, senescent cells with short telomeres may provide the right soil for tumors to arise in a non-cell autonomous manner.

Current Projects

Top Publications

• Telomere Dynamics in Zebrafish Aging and Disease
  18 décembre 2024 par Miguel Godinho Ferreira
  Fish telomere lengths vary significantly across the numerous species, implicating diverse life strategies and environmental adaptations. Zebrafish have telomere dynamics that are comparable to humans and are emerging as a key model in which to unravel the systemic effects of telomere shortening on aging and interorgan communication. Here, we discuss zebrafish telomere biology, focusing on the organismal impact of telomere attrition beyond cellular senescence, with particular emphasis on how…
• Telomere length is an epigenetic trait – Implications for the use of telomerase-deficient organisms to model human disease
  5 mars 2024 par Catarina M Henriques
  Telomere length, unlike most genetic traits, is epigenetic, in the sense that it is not fully coded by the genome. Telomeres vary in length and randomly assort to the progeny leaving some individuals with longer and others with shorter telomeres. Telomerase activity counteracts this by extending telomeres in the germline and during embryogenesis but sizeable variances remain in telomere length. This effect is exacerbated by the absence of fully active telomerase. Telomerase heterozygous animals…
• Lack of telomerase reduces cancer incidence and increases lifespan of zebrafish tp53^M214K mutants
  5 mars 2024 par Naz Şerifoğlu
  Telomerase activity is restricted in humans and telomere attrition occurs in several tissues accompanying natural aging. Critically short telomeres trigger DNA damage responses and activate p53 which leads to apoptosis or replicative senescence. These processes reduce cell proliferation and disrupt tissue homeostasis, thus contributing to systemic aging. Similarly, zebrafish have restricted telomerase expression, and telomeres shorten to critical length during their lifespan….
• Pot1 promotes telomere DNA replication via the Stn1-Ten1 complex in fission yeast
  12 novembre 2023 par Pâmela C Carvalho Borges
  Telomeres are nucleoprotein complexes that protect the chromosome-ends from eliciting DNA repair while ensuring their complete duplication. Pot1 is a subunit of telomere capping complex that binds to the G-rich overhang and inhibits the activation of DNA damage checkpoints. In this study, we explore new functions of fission yeast Pot1 by using a pot1-1 temperature sensitive mutant. We show that pot1 inactivation impairs telomere DNA replication resulting in the accumulation of ssDNA leading to…
• Gut-specific telomerase expression counteracts systemic aging in telomerase-deficient zebrafish
  4 mai 2023 par Mounir El Maï
  Telomere shortening is a hallmark of aging and is counteracted by telomerase. As in humans, the zebrafish gut is one of the organs with the fastest rate of telomere decline, triggering early tissue dysfunction during normal zebrafish aging and in prematurely aged telomerase mutants. However, whether telomere-dependent aging of an individual organ, the gut, causes systemic aging is unknown. Here we show that tissue-specific telomerase expression in the gut can prevent telomere shortening and…
• Whole-mount Senescence-Associated Beta-Galactosidase (SA-β-GAL) Activity Detection Protocol for Adult Zebrafish
  8 août 2022 par Marta Marzullo
  Senescence-associated beta-galactosidase (SA-β-GAL) is an enzyme that accumulates in the lysosomes of senescent cells, where it hydrolyses β-galactosides. With p16, it represents a well-recognized biomarker used to assess senescence both in vivo and in cell culture. The use of a chromogenic substrate, such as 5-bromo-4-chloro-3-indoyl-β-d-galactopyranoside (X-Gal), allows the detection of SA-β-GAL activity at pH 6.0 by the release of a visible blue product. Senescence occurs during aging and is…
• Lifespan and telomere length variation across populations of wild-derived African killifish
  26 novembre 2021 par Martin Reichard
  Telomeres and telomerase prevent the continuous erosion of chromosome-ends caused by lifelong cell division. Shortened telomeres are associated with age-related pathologies. While short telomere length is positively correlated with increased lethality at the individual level, in comparisons across species short telomeres are associated with long (and not short) lifespans. Here, we tested this contradiction between individual and evolutionary patterns in telomere length using African annual…
• Telomere shortening produces an inflammatory environment that increases tumor incidence in zebrafish
  20 juin 2020 par Kirsten Lex
  Cancer incidence increases exponentially with age when human telomeres are shorter. Similarly, telomerase reverse transcriptase (tert) mutant zebrafish have premature short telomeres and anticipate cancer incidence to younger ages. However, because short telomeres constitute a road block to cell proliferation, telomere shortening is currently viewed as a tumor suppressor mechanism and should protect from cancer. This conundrum is not fully understood. In our current study, we report that…
• Opposing p53 and mTOR/AKT promote an in vivo switch from apoptosis to senescence upon telomere shortening in zebrafish
  20 mai 2020 par Mounir El Maï
  Progressive telomere shortening during lifespan is associated with restriction of cell proliferation, genome instability and aging. Apoptosis and senescence are the two major outcomes upon irreversible cellular damage. Here, we show a transition of these two cell fates during aging of telomerase deficient zebrafish. In young telomerase mutants, proliferative tissues exhibit DNA damage and p53-dependent apoptosis, but no senescence. However, these tissues in older animals display loss of…
• Ssu72 phosphatase is a conserved telomere replication terminator
  24 février 2019 par Jose Miguel Escandell
  Telomeres, the protective ends of eukaryotic chromosomes, are replicated through concerted actions of conventional DNA polymerases and elongated by telomerase, but the regulation of this process is not fully understood. Telomere replication requires (Ctc1/Cdc13)-Stn1-Ten1, a telomeric ssDNA-binding complex homologous to RPA Here, we show that the evolutionarily conserved phosphatase Ssu72 is responsible for terminating the cycle of telomere replication in fission yeast. Ssu72 controls the…

Lab News

Research Projects

Find out what projects IRCAN researchers are working on at the moment!

Platforms & Services

Find out about our platforms and services that drive our research.

Research Teams

IRCAN has a diverse research teams, tackling a wide range and resolution of topics in ageing and cancer.