A5047328359- Telomeres, Telomerase, and Senescence
- Amyotrophic Lateral Sclerosis Research
- Chromosomal and Genetic Variations
- Genetics, Aging, and Longevity in Model Organisms
- Neurogenetic and Muscular Disorders Research
- Muscle Physiology and Disorders
- Polyamine Metabolism and Applications
- Plant Molecular Biology Research
- CRISPR and Genetic Engineering
- Genetic Neurodegenerative Diseases
- biodegradable polymer synthesis and properties
- Adipose Tissue and Metabolism
- Genomics and Chromatin Dynamics
- FOXO transcription factor regulation
- Epigenetics and DNA Methylation
- Cannabis and Cannabinoid Research
- Aquaculture disease management and microbiota
- Invertebrate Immune Response Mechanisms
- Synthetic Organic Chemistry Methods
- Science, Research, and Medicine
- Single-cell and spatial transcriptomics
- Neurobiology and Insect Physiology Research
- Ubiquitin and proteasome pathways
- Children's Physical and Motor Development
- Inflammasome and immune disorders
Sapienza University of Rome
2015-2025
Institute of Molecular Biology and Pathology
2020-2025
Instituto Gulbenkian de Ciência
2019-2024
University of Minnesota
2018
Istituto Pasteur
2015
European University of Rome
2015
Summary Stress and low socioeconomic status in humans confer increased vulnerability to morbidity mortality. However, this association is not mechanistically understood nor has its causation been explored animal models thus far. Recently, cellular senescence suggested as a potential mechanism linking lifelong stress age‐related diseases shorter life expectancy humans. Here, we established causal role for social on shortening lifespan increasing the risk of cardiovascular disease mice....
Significance Cancer incidence increases exponentially in human midlife. Even though mutation accumulation somatic tissues results increased tumorigenesis, it is currently not understood how aging contributes to cancer. Telomeres, the ends of eukaryotic linear chromosomes, shorten with each cell division. Here, we show that telomere shortening cancer a noncell autonomous manner. Using embryo chimeras telomerase-deficient zebrafish generated from melanoma-prone fish, tumors arise more...
Progressive telomere shortening during lifespan is associated with restriction of cell proliferation, genome instability and aging. Apoptosis senescence are the two major outcomes upon irreversible cellular damage. Here, we show a transition these fates aging telomerase deficient zebrafish. In young mutants, proliferative tissues exhibit DNA damage p53-dependent apoptosis, but no senescence. However, in older animals display loss cellularity becomes predominant. Tissue alterations...
Abstract Background The ribonuclear protein TDP-43 has been implicated in the pathophysiology of amyotrophic lateral sclerosis (ALS), with genetic mutations being linked to neurological symptoms disease. Though alterations intracellular distribution have observed skeletal muscles patients suffering from ALS, it is not clear whether such modifications play an active role disease or merely represent expression muscle homeostatic mechanisms. Also, molecular and metabolic pathways regulated by...
Caspase-8 is a cysteine protease historically regarded as anti-neoplastic protein, thanks to its role in apoptosis. However, expression retained or even enhanced several tumors, including glioblastoma (GBM), where it plays pro-tumor functions. We previously reported that negative prognostic factor and contributes resistance against DNA damaging agents, such ionizing radiations (IR) Temozolomide, commonly used standard GBM treatment. therefore investigated whether may sustain repair pathways...
Crosses between Drosophila melanogaster females and simulans males produce hybrid sons that die at the larval stage. This lethality is suppressed by loss-of-function mutations in D. Hybrid male rescue (Hmr) or Lethal (Lhr) genes. Previous studies have shown Hmr Lhr interact with heterochromatin proteins suppress expression of transposable elements within It also has been proposed function centromere. We examined mitotic divisions brains from single mutants Hmr; double In none did we observe...
Drosophila telomeres are sequence-independent structures that maintained by transposition to chromosome ends of three specialized retroelements (HeT-A, TART and TAHRE; collectively designated as HTT) rather than telomerase activity. Fly protected the terminin complex (HOAP-HipHop-Moi-Ver) localizes functions exclusively at non-terminin proteins do not serve telomere-specific functions. Although all terminate with HTT arrays capped terminin, they differ in type subtelomeric chromatin; Y, XR,...
Microsatellite expansions of CCTG repeats in the cellular nucleic acid-binding protein (CNBP) gene leads to accumulation toxic RNA and have been associated with myotonic dystrophy type 2 (DM2). However, it is still unclear whether dystrophic phenotype also linked CNBP decrease, a conserved CCHC-type zinc finger RNA-binding that regulates translation required for mammalian development. Here, we show depletion Drosophila muscles causes ageing-dependent locomotor defects are correlated impaired...
