122 results on '"Valensin, S."'
Search Results
2. A General Learning Rule for Network Modeling of Neuroimmune Interactome
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Remondini, D., Tieri, P., Valensin, S., Verondini, E., Franceschi, C., Bersani, F., Castellani, G. C., Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Nierstrasz, Oscar, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Sudan, Madhu, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Dough, Series editor, Vardi, Moshe Y., Series editor, Weikum, Gerhard, Series editor, Apolloni, Bruno, editor, Marinaro, Maria, editor, Nicosia, Giuseppe, editor, and Tagliaferri, Roberto, editor
- Published
- 2006
- Full Text
- View/download PDF
3. Memory and Selectivity in Evolving Scale-Free Immune Networks
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Tieri, P., Valensin, S., Franceschi, C., Morandi, C., Castellani, G. C., Goos, Gerhard, editor, Hartmanis, Juris, editor, van Leeuwen, Jan, editor, Timmis, Jon, editor, Bentley, Peter J., editor, and Hart, Emma, editor
- Published
- 2003
- Full Text
- View/download PDF
4. Design, recruitment, logistics, and data management of the GEHA (Genetics of Healthy Ageing) project
- Author
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Skytthe, A., Valensin, S., Jeune, B., Cevenini, E., Balard, F., Beekman, M., Bezrukov, V., Blanche, H., Bolund, L., Broczek, K., Carru, C., Christensen, K., Christiansen, L., Collerton, J.C., Cotichini, R., de Craen, A.J.M., Dato, S., Davies, K., De Benedictis, G., Deiana, L., Flachsbart, F., Gampe, J., Gilbault, C., Gonos, E.S., Haimes, E., Hervonen, A., Hurme, M.A., Janiszewska, D., Jylhä, M., Kirkwood, T.B.L., Kristensen, P., Laiho, P., Leon, A., Marchisio, A., Masciulli, R., Nebel, A., Passarino, G., Pelicci, G., Peltonen, L., Perola, M., Poulain, M., Rea, I.M., Remacle, J., Robine, J.M., Schreiber, S., Scurti, M., Sevini, F., Sikora, E., Skouteri, A., Slagboom, P.E., Spazzafumo, L., Stazi, M.A., Toccaceli, V., Toussaint, O., Törnwall, O., Vaupel, J.W., Voutetakis, K., and Franceschi, C.
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- 2011
- Full Text
- View/download PDF
5. Measuring the genetic influence in modulating the human life span: gene–environment interaction and the sex-specific genetic effect
- Author
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Tan, Qihua, De Benedictis, G., Yashin, A.I., Bonafe, M., DeLuca, M., Valensin, S., Vaupel, J.W., and Franceschi, C.
- Published
- 2001
- Full Text
- View/download PDF
6. Neuroinflammation and the genetics of Alzheimer’s disease: The search for a pro-inflammatory phenotype
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Franceschi, C., Valensin, S., Lescai, F., Olivieri, F., Licastro, F., Grimaldi, L. M. E., Monti, D., De Benedictis, G., and Bonafè, M.
- Published
- 2001
- Full Text
- View/download PDF
7. Do men and women follow different trajectories to reach extreme longevity?
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Franceschi, C., Motta, L., Valensin, S., Rapisarda, R., Franzone, A., Berardelli, M., Motta, M., Monti, D., Bonafè, M., Ferrucci, L., Deiana, L., Pes, G. M., Carru, C., Desole, M. S., Barbi, C., Sartoni, G., Gemelli, C., Lescai, F., Olivieri, F., Marchegiani, F., Cardelli, M., Cavallone, L., Gueresi, P., Cossarizza, A., Troiano, L., Pini, G., Sansoni, P., Passeri, G., Lisa, R., Spazzafumo, L., Amadio, L., Giunta, S., Stecconi, R., Morresi, R., Viticchi, C., Mattace, R., De Benedictis, G., Baggio, G., and the Italian Multicenter Study on Centenarians (IMUSCE)
- Published
- 2000
- Full Text
- View/download PDF
8. Long telomeres and well preserved proliferative vigor in cells from centenarians: A contribution to longevity?
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Franceschi, C., Mondello, C., Bonafè, M., Valensin, S., Sansoni, P., and Sorbi, S.
- Published
- 1999
- Full Text
- View/download PDF
9. Quantifying the relevance of different mediators in the human immune cell network
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Tieri, P., Valensin, S., Latora, V., Castellani, G. C., Marchiori, M., Remondini, D., and Franceschi, C.
- Published
- 2005
10. The network and the remodeling theories of aging: historical background and new perspectives
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Franceschi, C, Valensin, S, Bonafè, M, Paolisso, G, Yashin, A.I, Monti, D, and De Benedictis, G
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- 2000
- Full Text
- View/download PDF
11. Calcium metabolism and vitamin D in the extreme longevity
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Passeri, G, Vescovini, R, Sansoni, P, Galli, C, Franceschi, C, Passeri, M, Italian Multicentric Study on Centenarians 87 Collaborators, Motta, M, Motta, L, Capurso, A, Panza, F, Solfrizzi, V, D'Introno, A, Colacicco, Am, Capurso, S, Capri, M, Salvioli, S, Valensin, S, Bennati, E, Malaguarnera, M, Maugeri, D, Rapisarda, R, Franzone, A, Ferlito, L, De Benedictis, G, Berardelli, M, Masotti, G, Petruzzi, E, Petruzzi, I, Pinzani, P, Monti, D, Antonini, Fm, Capurso, C, Nicita Mauro, V, Lo Balbo, C, Mento, A, Nicita Mauro, C, Maltese, G, Basile, G, Mari, D, Coppola, R, Provenzano, R, Salvioli, G, Baldelli, Mv, Mussi, C, Varricchio, M, Barbieri, M, Gambardella, A, Paolisso, G, Caruso, C, Candore, G, Colonna Romano, G, Lio, D, Biasini, C, Telera, A, Ferrari, E, Cravello, L, Barili, L, Solerte, Sb, Fioravanti, M, Magri, F, Fagnoni, F, Senin, Umberto, Mecocci, Patrizia, Cherubini, Antonio, Marigliano, V, Tafaro, L, Cicconetti, P, Tombesi, F, Tombolillo, Mt, Ettore, E, Forconi, S, Boschi, S, Righi, Ga, Guerrini, M, Giarelli, L, Stanta, G, Ferrucci, L, Ble, A, Metter, Ej, Guralnik, Jm, Pacifici, R, Zuccaro, P, Palmi, I, Branca, S, Fradà, G, Motta, F, Crimi, G., Passeri, G, Vescovini, R, Sansoni, P, Galli, C, Franceschi, C, Passeri, M, Paolisso, G, Barbieri, M, Italian Multicentric Study on Centenarians, (IMUSCE)., Passeri G., Vescovini R., Sansoni P., Galli C., Franceschi C., Passeri M., Italian Multicentric Study on Centenarians (IMUSCE), Motta M., Motta L., Capurso A., Panza F., Solfrizzi V., D'Introno A., Colacicco A.M., Capurso S., Capri M., Salvioli S., Valensin S., Bennati E., Malaguarnera M., Maugeri D., Rapisarda R., Franzone A., Ferlito L., De Benedictis G., Berardelli M., Masotti G., Petruzzi E., Petruzzi I., Pinzani P., Monti D., Antonini F.M., Capurso C., Nicita-Mauro V., Lo Balbo C., Mento A., Nicita-Mauro C., Maltese G., Basile G., Mari D., Coppola R., Provenzano R., Salvioli G., Baldelli M.V., Mussi C., Varricchio M., Barbieri M., Gambardella A., Paolisso G., Caruso C., Candore G., Colonna-Romano G., Lio D., Biasini C., Telera A., Ferrari E., Cravello L., Barili L., Solerte S.B., Fioravanti M., Magri F., Fagnoni F., Senin U., Mecocci P., Cherubini A., Marigliano V., Tafaro L., Cicconetti P., Tombesi F., Tombolillo M.T., Ettore E., Forconi S., Boschi S., Righi G.A., Guerrini M., Giarelli L., Stanta G., Ferrucci L., Ble A., Metter E.J., Guralnik J.M., Pacifici R., Zuccaro P., Palmi I., Branca S., Fradà G., Motta F., Crimi G., Dipartimento di Medicina Interna e Scienze Biomediche, University of Parma = Università degli studi di Parma [Parme, Italie], Dipartimento di Patologia Sperimentale, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Motta, M, Motta, L, Capurso, A, Panza, F, Solfrizzi, V, D'Introno, A, Colacicco, Am, Capurso, S, Capri, M, Salvioli, S, Valensin, S, Bennati, E, Malaguarnera, M, Maugeri, D, Rapisarda, R, Franzone, A, Ferlito, L, De Benedictis, G, Berardelli, M, Masotti, G, Petruzzi, E, Petruzzi, I, Pinzani, P, Monti, D, Antonini, Fm, Capurso, C, Nicita Mauro, V, Lo Balbo, C, Mento, A, Nicita Mauro, C, Maltese, G, Basile, G, Mari, D, Coppola, R, Provenzano, R, Salvioli, G, Baldelli, Mv, Mussi, C, Varricchio, M, Gambardella, A, Caruso, C, Candore, G, Colonna Romano, G, Lio, D, Biasini, C, Telera, A, Ferrari, E, Cravello, L, Barili, L, Solerte, Sb, Fioravanti, M, Magri, F, Fagnoni, F, Senin, U, Mecocci, P, Cherubini, A, Marigliano, V, Tafaro, L, Cicconetti, P, Tombesi, F, Tombolillo, Mt, Ettore, E, Forconi, S, Boschi, S, Righi, Ga, Guerrini, M, Giarelli, L, Stanta, Giorgio, Ferrucci, L, Ble, A, Metter, Ej, Guralnik, Jm, Pacifici, R, Zuccaro, P, Palmi, I, Branca, S, Fradà, G, Motta, F, and Crimi, G.