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, represents a well-recognized biomarker used to assess senescence both vivo and cell culture. The use chromogenic substrate, such as 5-bromo-4-chloro-3-indoyl-β-d-galactopyranoside (X-Gal), allows detection SA-β-GAL activity at pH 6.0 by release visible blue product. Senescence occurs during aging part process itself. We have...
Aging progressively modifies the physiological balance of organism increasing susceptibility to both genetic and sporadic neurodegenerative diseases. These changes include epigenetic chromatin remodeling events that may modify transcription levels disease-causing genes affecting neuronal survival. However, how these interconnect is not well understood. Here, we found Su(var)3-9 causes increased methylation histone H3K9 in promoter region TDP-43, most frequently altered factor amyotrophic...
Abstract Aging progressively modifies the physiological balance of organism increasing susceptibility to both genetic and sporadic neurodegenerative diseases. These changes include epigenetic chromatin remodeling events that may modify gene transcription. However, how aging interconnects with disease-causing genes is not well known. Here, we found Su(var)3-9 causes increased methylation histone H3K9 in promoter region TDP-43, most frequently altered factor amyotrophic lateral sclerosis...
Abstract Telomere shortening occurs in multiple tissues throughout aging. When telomeres become critically short, they trigger DNA damage responses and p53 stabilization, leading to apoptosis or replicative senescence. In vitro , cells with short activate the cGAS-STING innate immune pathway resulting type I interferon inflammation However, consequences of these events organism are not yet understood. Here, we show that sting is responsible for premature aging telomerase-deficient zebrafish....
Abstract Cell types can be now defined at unprecedented resolution using high throughput assays. We analyzed the transcriptional signatures of Drosophila neurons, glia and hemocytes, as examples cell that are related by position (glia/neurons) or function (glia/hemocytes) unrelated (neurons/hemocytes). The most cells display highest similarity level (neurons glia), least ones, lowest hemocytes), however, show plastic features. Glia much more similar to neurons than hemocytes in embryo, but...
Drosophila telomeres are maintained by transposition to chromosome ends of the HeT-A, TART and TAHRE retrotransposons, collectively designated as HTT. Although all terminate with HTT arrays capped terminin complex, they differ in type subtelomeric chromatin. The sequences YS, YL, XR, 4L juxtaposed constitutive heterochromatin, while HTTs other linked either TAS repeat-associated chromatin (XL, 2L, 2R, 3L, 3R) or specialized 4R We found that mutations pendolino (peo) cause (telomeric fusions)...
Abstract Crosses between Drosophila melanogaster females and simulans males produce hybrid sons that die at the larval stage. This lethality is suppressed by loss-of-function mutations in D. Hybrid male rescue ( Hmr ) or Lethal Lhr) genes. Previous studies have shown Lhr interact with heterochromatin proteins suppress expression of transposable elements within . It also has been proposed function centromere. We examined mitotic divisions brains from single mutants Hmr; double In none did we...
ABSTRACT Microsatellite expansions of CCTG repeats in the CNBP gene leads to accumulation toxic RNA and have been associated DM2. However, it is still unclear whether dystrophic phenotype also linked decrease, a conserved CCHC-type zinc finger binding protein that regulates translation required for mammalian development. Here we show depletion Drosophila muscles causes age-dependent locomotor defects are correlated with impaired polyamine metabolism. We demonstrate levels ornithine...
Abstract Cancer incidence increases exponentially with age, when human telomeres are shorter. Similarly, telomerase mutant zebrafish ( tert ) have premature short and anticipate cancer to younger ages. However, because constitute a road block cell proliferation, telomere shortening is currently viewed as tumor suppressor mechanism should protect from cancer. This conundrum not fully understood. In our current study, we report that promotes in non-cell autonomous manner. Using chimeras, show...
This paper report presents the interdisciplinary science showcased at Young Scientists Retreat 2019. The retreat was jointly organized by young researchers from Instituto Gulbenkian de Ciência (Portugal) and Institut Curie (France) took place in Pedrógão Pequeno, a small village central region of Portugal September Three keynote speakers were invited to present their work, Alfonso Martinez-Arias, Biola Javierre Martínez, Sara Magalhães....
ABSTRACT Progressive telomere shortening during lifespan is associated with increased genome instability, block to cell proliferation and aging. Apoptosis senescence are the two main cellular outcomes upon irreversible damage. In this study, we show a transition between apoptosis in cells of independent tissues telomerase zebrafish mutants. young mutants, proliferative exhibit defects p53-dependent apoptosis, but no senescence. Progressively, these display signs tissue dysfunction, loss...