- Subjects
Male ,Aging ,Bone density ,Osteoporosis ,Parathyroid hormone ,Vitamin D ,Calcium metabolism ,Extreme longevity ,Bone fractures ,Self-sufficiency ,Biochemistry ,Bone remodeling ,0302 clinical medicine ,Endocrinology ,Bone Density ,calcium metabolism, vitamin D, longevity ,ComputingMilieux_MISCELLANEOUS ,Aged, 80 and over ,0303 health sciences ,3. Good health ,Parathyroid Hormone ,030220 oncology & carcinogenesis ,Medicine ,Female ,Risk ,medicine.medical_specialty ,Longevity ,Bone resorption ,vitamin D deficiency ,Article ,03 medical and health sciences ,N-terminal telopeptide ,Internal medicine ,Genetics ,medicine ,Vitamin D and neurology ,Humans ,Bone Resorption ,Molecular Biology ,030304 developmental biology ,business.industry ,Cell Biology ,medicine.disease ,Vitamin D Deficiency ,Diet ,Calcium ,business - Abstract
Skeletal remodelling is a continuous process during life and is still active also in extreme senescence. In the elderly, bone resorption often prevails over bone formation, causing bone loss and fragility. Elderly subjects are exposed to the risk of fractures, and loss of self-sufficiency, if considering that the proximal femur is the most frequently involved site. Bone remodelling can maintain circulating calcium within physiological ranges, at the expense of a substantial loss of this ion from the skeleton, particularly during senescence. Calcium metabolism is regulated at cellular/molecular level by a network of cytokines, growth factors, systemic hormones that act on bone in paracrine/autocrine/systemic fashion. Among the molecules involved in bone metabolism, parathyroid hormone (PTH) and vitamin D present some peculiar aspects during senescence. The osteometabolic features in a consistent group of centenarians have been evaluated. It results that a severe hypovitaminosis D was present in 99 out of 104 centenarians (25-OH vitamin D below 5 nmol/L), and that it plays an important role as a factor inducing a vicious circle involving hypocalcemia, secondary hyperparathyroidism, together with biochemical features indicating a consistent bone loss. Serum C-terminal cross-linking telopeptide, a specific marker of bone resorption was elevated in 92% of these subjects. Moreover, it has been found that several femoral fractures had occurred after 90 years of age. These data offer a rational for the possible prevention of elevated bone turnover, bone loss and consequently the reduction of osteoporotic fractures and fractures-induced disability, in the oldest olds, through the simple supplementation with calcium and vitamin D.
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- 2007
12. Genes and Longevity: Lessons From Studies of Centenarians
- Author
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Yashin, A.I., De Benedictis, G., Vaupel, J.W., Tan, Q., Andreev, K.F., Iachine, I.A., Bonafe, M., Valensin, S., De Luca, M., Carotenuto, L., and Franceschi, C.
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Centenarians -- Genetic aspects ,Longevity -- Genetic aspects ,Health ,Seniors - Abstract
In population studies of aging, the data on genetic markers are often collected for individuals from different age groups. The idea of such studies is to identify 'longevity' or 'frailty' genes by comparing the frequencies of genotypes in the oldest and in the younger groups of individuals. In this paper we discuss a new approach to the analysis of such data. This approach, based on the maximum likelihood method, combines data on genetic markers with survival information obtained from standard demographic life tables. This method allows us to evaluate survival characteristics for individuals carrying respective candidate genes. It can also be used in the estimation of the effects of allele-area and allele-allele interaction, either in the presence or absence of hidden heterogeneity. We apply this method to the analysis of Italian data on genetic markers for five autosomal loci and mitochondrial genomes. Then we discuss basic assumptions used in this analysis and directions of further research.
- Published
- 2000
13. Genome-wide linkage analysis for human longevity: Genetics of Healthy Aging Study
- Author
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Beekman, M., Blanche, H., Perola, M., Hervonen, A., Bezrukov, V., Sikora, E., Flachsbart, F., Christiansen, L., Craen, A.J.M. de, Kirkwood, T.B.L., Rea, I.M., Poulain, M., Robine, J.M., Valensin, S., Stazi, M.A., Passarino, G., Deiana, L., Gonos, E.S., Paternoster, L., Sorensen, T.I.A., Tan, Q.H., Helmer, Q., Akker, E.B. van den, Deelen, J., Martella, F., Cordell, H.J., Ayers, K.L., Vaupel, J.W., Tornwall, O., Johnson, T.E., Schreiber, S., Lathrop, M., Skytthe, A., Westendorp, R.G.J., Christensen, K., Gampe, J., Nebel, A., Houwing-Duistermaat, J.J., Slagboom, P.E., Franceschi, C., GEHA Consortium, Leiden University Medical Center (LUMC), Fondation Jean Dausset - Centre d’Etudes du Polymorphisme Humain [Paris] (CEPH), National Institute for Health and Welfare [Helsinki], Tampere School of Public Health, Institute of Gerontology [Kiev], Nencki Institute of Experimental Biology, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Christian-Albrechts University of Kiel, University of Southern Denmark (SDU), Netherlands Consortium for Healthy Ageing, Newcastle University [Newcastle], The Queen’s University of Belfast, Université Catholique de Louvain = Catholic University of Louvain (UCL), CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société (CERMES3 - UMR 8211 / U988 / UM 7), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-École des hautes études en sciences sociales (EHESS), University of Bologna, Istituto Superiore di Sanita [Rome], Università della Calabria [Arcavacata di Rende] (Unical), Università degli Studi di Sassari = University of Sassari [Sassari] (UNISS), Theoretical and Physical Chemistry Institute NHRF, National Hellenic Research Foundation, University of Bristol [Bristol], Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Odense University Hospital (OUH), Institute for Ageing and Health, Newcastle University, Max Planck Institute for Demographic Research (MPIDR), Max-Planck-Gesellschaft, University of Colorado [Boulder], Leiden University Medical Centre [Leyde, Pays-Bas], Leiden University, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Institute for Ageing and Health, École des hautes études en sciences sociales (EHESS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Sassari, Danish Aging Research Center, Institute of Public Health, and Institute for Behavioral Genetics
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Aging ,Genetic Linkage ,APOE gene ,Genome-wide association study ,Association analysis ,Human familial longevity ,[SHS]Humanities and Social Sciences ,0302 clinical medicine ,Mitochondrial Precursor Protein Import Complex Proteins ,Cluster Analysis ,Nonagenarian sibling pairs ,media_common ,Aged, 80 and over ,Genetics ,0303 health sciences ,Longevity ,Chromosome Mapping ,Middle Aged ,Europe ,genome-wide linkage analysis ,association analysis ,nonagenarian sibling pairs ,apoe gene ,human familial longevity ,congenital, hereditary, and neonatal diseases and abnormalities ,media_common.quotation_subject ,Locus (genetics) ,Biology ,Article ,03 medical and health sciences ,Apolipoproteins E ,SDG 3 - Good Health and Well-being ,Genetic linkage ,Humans ,Allele ,Alleles ,Aged ,030304 developmental biology ,Genetic association ,Chromosomes, Human, Pair 14 ,Apolipoprotein C-I ,Genome, Human ,Siblings ,Membrane Transport Proteins ,Cell Biology ,Heritability ,Apoe gene ,Genetic Loci ,Human genome ,Lod Score ,Chromosomes, Human, Pair 19 ,Genome-wide linkage analysis ,030217 neurology & neurosurgery ,Chromosomes, Human, Pair 17 ,Genome-Wide Association Study - Abstract
Clear evidence exists for heritability of humanlongevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD = 3.47), chromosome 17q12-q22 (LOD = 2.95), chromosome 19p13.3-p13.11 (LOD = 3.76), and chromosome 19q13.11-q13.32 (LOD = 3.57). To fine map these regions linked to longevity, we performed association analysis using GWAS data in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls. Using a fixed-effect meta-analysis approach, rs4420638 at the TOMM40/ APOE/APOC1 gene locus showed significant association with longevity (P-value = 9.6 × 10 -8). By combined modeling of linkage and association, we showed that association of longevity with APOEe4 and APOEe2 alleles explain the linkage at 19q13.11-q13.32 with P-value = 0.02 and P-value = 1.0 × 10 -5, respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12-q22, and 19p13.3-p13.11. As the latter linkage results are not explained by common variants, we suggest that rare variants play an important role in human familial longevity.
- Published
- 2013
14. Genome-wide linkage analysis for longevity in European nonagenarian siblings: Genetics of Healthy Ageing Study (GEHA)
- Author
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Beekman, M., Slagboom, P. E., Blanche, H., Perola, M., Hervonen, A., Bezrukov, V., Sikora, E., Christiansen, L., Schreiber, S., De Craen, A. J. M., Kirkwood, T. B. L., Rea, I. M., Poulain, M., Robine, J. M., Valensin, S., Stazi, M. A., Passarino, G., Deiana, L., Gonos, S., Tornwall, O., Helmer, Q., Martella, Francesca, and Westendorp, R. G. J.
- Published
- 2011
15. Aminopyrimidines as inhibitors of the Wnt signalling pathway
- Author
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DEL BELLO, Fabio, Farande, A., Giannella, Mario, Piergentili, Alessandro, Quaglia, Wilma, Mencini, A., Thomas, R., Varrone, M., Benicchi, T., Benedetti, G., De Robertis, A., and Valensin, S.
- Published
- 2010
16. Defective Vav expression and impaired F-actin reorganization in a subset of common variable immunodeficiency patients with T-cell defects
- Author
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ROSSI PACCANI, Silvia, Boncristiano, M., Patrussi, Laura, Ulivieri, Cristina, Wack, A., Valensin, S., Hirst, T. R., Amedei, A., DEL PRETE, G., Telford, J. L., D'Elios, M. M., and Baldari, Cosima
- Subjects
signal trasduction ,common variable immunodeficiency (CVID) - Published
- 2005
17. F-actin dynamics controls segregation of the TCR signaling cascade to clustered lipid rafts
- Author
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Valensin, S., ROSSI PACCANI, Silvia, Ulivieri, Cristina, Mercati, David, Pacini, S., Patrussi, Laura, Hirst, T., Lupetti, Pietro, and Baldari, Cosima
- Subjects
Tyrosine phosphorylation ,Lipid raft ,Actin cytoskeleton ,Vav ,TCR - Published
- 2002
18. Measuring the genetic influence on human life span: gene-environment interaction and sex-specific genetic effects
- Author
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Tan, Qihua, De Benedictis, G, Yashin, Annatoli, Bonafe, M, DeLuca, M, Valensin, S, Vaupel, J. W., and Franceschi, F
- Subjects
two-step MLE ,longevity ,heterogeneity ,gene ,survival analysis - Abstract
New approaches are needed to explore the different ways in which genes affect the human life span. One needs to assess the genetic effects themselves, as well as gene–environment interactions and sex dependency. In this paper, we present a new model that combines both genotypic and demographicinformation in the estimation of the geneticinfluence on life spans. Based on Cox'sproportional hazard assumption, the modelmeasures the risks for each gene as well as forgene–environment and gene–sex interactions,while controlling for confounding factors. Atwo-step MLE is introduced to obtain anon-parametric form of the baseline hazardfunction. The model is applied to genotypicdata from Italian centenarian studies toestimate relative risks of candidate genes,risks due to interactions and initialfrequencies of different genes in thepopulation. Results from models that either door do not take into consideration individualheterogeneity are compared. It is shown thatignoring the existence of heterogeneity canlead to a systematic underestimation of geneticeffects and effects due to interactions.
- Published
- 2001
19. Defective recruitment and activation of ZAP-70 in CVID patients with T-cell defects
- Author
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Boncristiano, M, Majolini, M. B., D'Elios, M. M., Pacini, S., Valensin, S., Ulivieri, Cristina, Amedei, A., Falini, B., DEL PRETE, G., Telford, J. L., and Baldari, Cosima
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signal trasduction ,ZAP-70 ,protein tyrosine phosphorylation ,common variable immunodeficiency (CVID) ,TCR - Published
- 2000
20. Defective recruitment and activation of ZAP-70 in common variable immunodeficiency patients with T cell defects
- Author
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Boncristiano, M., Majolini, M., D'Elios, M., Pacini, S., Valensin, S., Ulivieri, C., Amedei, A., Falini, Brunangelo, and Et, A.
- Published
- 2000
21. The neuro-immunological interface in an evolutionary perspective: the dynamic relationship between effector and recognition systems
- Author
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Valensin S, Ottaviani E, and Claudio Franceschi
- Subjects
Immunity, Cellular ,Innate immune system ,biology ,Effector ,Neuroimmunomodulation ,Repertoire ,Macrophages ,Perspective (graphical) ,Thymus Gland ,Major histocompatibility complex ,Biological Evolution ,Invertebrates ,Neurosecretory Systems ,Immunity, Innate ,medicine.anatomical_structure ,Immune System ,Vertebrates ,Recognition system ,medicine ,biology.protein ,Macrophage ,Animals ,Neuroscience ,B cell - Abstract
The evolutionary perspective indicates that an immune-neuroendocrine effector system integrating innate immunity, stress and inflammation is present in invertebrates. This defense network, centered on the macrophage and exerting primitive and highly promiscuous recognition units, is very effective, ancestral and appears to have been conserved throughout evolution from invertebrates to higher vertebrates. It would seem that there was a "big bang" in the recognition system of lower vertebrates, and T and B cell repertoires, MHC and antibodies suddenly appeared. We argue that this phenomenon is the counterpart of the increasing complexity of the internal circuitry and recognition units in the effector system. The immediate consequences were a progressive enlargement of the pathogen repertoire and new problems regarding self/not-self discrimination. Probably not by chance, a new organ appeared, capable of purging cells able of excessive self recognition. This organ, the thymus, appears to be the result of a well known evolutionary strategy of re-using pre-existing material (neuroendocrine cells and mediators constituting the thymic microenvironment). This bricolage at an organ level is similar to the effect we have already described at the level of molecules and functions of the defense network, and has a general counterpart at genetic level. Thus, in vertebrates, the conserved immune-neuroendocrine effector system remains of fundamental importance in defense against pathogens, while its efficiency has increased through synergy with the new, clonotipical recognition repertoire.
- Published
- 1998
22. Combining genetic and demographic information in population studies of aging and longevity
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Ai, Yashin, James Vaupel, Af, Andereev, Qihua Tan, Ia, Iachine, Carotenuto, L., Benedictis, G., Bonafe, M., Valensin, S., and Franceschi, C.
- Published
- 1998
23. Systems Biology and Longevity: An Emerging Approach to Identify Innovative Anti- Aging Targets and Strategies
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Cevenini, E., primary, Bellavista, E., additional, Tieri, P., additional, Castellani, G., additional, Lescai, F., additional, Francesconi, M., additional, Mishto, M., additional, Santoro, A., additional, Valensin, S., additional, Salvioli, S., additional, Capri, M., additional, Zaikin, A., additional, Monti, D., additional, de Magalhaes, J., additional, and Franceschi, C., additional
- Published
- 2010
- Full Text
- View/download PDF
24. Inflamm-Aging, Cytokines and Aging: State of the Art, New Hypotheses on the Role of Mitochondria and New Perspectives from Systems Biology
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Salvioli, S., primary, Capri, M., additional, Valensin, S., additional, Tieri, P., additional, Monti, D., additional, Ottaviani, E., additional, and Franceschi, C., additional
- Published
- 2006
- Full Text
- View/download PDF
25. Genes, ageing and longevity in humans: Problems, advantages and perspectives
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Salvioli, S., primary, Olivieri, F., additional, Marchegiani, F., additional, Cardelli, M., additional, Santoro, A., additional, Bellavista, E., additional, Mishto, M., additional, Invidia, L., additional, Capri, M., additional, Valensin, S., additional, Sevini, F., additional, Cevenini, E., additional, Celani, L., additional, Lescai, F., additional, Gonos, E., additional, Caruso, C., additional, Paolisso, G., additional, De Benedictis, G., additional, Monti, D., additional, and Franceschi, C., additional
- Published
- 2006
- Full Text
- View/download PDF
26. Quantifying the relevance of different mediators in the human immune cell network
- Author
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Tieri, P., primary, Valensin, S., additional, Latora, V., additional, Castellani, G. C., additional, Marchiori, M., additional, Remondini, D., additional, and Franceschi, C., additional
- Published
- 2004
- Full Text
- View/download PDF
27. A General Learning Rule for Network Modeling of Neuroimmune Interactome.
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Apolloni, Bruno, Marinaro, Maria, Nicosia, Giuseppe, Tagliaferri, Roberto, Remondini, D., Tieri, P., Valensin, S., Verondini, E., Franceschi, C., Bersani, F., and Castellani, G.C.
- Abstract
We propose a network model in which the communication between its elements (cells, neurons and lymphocytes) can be established in various ways. The system evolution is driven by a set of equations that encodes various degrees of competition between elements. Each element has an "internal plasticity threshold" that, by setting the number of inputs and outputs, determines different network global topologies. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
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28. A Stochastic Model for CD8+T Cell Dynamics in Human Immunosenescence: Implications for Survival and Longevity
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LUCIANI, F., primary, VALENSIN, S., additional, VESCOVINI, R., additional, SANSONI, P., additional, FAGNONI, F., additional, FRANCESCHI, C., additional, BONAFÈ, M., additional, and TURCHETTI, G., additional
- Published
- 2001
- Full Text
- View/download PDF
29. Genes, Demography, and Life Span: The Contribution of Demographic Data in Genetic Studies on Aging and Longevity
- Author
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Yashin, A.I., primary, De Benedictis, G., additional, Vaupel, J.W., additional, Tan, Q., additional, Andreev, K.F., additional, Iachine, I.A., additional, Bonafe, M., additional, DeLuca, M., additional, Valensin, S., additional, Carotenuto, L., additional, and Franceschi, C., additional
- Published
- 1999
- Full Text
- View/download PDF
30. The unexpected contribution of immunosenescence to the leveling off of cancer incidence and mortality in the oldest old
- Author
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Bonafe, M., Valensin, S., Gianni, W., Marigliano, V., and Franceschi, C.
- Published
- 2001
- Full Text
- View/download PDF
31. Immunogenetics of longevity. Is major histocompatibility complex polymorphism relevant to the control of human longevity? A review of literature data
- Author
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Caruso, C., Candore, G., Romano, G. C., Lio, D., Bonafe, M., Valensin, S., and Franceschi, C.
- Published
- 2001
- Full Text
- View/download PDF
32. HLA, aging, and longevity: a critical reappraisal
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Caruso, C., Candore, G., Romano, G. Colonna, Lio, D., Bonafe, M., Valensin, S., and Franceschi, C.
- Published
- 2000
- Full Text
- View/download PDF
33. Biomarkers of immunosenescence within an evolutionary perspective: the challenge of heterogeneity and the role of antigenic load - the Swedish longitudinal OCTO-immune study
- Author
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Franceschi, C., Valensin, S., Fagnoni, F., Barbi, C., and Bonafe, M.
- Published
- 1999
- Full Text
- View/download PDF
34. Genes involved in immune response/inflammation, IGF1/insulin pathway and response to oxidative stress play a major role in the genetics of human longevity: the lesson of centenarians
- Author
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Angelo Di Iorio, Giovanna De Benedictis, Fabiola Olivieri, Giuseppe Paolisso, Miriam Capri, Stefano Salvioli, Calogero Caruso, Silvana Valensin, Daniela Monti, Francesca Marchegiani, Maurizio Cardelli, Luca Cavallone, Claudio Franceschi, FRANCESCHI C, OLIVIERI F, MARCHEGIANI F, CARDELLI M, CAVALLONE L, CAPRI M, SALVIOLI S, VALENSIN S, DE BENEDICTIS G, DI IORIO A, CARUSO C, PAOLISSO G, MONTI, Franceschi C., Olivieri F., Marchegiani F., Cardelli M., Cavallone L., Capri M., Salvioli S., Valensin S., De Benedictis G., Di Iorio A., Caruso C., Paolisso G., Monti D., Franceschi, C, Olivieri, F, Marchegiani, F, Cardelli, M, Cavallone, L, Capri, M, Salvioli, S, Valensin, S, DE BENEDICTIS, G, DI IORIO, A, Caruso, C, Paolisso, Giuseppe, and Monti, D.
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Adult ,Senescence ,Aging ,Candidate gene ,Genotype ,media_common.quotation_subject ,Longevity ,Biology ,Models, Biological ,Genome ,Immune system ,Humans ,Insulin ,Insulin-Like Growth Factor I ,Gene ,Aged ,media_common ,Aged, 80 and over ,Inflammation ,Genetics ,Polymorphism, Genetic ,Aryldialkylphosphatase ,Interleukin-6 ,Age Factors ,Immunity ,Hedgehog signaling pathway ,Interleukin-10 ,Oxidative Stress ,Multigene Family ,Function (biology) ,Interleukin-1 ,Signal Transduction ,Developmental Biology - Abstract
In this paper, we review data of recent literature on the distribution in centenarians of candidate germ-line polymorphisms that likely affect the individual chance to reach the extreme limit of human life. On the basis of previous observations on the immunology, endocrinology and cellular biology of centenarians we focused on genes that regulate immune responses and inflammation (IL-6, IL-1 cluster, IL-10), genes involved in the insulin/IGF-I signalling pathway and genes that counteract oxidative stress (PON1). On the whole, data indicate that polymorphisms of these genes likely contribute to human longevity, in accord with observations emerging from a variety of animal models, and suggest that a common core of master genes and metabolic pathways are responsible for aging and longevity across animal species. Moreover, in the concern of our plan to discover new genetic factors related to longevity, we explored the possibility to by-pass the need of an a-priori choice of candidate genes, extending the search to genes and genomic regions of still unknown function. Alu sequences may be considered as good markers of highly variable and potentially unstable loci in functionally important genomic regions. We extensively screened Alu-rich genomic sites and found a new genomic region associated with longevity.
- Published
- 2005
35. Genes, Ageing and Longevity in Humans: Problems, Advantages and Perspectives
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Laura Celani, Stefano Salvioli, Miriam Capri, Francesca Marchegiani, G. De Benedictis, Calogero Caruso, Aurelia Santoro, Michele Mishto, Claudio Franceschi, Maurizio Cardelli, Giuseppe Paolisso, Efstathios S. Gonos, Fabiola Olivieri, Elena Bellavista, Elisa Cevenini, Laura Invidia, Daniela Monti, Federica Sevini, Francesco Lescai, Silvana Valensin, Salvioli S., Olivieri F., Marchegiani F., Cardelli M., Santoro A., Bellavista E., Mishto M., Invidia L., Capri M., Valensin S., Sevini F., Lescai F., Gonos E., Caruso C., Paolisso G., De Benedictis G., Monti D., Franceschi C., SALVIOLI S, OLIVIERI F, MARCHEGIANI F, CARDELLI M, SANTORO A, BELLAVISTA E, MISHTO M, INVIDIA L, CAPRI M, VALENSIN S, SEVINI F, CEVENINI E, CELANI L, LESCAI F, GONOS E, CARUSO C, PAOLISSO G, DE BENEDICTIS G, MONTI D, FRANCESCHI C, Salvioli, S, Olivieri, F, Marchegiani, F, Cardelli, M, Santoro, A, Bellavista, E, Mishto, M, Invidia, L, Capri, M, Valensin, S, Sevini, F, Cevenini, E, Celani, L, Lescai, F, Gonos, E, Caruso, C, Paolisso, Giuseppe, DE BENEDICTIS, G, Monti, D, and Franceschi, C.
- Subjects
Mitochondrial DNA ,Aging ,Proteasome Endopeptidase Complex ,Nuclear gene ,Apolipoproteins, genetics ,Insulin-Like Growth Factor I, genetics ,media_common.quotation_subject ,Apolipoprotein E4 ,Longevity ,Biology ,Genetic polymorphisms, ageing, longevity, centenarians, association studies, mitochondrial DNA ,Biochemistry ,DNA, Mitochondrial ,Inflammation, genetics ,Apolipoprotein E4, genetics ,Cytokines, genetics ,Animals ,Humans ,Allele ,Insulin-Like Growth Factor I ,Longevity, genetics ,Gene ,media_common ,Genetic association ,Genetics ,Aged, 80 and over ,Inflammation ,Polymorphism, Genetic ,Aryldialkylphosphatase ,Superoxide Dismutase ,Superoxide Dismutase, genetics ,General Medicine ,Clusterin, genetics ,Poly(ADP-ribose) Polymerases, genetics ,Aging, genetics ,Apolipoproteins ,Clusterin ,Tumor Suppressor Protein p53, genetics ,Genes ,Evolutionary biology ,Trait ,Cytokines ,Gene pool ,Poly(ADP-ribose) Polymerases ,Tumor Suppressor Protein p53 ,Aryldialkylphosphatase, genetics ,DNA, Mitochondrial, genetics ,Proteasome Endopeptidase Complex, physiology - Abstract
Many epidemiological data indicate the presence of a strong familial component of longevity that is largely determined by genetics, and a number of possible associations between longevity and allelic variants of genes have been described. A breakthrough strategy to get insight into the genetics of longevity is the study of centenarians, the best example of successful ageing. We review the main results regarding nuclear genes as well as the mitochondrial genome, focusing on the investigations performed on Italian centenarians, compared to those from other countries. These studies produced interesting results on many putative "longevity genes". Nevertheless, many discrepancies are reported, likely due to the population-specific interactions between gene pools and environment. New approaches, including large-scale studies using high-throughput techniques, are urgently needed to overcome the limits of traditional association studies performed on a limited number of polymorphisms in order to make substantial progress to disentangle the genetics of a trait as complex as human longevity.
- Published
- 2006
36. Invecchiamento e longevità come risultato dell'interazione tra genetica e ambiente
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FRANCESCHI, CLAUDIO, CAPRI, MIRIAM, SALVIOLI, STEFANO, VALENSIN, SILVANA, GUERESI, PAOLA, Monti D., FRANCESCHI C. CAPRI M. SALVIOLI S. VALENSIN S. MONTI D. GUERESI P. CARUSO C. BIOLO G. BARAZZONI R., Franceschi C., Capri M., Salvioli S., Valensin S., Monti D., and Gueresi P.
- Published
- 2004
37. The network and the remodeling theories of aging: historical background and new perspectives
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Silvana Valensin, Daniela Monti, Giuseppe Paolisso, Massimiliano Bonafè, Anatoli I. Yashin, G. De Benedictis, Claudio Franceschi, Franceschi, C, Valensin, S, Bonafe, M, Paolisso, Giuseppe, Yashin, Ai, Monti, D, and DE BENEDICTIS, G.
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Inflammation ,Gerontology ,Aging ,media_common.quotation_subject ,Longevity ,Saccharomyces cerevisiae ,Cell Biology ,Immunosenescence ,Biology ,Biological Evolution ,Biochemistry ,Network theory of aging ,Mice ,Multicellular organism ,Endocrinology ,Immune System ,Genetics ,Animals ,Humans ,Molecular Biology ,Neuroscience ,Heat-Shock Proteins ,media_common - Abstract
Two general theories, i.e. “the network theory of aging” (1989) and “the remodeling theory of aging” (1995), as well as their implications, new developments, and perspectives are reviewed and discussed. Particular attention has been paid to illustrate: (i) how the network theory of aging fits with recent data on aging and longevity in unicellular organisms (yeast), multicellular organisms (worms), and mammals (mice and humans); (ii) the evolutionary and experimental basis of the remodeling theory of aging (immunological, genetic, and metabolic data in healthy centenarians, and studies on the evolution of the immune response, stress and inflammation) and its recent development (the concepts of “immunological space” and “inflamm-aging”); (iii) the profound relationship between these two theories and the data which suggest that aging and longevity are related, in a complex way, to the capability to cope with a variety of stressors.
- Published
- 2000
38. Design, recruitment, logistics, and data management of the GEHA (Genetics of Healthy Ageing) project
- Author
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C. Gilbault, G. Pelicci, Marian Beekman, Axel Skytthe, Serena Dato, A. Skouteri, Konstantinos Voutetakis, Luca Deiana, Ciriaco Carru, Ewa Sikora, Claudio Franceschi, Friederike Flachsbart, Leena Peltonen, James W. Vaupel, P. Laiho, Joanna Collerton, V. Bezrukov, Stefan Schreiber, Michel Poulain, Karen Davies, Irene Maeve Rea, Mikko Hurme, Giuseppe Passarino, Federica Sevini, Katarzyna Broczek, Outi Törnwall, Antti Hervonen, Elisa Cevenini, Hélène Blanché, Bernard Jeune, Maria Scurti, Rodolfo Cotichini, Jean-Marie Robine, Erica Haimes, A.J.M. de Craen, Thomas B. L. Kirkwood, R. Masciulli, José Remacle, Lene Christiansen, Dorota Janiszewska, F. Balard, Almut Nebel, A. Leon, P.E. Slagboom, Lars Bolund, A. Marchisio, Liana Spazzafumo, Marja Jylhä, Virgilia Toccaceli, G. De Benedictis, Markus Perola, Olivier Toussaint, Jutta Gampe, M A Stazi, Silvana Valensin, Peter Kristensen, Kaare Christensen, Efstathios S. Gonos, University of Southern Denmark (SDU), University of Bologna/Università di Bologna, Laboratoire Lorrain de Sciences Sociales (2L2S), Université de Lorraine (UL), Institut National de la Santé et de la Recherche Médicale (INSERM), Netherlands Consortium for Healthy Ageing, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Institute of Gerontology [Kiev], Fondation Jean Dausset - Centre d’Etudes du Polymorphisme Humain [Paris] (CEPH), Beijing Genomics Institute [Shenzhen] (BGI), Institute of Human Genetics [Aarhus], Nencki Institute of Experimental Biology, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Medical University of Warsaw - Poland, Università degli Studi di Sassari = University of Sassari [Sassari] (UNISS), Odense University Hospital (OUH), Newcastle University [Newcastle], Istituto Superiore di Sanità (ISS), Universiteit Leiden, Università della Calabria [Arcavacata di Rende] (Unical), Institute of Clinical Molecular Biology, Kiel University, Max Planck Institute for Demographic Research (MPIDR), Max-Planck-Gesellschaft, Université Catholique de Louvain = Catholic University of Louvain (UCL), National Hellenic Research Foundation [Athens], Tampere School of Public Health, University of Tampere [Finland], University of Aarhus, The National Institute for Health and Welfare, National Institute for Health and Welfare [Helsinki], Research Innovation [Italy], IFOM Institute of Milan, Queen's University [Belfast] (QUB), Eppendorf Array Technologies, CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société (CERMES3 - UMR 8211 / U988 / UM 7), École des hautes études en sciences sociales (EHESS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Istituto Nazionale Ricovero e Cura Anziani, Université de Namur [Namur] (UNamur), European Project: 26813,GEHA, University of Bologna, Istituto Superiore di Sanita [Rome], University of Calabria, The Queen’s University of Belfast, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-École des hautes études en sciences sociales (EHESS), Skytthe A., Valensin S., Jeune B., Cevenini E., Balard F., Beekman M., Bezrukov V., Blanche H., Bolund L., Broczek K., Carru C., Christensen K., Christiansen L., Collerton J.C., Cotichini R., de Craen A.J., Dato S., Davies K., De Benedictis G., Deiana L., Flachsbart F., Gampe J., Gilbault C., Gonos E.S., Haimes E., Hervonen A., Hurme M.A., Janiszewska D., Jylha M., Kirkwood T.B., Kristensen P., Laiho P., Leon A., Marchisio A., Masciulli R., Nebel A., Passarino G., Pelicci G., Peltonen L., Perola M., Poulain M., Rea I.M., Remacle J., Robine J.M., Schreiber S., Scurti M., Sevini F., Sikora E., Skouteri A., Slagboom P.E., Spazzafumo L., Stazi M.A., Toccaceli V., Toussaint O., Tornwall O., Vaupel J.W., Voutetakis K., Franceschi C., GEHA consortium [Pini Elisa, Palmas Maria Giustina, Panourgia Maria Panagiota], balard, frédéric, and GEnetics for Healthy Aging - GEHA - 26813 - OLD
- Subjects
Research design ,Gerontology ,Male ,Questionnaires ,Aging ,Genetic Linkage ,[SDV]Life Sciences [q-bio] ,Genome-wide association study ,Biochemistry ,Nonagenarian sib pairs ,[SHS]Humanities and Social Sciences ,0302 clinical medicine ,Endocrinology ,Cognition ,Surveys and Questionnaires ,80 and over ,Medicine ,ComputingMilieux_MISCELLANEOUS ,media_common ,Genetics ,Aged, 80 and over ,0303 health sciences ,Life style ,Longevity ,Middle Aged ,HEALTHY AGING ,[SDV] Life Sciences [q-bio] ,Europe ,Research Design ,Extreme longevity tracking ,Female ,[SHS] Humanities and Social Sciences ,media_common.quotation_subject ,Article ,03 medical and health sciences ,Healthy ageing ,Humans ,Family ,Molecular Biology ,Life Style ,030304 developmental biology ,Genetic association ,Aged ,nonagenarian sib pair ,business.industry ,Patient Selection ,Cell Biology ,Multicenter study ,business ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
In 2004, the integrated European project GEHA (Genetics of Healthy Ageing) was initiated with the aim of identifying genes involved in healthy ageing and longevity. The first step in the project was the recruitment of more than 2500 pairs of siblings aged 90years or more together with one younger control person from 15 areas in 11 European countries through a coordinated and standardised effort. A biological sample, preferably a blood sample, was collected from each participant, and basic physical and cognitive measures were obtained together with information about health, life style, and family composition. From 2004 to 2008 a total of 2535 families comprising 5319 nonagenarian siblings were identified and included in the project. In addition, 2548 younger control persons aged 50-75years were recruited. A total of 2249 complete trios with blood samples from at least two old siblings and the younger control were formed and are available for genetic analyses (e.g. linkage studies and genome-wide association studies). Mortality follow-up improves the possibility of identifying families with the most extreme longevity phenotypes. With a mean follow-up time of 3.7years the number of families with all participating siblings aged 95years or more has increased by a factor of 5 to 750 families compared to when interviews were conducted. Thus, the GEHA project represents a unique source in the search for genes related to healthy ageing and longevity. In 2004, the integrated European project GEHA (Genetics of Healthy Ageing) was initiated with the aim of identifying genes involved in healthy ageing and longevity. The first step in the project was the recruitment of more than 2500 pairs of siblings aged 90years or more together with one younger control person from 15 areas in 11 European countries through a coordinated and standardised effort. A biological sample, preferably a blood sample, was collected from each participant, and basic physical and cognitive measures were obtained together with information about health, life style, and family composition. From 2004 to 2008 a total of 2535 families comprising 5319 nonagenarian siblings were identified and included in the project. In addition, 2548 younger control persons aged 50-75years were recruited. A total of 2249 complete trios with blood samples from at least two old siblings and the younger control were formed and are available for genetic analyses (e.g. linkage studies and genome-wide association studies). Mortality follow-up improves the possibility of identifying families with the most extreme longevity phenotypes. With a mean follow-up time of 3.7years the number of families with all participating siblings aged 95years or more has increased by a factor of 5 to 750 families compared to when interviews were conducted. Thus, the GEHA project represents a unique source in the search for genes related to healthy ageing and longevity.
- Published
- 2011
39. Systems biology and longevity: an emerging approach to identify innovative anti-aging targets and strategies
- Author
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Stefano Salvioli, Paolo Tieri, Miriam Capri, Elena Bellavista, Alexey Zaikin, Mirko Francesconi, Francesco Lescai, Aurelia Santoro, Silvana Valensin, Daniela Monti, Michele Mishto, Claudio Franceschi, Elisa Cevenini, J. P. de Magalhaes, Gastone Castellani, Cevenini E., Bellavista E., Tieri P., Castellani G., Lescai F., Francesconi M., Mishto M., Santoro A., Valensin S., Salvioli S., Capri M., Zaikin A., Monti D., de Magalhaes J.P., and Franceschi C.
- Subjects
Senescence ,Aging ,Process (engineering) ,Systems biology ,media_common.quotation_subject ,Longevity ,Genomics ,Computational biology ,Longevity, physiology ,Biology ,Protein degradation ,Models, Biological ,03 medical and health sciences ,0302 clinical medicine ,Drug Discovery ,Humans ,Organism ,030304 developmental biology ,media_common ,Pharmacology ,Genetics ,0303 health sciences ,Systems Biology ,Age Factors ,Phenotype ,Aging, physiology ,Drug Design ,030217 neurology & neurosurgery - Abstract
Human aging and longevity are complex and multi-factorial traits that result from a combination of environmental, genetic, epigenetic and stochastic factors, each contributing to the overall phenotype. The multi-factorial process of aging acts at different levels of complexity, from molecule to cell, from organ to organ systems and finally to organism, giving rise to the dynamic "aging mosaic". At present, an increasing amount of experimental data on genetics, genomics, proteomics and other -omics are available thanks to new high-throughput technologies but a comprehensive model for the study of human aging and longevity is still lacking. Systems biology represents a strategy to integrate and quantify the existing knowledge from different sources into predictive models, to be later tested and then implemented with new experimental data for validation and refinement in a recursive process. The ultimate goal is to compact the new acquired knowledge into a single picture, ideally able to characterize the phenotype at systemic/organism level. In this review we will briefly discuss the aging phenotype in a systems biology perspective, showing four specific examples at different levels of complexity, from a systemic process (inflammation) to a cascade-process pathways (coagulation) and from cellular organelle (proteasome) to single gene-network (PON-1), which could also represent targets for anti-aging strategies.
- Published
- 2010
40. The extreme longevity: the state of the art in Italy
- Author
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FRANCESCHI, CLAUDIO, CAPRI, MIRIAM, SALVIOLI, STEFANO, VALENSIN, SILVANA, Motta L., Motta M., Malaguarnera M., Vasto S., Candore G., Caruso C., Capurso A., Panza F., Solfrizzi V., D'Introno A., Colacicco A. M., Capurso S., Bennati E., Maugeri D., Rapisarda R., Franzone A., Ferlito L., De Benedictis G., Berardelli M., Masotti G., Petruzzi E., Petruzzi I., Pinzani P., Monti D., Antonini F. M., Capurso C., Nicita Mauro V., Lo Balbo C., Mento A., Nicita Mauro C., Maltese G., Basile G., Mari D., Coppola R., Provenzano R., Salvioli G., Baldelli M. V., Mussi C., Varricchio M., Barbieri M., Gambardella A., Paolisso G., Colonna Romano G., Lio D., Sansoni P., Vescovini R., Galli C., Biasini C., Telera A., Passeri G., Passeri M., Ferrari E., Cravello L., Barili L., Solerte S. B., Fioravanti M., Magri F., Fagnoni F., Senin U., Mecocci P., Cherubini A., Marigliano V., Tafaro L., Cicconetti P., Tombesi F., Tombolillo M. T., Ettore E., Forconi S., Boschi S., Righi G. A., Guerrini M., Giarelli L., Stanta G., Ferrucci L., Ble A., Metter E. J., Guralnik J. M., Pacifici R., Zuccaro P., Palmi I., Branca S., Fradà G., Motta F., Crimi G., FRANCESCHI C, MOTTA L, MOTTA M, MALAGUARNERA M, CAPRI M, VASTO S, CANDORE G, CARUSO C, IMUSCE, Franceschi C., Motta L., Motta M., Malaguarnera M., Capri M., Vasto S., Candore G., Caruso C., Capurso A., Panza F., Solfrizzi V., D'Introno A., Colacicco A.M., Capurso S., Salvioli S., Valensin S., Bennati E., Maugeri D., Rapisarda R., Franzone A., Ferlito L., De Benedictis G., Berardelli M., Masotti G., Petruzzi E., Petruzzi I., Pinzani P., Monti D., Antonini F.M., Capurso C., Nicita-Mauro V., Lo Balbo C., Mento A., Nicita-Mauro C., Maltese G., Basile G., Mari D., Coppola R., Provenzano R., Salvioli G., Baldelli M.V., Mussi C., Varricchio M., Barbieri M., Gambardella A., Paolisso G., Colonna-Romano G., Lio D., Sansoni P., Vescovini R., Galli C., Biasini C., Telera A., Passeri G., Passeri M., Ferrari E., Cravello L., Barili L., Solerte S.B., Fioravanti M., Magri F., Fagnoni F., Senin U., Mecocci P., Cherubini A., Marigliano V., Tafaro L., Cicconetti P., Tombesi F., Tombolillo M.T., Ettore E., Forconi S., Boschi S., Righi G.A., Guerrini M., Giarelli L., Stanta G., Ferrucci L., Ble A., Metter E.J., Guralnik J.M., Pacifici R., Zuccaro P., Palmi I., Branca S., Fradà G., Motta F., and Crimi G.
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Gerontology ,Male ,Aging ,media_common.quotation_subject ,Health Status ,Longevity ,Biochemistry ,Endocrinology ,State (polity) ,Development economics ,Genetics ,Diabetes Mellitus ,Medicine ,Humans ,Molecular Biology ,media_common ,Aged, 80 and over ,business.industry ,Cell Biology ,Gene Expression Regulation ,Italy ,Cardiovascular Diseases ,Immune System ,Extreme longevity tracking ,Female ,business - Published
- 2008
41. Complexity of anti-immunosenescence strategies in humans
- Author
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Michela Pierini, Serena Altilia, Federica Sevini, Francesco Lescai, Silvana Valensin, Rita Ostan, Claudio Franceschi, Daniela Monti, Laura Bucci, Miriam Capri, Stefano Salvioli, Capri M., Monti D., Salvioli S., Lescai F., Pierini M., Altilia S., Sevini F., Valensin S., Ostan R., Bucci L., and Franceschi C.
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Aging ,T-Lymphocytes ,Biomedical Engineering ,Medicine (miscellaneous) ,Cytomegalovirus ,Cytomegalovirus, immunology ,Bioengineering ,Thymus Gland ,Biology ,Immune System, growth /&/ development ,Biomaterials ,Immune system ,Antigen ,Thymus Gland, immunology ,Cytotoxic T cell ,Humans ,Involution (medicine) ,Cytomegalovirus Infections, immunology ,Progenitor cell ,Antigens ,Inflammation ,Thymic involution ,Inflammation, immunology ,T-Lymphocytes, immunology ,CD28 ,General Medicine ,Immunosenescence ,Aging, immunology ,Biological Evolution ,Immune System ,Immunology ,Cytomegalovirus Infections ,Antigens, immunology - Abstract
Immunosenescence is characterized by three main aspects: (i) the shrinkage of the T cell repertoire and the accumulation of oligoclonal expansions (megaclones) of memory/effector cells directed toward ubiquitary infectious agents; (ii) the involution of the thymus and the exhaustion of naive T cells; and (iii) a chronic inflammatory status called inflamm-aging. We present here possible strategies to counteract these main aspects of immunosenescence in humans with particular attention to the reduction of antigenic load by pathogens, such as CMV, and the normalization of intestinal microflora, the possible utilization of IL-7 to reverse thymic involution, the purging of megaclones, the forced expression of CD28 on T lymphocytes, the reduction of inflamm-aging and the administration of nutrients such as vitamin D. Possible drawbacks of all these strategies are discussed. Finally, the complexity of a rejuvenation approach is stressed, with particular attention to the inhibitory role played by the "old microenvironment" on the performance of progenitor cells, the best candidate to counteract the decline in regenerative potential characteristic of organs and tissues from old organisms.
- Published
- 2006
42. Inflamm-aging, Cytokines and aging: State of the art, new hypotheses on the role of mitochondria and new perspectives from systems biology
- Author
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Enzo Ottaviani, Claudio Franceschi, Daniela Monti, Silvana Valensin, Paolo Tieri, Stefano Salvioli, Miriam Capri, Salvioli S., Capri M., Valensin S., Tieri P., Monti D., Ottaviani E., and Franceschi C.
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Senescence ,Aging ,Systems biology ,media_common.quotation_subject ,In silico ,medicine.medical_treatment ,pro-inflammatory cytokines ,aging ,Physiology ,Disease ,Computational biology ,Biology ,Heat shock protein ,Drug Discovery ,medicine ,Animals ,Humans ,Phylogeny ,media_common ,Inflammation ,Pharmacology ,Polymorphism, Genetic ,Innate immune system ,Systems Biology ,Longevity ,Mitochondria ,Cytokine ,Cytokines - Abstract
In this article we summarise present knowledge on the role of pro-inflammatory cytokines on chronic inflammation leading to organismal aging, a phenomenon we proposed to call "inflamm-aging". In particular, we review genetic data regarding polymorphisms of genes encoding for cytokines and proteins involved in natural immunity (such as Toll-like Receptors and Heat Shock Proteins) obtained from large population studies including young, old and very old people in good health status or affected by age-related diseases such as Alzheimer's Disease and Type II Diabetes. On the whole, despite some controversial results, the available data are in favour of the hypothesis that pro-inflammatory cytokines play an important role in aging and longevity. Further, we present a possible hypothesis to reconcile energetic dysfunction, including mitochondria, and inflamm-aging. New perspectives for future studies, including phylogenetic studies in animal models and in silico studies on mathematical and bioinformatic models inspired by the systems biology approach, are also proposed.
- Published
- 2006
43. The genetics of human longevity
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Daniela Monti, Federica Sevini, Stefano Salvioli, Giovanna De Benedictis, Claudio Franceschi, Graham Pawelec, Miriam Capri, Laura Celani, Silvana Valensin, Efstathios S. Gonos, Capri M., Salvioli S., Sevini F., Valensin S., Celani L., Monti D., Pawelec G., De Benedictis G., Gonos E.S., and Franceschi C.
- Subjects
Aging ,PPARγ ,medicine.disease_cause ,Genome ,Pleiotropy ,Insulin ,Insulin-Like Growth Factor I ,p53, p66shc ,Aged, 80 and over ,Genetics ,Mutation ,General Neuroscience ,TLR-4 ,Apolipoprotein ,Longevity gene ,Interleukin-10 ,Multigene Family ,IL-10 ,Signal Transduction ,TGF-β ,Src Homology 2 Domain-Containing, Transforming Protein 1 ,Longevity ,Context (language use) ,Biology ,General Biochemistry, Genetics and Molecular Biology ,History and Philosophy of Science ,CETP ,medicine ,Humans ,Epigenetics ,PON1 ,Gene ,Adaptor Proteins, Signal Transducing ,Glycoproteins ,Genetic association ,Inflammation ,IL-6 ,insulin/IGF-1 ,Polymorphism, Genetic ,Aryldialkylphosphatase ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,IL-1 cluster ,Lipid Metabolism ,Cholesterol Ester Transfer Proteins ,PPAR gamma ,Toll-Like Receptor 4 ,Oxidative Stress ,Apolipoproteins ,Shc Signaling Adaptor Proteins ,TNF-α ,Tumor Suppressor Protein p53 ,Carrier Proteins ,Interleukin-1 ,Human mitochondrial DNA haplogroup - Abstract
Aging is due to a complex interaction of genetic, epigenetic, and environmental factors, but a strong genetic component appears to have an impact on survival to extreme ages. In order to identify "longevity genes" in humans, different strategies are now available. In our laboratory, we performed association studies on a variety of "candidate" polymorphisms in Italian centenarians. Many genes/polymorphisms gave negative results, while others showed a positive association with human longevity and a sometimes-positive association with unsuccessful aging (myocardial infarction, Alzheimer's disease, and type 2 diabetes). Results regarding genes involved in inflammation (IL-1 cluster, IL-6, IL-10, TNF-alpha, TGF-beta, TLR-4, PPARgamma), insulin/IGF-1 signaling pathway and lipid metabolism (apolipoproteins, CETP, PON1), and oxidative stress (p53, p66(shc)) will be described. In addition, a strong role of the interaction between nuclear and mitochondrial genomes (mtDNA haplogroups and the C150T mutation) emerged from our findings. Thus, the genetics of human longevity appears to be quite peculiar in a context where antagonistic pleiotropy can play a major role and genes can have a different biological role at different ages.
- Published
- 2006
44. Quantifying the relevance of different mediators in the human immune cell network
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Paolo Tieri, Vito Latora, Claudio Franceschi, Massimo Marchiori, Daniel Remondini, Silvana Valensin, Gastone Castellani, TIERI P, VALENSIN S, LATORA V, CASTELLANI G., MARCHIORI M, REMONDINI D, FRANCESCHI C., P. Tieri, S. Valensin, V. Latora, G. Castellani, M. Marchiori, D. Remondini, and C. Franceschi
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Statistics and Probability ,Chemokine ,Cell type ,medicine.medical_treatment ,animal diseases ,Molecular Networks (q-bio.MN) ,Antigen-Presenting Cells ,Inflammation ,chemical and pharmacologic phenomena ,Antigen-Antibody Complex ,Cell Communication ,Biochemistry ,Immune system ,Immunity ,medicine ,Humans ,Quantitative Biology - Molecular Networks ,Computer Simulation ,Lymphocytes ,NETWORK ,Molecular Biology ,Innate immune system ,biology ,CYTOKINES ,Models, Immunological ,biochemical phenomena, metabolism, and nutrition ,Acquired immune system ,Immunity, Innate ,Computer Science Applications ,Computational Mathematics ,Cytokine ,Computational Theory and Mathematics ,Gene Expression Regulation ,FOS: Biological sciences ,Immunology ,biology.protein ,bacteria ,medicine.symptom ,Inflammation Mediators ,IMMUNE SYSTEM ,Neuroscience ,Signal Transduction - Abstract
Immune cells coordinate their efforts for the correct and efficient functioning of the immune system (IS). Each cell type plays a distinct role and communicates with other cell types through mediators such as cytokines, chemokines and hormones, among others, that are crucial for the functioning of the IS and its fine tuning. Nevertheless, a quantitative analysis of the topological properties of an immunological network involving this complex interchange of mediators among immune cells is still lacking. Here we present a method for quantifying the relevance of different mediators in the immune network, which exploits a definition of centrality based on the concept of efficient communication. The analysis, applied to the human immune system, indicates that its mediators significantly differ in their network relevance. We found that cytokines involved in innate immunity and inflammation and some hormones rank highest in the network, revealing that the most prominent mediators of the IS are molecules involved in these ancestral types of defence mechanisms highly integrated with the adaptive immune response, and at the interplay among the nervous, the endocrine and the immune systems., Comment: 10 pages, 3 figures
- Published
- 2004
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45. Robust and cost-effective CRISPR/Cas9 gene editing of primary tumor B cells in Eµ-TCL1 model of chronic lymphocytic leukemia.
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Del Prete R, Drago R, Nardi F, Bartolini G, Bellini E, De Rosa A, Valensin S, and Kabanova A
- Abstract
Competing Interests: The authors declare no conflict of interest.
- Published
- 2024
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46. Are periodontitis and psoriasis associated? A pre-clinical murine model.
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Marruganti C, Gaeta C, Falciani C, Cinotti E, Rubegni P, Alovisi M, Scotti N, Baldi A, Bellan C, Defraia C, Fiorino F, Valensin S, Bellini E, De Rosa A, D'Aiuto F, and Grandini S
- Subjects
- Animals, Mice, Random Allocation, Male, Tumor Necrosis Factor-alpha blood, Interleukin-17 blood, Alveolar Bone Loss pathology, Alveolar Bone Loss etiology, Osteoclasts pathology, Psoriasis complications, Psoriasis pathology, Periodontitis complications, Periodontitis pathology, Disease Models, Animal, Mice, Inbred C57BL, Imiquimod
- Abstract
Aim: To investigate the bidirectional influence between periodontitis and psoriasis, using the respective experimental models of ligature- and imiquimod-induced diseases on murine models., Materials and Methods: Thirty-two C57/BL6J mice were randomly allocated to four experimental groups: control (P- Pso-), ligature-induced periodontitis (P+ Pso-), imiquimod-induced psoriasis (P- Pso+) and periodontitis and psoriasis (P+ Pso+). Samples (maxilla, dorsal skin and blood) were harvested immediately after death. Measures of periodontitis (distance between the cemento-enamel junction and alveolar bone crest [CEJ-ABC] and the number of osteoclasts) and psoriasis (epidermal thickness and infiltrate cell [/0.03mm
2 ]) severity as well as systemic inflammation (IL-6, IL-17A, TNF-α) were collected., Results: The P+ Pso+ group exhibited the most severe experimental periodontitis and psoriasis, with the highest values of CEJ-ABC, number of osteoclasts, epidermal thickness and infiltrate cells in the dorsal skin, as well as the highest blood cytokine concentration. The P+ Pso- group presented with higher cell infiltrate (/0.03mm2 ) compared to the control group (p <.05), while the P- Pso+ group showed substantially higher alveolar bone loss (CEJ-ABC) than the control group (p <.05)., Conclusions: Experimental periodontitis may initiate and maintain psoriasiform skin inflammation and, vice versa, experimental psoriasis may contribute to the onset of periodontitis. In a combined model of the diseases, we propose a bidirectional association between periodontitis and psoriasis via systemic inflammation., (© 2024 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)- Published
- 2024
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47. Anti-Tumor Efficacy of In Situ Vaccination Using Bacterial Outer Membrane Vesicles.
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Caproni E, Corbellari R, Tomasi M, Isaac SJ, Tamburini S, Zanella I, Grigolato M, Gagliardi A, Benedet M, Baraldi C, Croia L, Di Lascio G, Berti A, Valensin S, Bellini E, Parri M, Grandi A, and Grandi G
- Abstract
In situ vaccination (ISV) is a promising cancer immunotherapy strategy that consists of the intratumoral administration of immunostimulatory molecules (adjuvants). The rationale is that tumor antigens are abundant at the tumor site, and therefore, to elicit an effective anti-tumor immune response, all that is needed is an adjuvant, which can turn the immunosuppressive environment into an immunologically active one. Bacterial outer membrane vesicles (OMVs) are potent adjuvants since they contain several microbe-associated molecular patterns (MAMPs) naturally present in the outer membrane and in the periplasmic space of Gram-negative bacteria. Therefore, they appear particularly indicted for ISV. In this work, we first show that the OMVs from E. coli BL21(DE3)Δ60 strain promote a strong anti-tumor activity when intratumorally injected into the tumors of three different mouse models. Tumor inhibition correlates with a rapid infiltration of DCs and NK cells. We also show that the addition of neo-epitopes to OMVs synergizes with the vesicle adjuvanticity, as judged by a two-tumor mouse model. Overall, our data support the use of the OMVs in ISV and indicate that ISV efficacy can benefit from the addition of properly selected tumor-specific neo-antigens.
- Published
- 2023
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48. Outer Membrane Vesicles From The Gut Microbiome Contribute to Tumor Immunity by Eliciting Cross-Reactive T Cells.
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Tomasi M, Caproni E, Benedet M, Zanella I, Giorgetta S, Dalsass M, König E, Gagliardi A, Fantappiè L, Berti A, Tamburini S, Croia L, Di Lascio G, Bellini E, Valensin S, Licata G, Sebastiani G, Dotta F, Armanini F, Cumbo F, Asnicar F, Blanco-Míguez A, Ruggiero E, Segata N, Grandi G, and Grandi A
- Abstract
A growing body of evidence supports the notion that the gut microbiome plays an important role in cancer immunity. However, the underpinning mechanisms remain to be fully elucidated. One attractive hypothesis envisages that among the T cells elicited by the plethora of microbiome proteins a few exist that incidentally recognize neo-epitopes arising from cancer mutations ("molecular mimicry (MM)" hypothesis). To support MM, the human probiotic Escherichia coli Nissle was engineered with the SIINFEKL epitope (OVA- E.coli Nissle) and orally administered to C57BL/6 mice. The treatment with OVA- E.coli Nissle, but not with wild type E. coli Nissle, induced OVA-specific CD8
+ T cells and inhibited the growth of tumors in mice challenged with B16F10 melanoma cells expressing OVA. The microbiome shotgun sequencing and the sequencing of TCRs from T cells recovered from both lamina propria and tumors provide evidence that the main mechanism of tumor inhibition is mediated by the elicitation at the intestinal site of cross-reacting T cells, which subsequently reach the tumor environment. Importantly, the administration of Outer Membrane Vesicles (OMVs) from engineered E. coli Nissle, as well as from E. coli BL21(DE3)Δ ompA , carrying cancer-specific T cell epitopes also elicited epitope-specific T cells in the intestine and inhibited tumor growth. Overall, our data strengthen the important role of MM in tumor immunity and assign a novel function of OMVs in host-pathogen interaction. Moreover, our results pave the way to the exploitation of probiotics and OMVs engineered with tumor specific-antigens as personalized mucosal cancer vaccines., Competing Interests: GG, AGr, LF, AG, EK, IZ, and MT are co-inventors of one or more patents on OMVs; AGr and GG are involved in BiOMViS Srl interested in exploiting the OMV platform. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor MB declared a shared affiliation with the author ER at the time of review., (Copyright © 2022 Tomasi, Caproni, Benedet, Zanella, Giorgetta, Dalsass, König, Gagliardi, Fantappiè, Berti, Tamburini, Croia, Di Lascio, Bellini, Valensin, Licata, Sebastiani, Dotta, Armanini, Cumbo, Asnicar, Blanco-Míguez, Ruggiero, Segata, Grandi and Grandi.)- Published
- 2022
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49. Proteome-minimized outer membrane vesicles from Escherichia coli as a generalized vaccine platform.
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Zanella I, König E, Tomasi M, Gagliardi A, Frattini L, Fantappiè L, Irene C, Zerbini F, Caproni E, Isaac SJ, Grigolato M, Corbellari R, Valensin S, Ferlenghi I, Giusti F, Bini L, Ashhab Y, Grandi A, and Grandi G
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- Animals, Antigens, Bacterial immunology, Antigens, Bacterial metabolism, Bacterial Outer Membrane Proteins metabolism, Biological Transport, CD8-Positive T-Lymphocytes immunology, Escherichia coli Infections immunology, Escherichia coli Infections microbiology, Humans, Interleukin-6 metabolism, Mice, Proteome metabolism, Recombinant Proteins immunology, Recombinant Proteins metabolism, Synthetic Biology methods, Toll-Like Receptor 2 metabolism, Vaccine Development methods, Bacterial Outer Membrane immunology, Bacterial Outer Membrane metabolism, Bacterial Vaccines, Escherichia coli immunology, Escherichia coli metabolism, Extracellular Vesicles immunology, Extracellular Vesicles metabolism
- Abstract
Because of their potent adjuvanticity, ease of manipulation and simplicity of production Gram-negative Outer Membrane Vesicles OMVs have the potential to become a highly effective vaccine platform. However, some optimization is required, including the reduction of the number of endogenous proteins, the increase of the loading capacity with respect to heterologous antigens, the enhancement of productivity in terms of number of vesicles per culture volume. In this work we describe the use of Synthetic Biology to create Escherichia coli BL21(DE3)Δ60, a strain releasing OMVs (OMVs
Δ60 ) deprived of 59 endogenous proteins. The strain produces large quantities of vesicles (> 40 mg/L under laboratory conditions), which can accommodate recombinant proteins to a level ranging from 5% to 30% of total OMV proteins. Moreover, also thanks to the absence of immune responses toward the inactivated endogenous proteins, OMVsΔ60 decorated with heterologous antigens/epitopes elicit elevated antigens/epitopes-specific antibody titers and high frequencies of epitope-specific IFN-γ-producing CD8+ T cells. Altogether, we believe that E. coli BL21(DE3)Δ60 have the potential to become a workhorse factory for novel OMV-based vaccines., Competing Interests: Guido Grandi, Alberto Grandi, Enrico König, Ilaria Zanella, Laura Fantappiè and Carmela Irene are co‐inventors of patents on OMVs; Alberto Grandi and Guido Grandi are involved in a biotech company interested in exploiting the OMV platform., (© 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)- Published
- 2021
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50. Bacterial outer membrane vesicles engineered with lipidated antigens as a platform for Staphylococcus aureus vaccine.
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Irene C, Fantappiè L, Caproni E, Zerbini F, Anesi A, Tomasi M, Zanella I, Stupia S, Prete S, Valensin S, König E, Frattini L, Gagliardi A, Isaac SJ, Grandi A, Guella G, and Grandi G
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- Animals, Bacterial Outer Membrane immunology, Bacterial Outer Membrane metabolism, Bacterial Outer Membrane Proteins immunology, Bacterial Outer Membrane Proteins metabolism, Escherichia coli genetics, Escherichia coli metabolism, Female, Lipopolysaccharides immunology, Mice, Staphylococcal Infections immunology, Staphylococcal Infections microbiology, Antigens, Bacterial immunology, Bacterial Vaccines immunology, Extracellular Vesicles immunology, Staphylococcal Infections prevention & control, Staphylococcus aureus immunology
- Abstract
Bacterial outer membrane vesicles (OMVs) represent an interesting vaccine platform for their built-in adjuvanticity and simplicity of production process. Moreover, OMVs can be decorated with foreign antigens using different synthetic biology approaches. However, the optimal OMV engineering strategy, which should guarantee the OMV compartmentalization of most heterologous antigens in quantities high enough to elicit protective immune responses, remains to be validated. In this work we exploited the lipoprotein transport pathway to engineer OMVs with foreign proteins. Using 5 Staphylococcus aureus protective antigens expressed in Escherichia coli as fusions to a lipoprotein leader sequence, we demonstrated that all 5 antigens accumulated in the vesicular compartment at a concentration ranging from 5 to 20% of total OMV proteins, suggesting that antigen lipidation could be a universal approach for OMV manipulation. Engineered OMVs elicited high, saturating antigen-specific antibody titers when administered to mice in quantities as low as 0.2 μg/dose. Moreover, the expression of lipidated antigens in E. coli BL21(DE3)Δ ompA Δ msbB Δ pagP was shown to affect the lipopolysaccharide structure, with the result that the TLR4 agonist activity of OMVs was markedly reduced. These results, together with the potent protective activity of engineered OMVs observed in mice challenged with S. aureus Newman strain, makes the 5-combo-OMVs a promising vaccine candidate to be tested in clinics., Competing Interests: Conflict of interest statement: G. Grandi, L. Fantappiè, and C.I. are coinventors of a patent on OMVs; A. Grandi and G. Grandi are involved in a biotech company interested in exploiting the OMV platform., (Copyright © 2019 the Author(s). Published by PNAS.)
- Published
- 2019
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