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1. Insights Into Sibling Relationships and Longevity From Genetics of Healthy Ageing Nonagenarians: The Importance of Optimisation, Resilience and Social Networks

Author

Jennifer Nicola M. Rea, Katarzyna Milana Broczek, Elisa Cevenini, Laura Celani, Susanne Alexandra J. Rea, Ewa Sikora, Claudio Franceschi, Vita Fortunati, and Irene Maeve Rea

Subjects
nonagenarian siblings, nonagenarian sibling relationships, Gold typologies, coping strategies, optimism, resilience, Psychology, BF1-990
Abstract

Understanding how to “Age Longer and Age Well” is a priority for people personally, for populations and for government policy. Approximately ten percent of nonagenarians reach 90 years and beyond in good condition and seem to have a combination of both age-span and health-span. However, the factors which contribute to human longevity remain challenging. Culture is a shared system of learning ideas, feelings, and survival strategies. It has a strong influence on each person’s psychological development, behavior, values and beliefs. Nonagenarians have rich life experiences that can teach us much about aging well; they are rich reservoirs of genetic, lifestyle and psychological information which can help understanding about how to live longer and better. Sibling or trio nonagenarians are important sources of family beliefs and behaviors upon which individual personalities may have been built. Their personal family histories and narratives are powerful tools that help to determine familial traits, beliefs and social behaviors which may help establish factors important in the siblings’ longevity. Using purposefully selected subjects, recruited to the Genetics of Healthy Ageing (GeHA) project in four European countries, this research used the simple life story and qualitative research methods to analyze contrasting and distinctive questions about the interface between the psychological and social worlds as presented in the nonagenarian siblings’ insights about their longevity. Their stories aimed to give better understanding about which psychological aspects of their common life journey and the degree of emotional support in their sibling relationships may have supported their paths to longevity. The most universal finding in each of the four European countries was that nonagenarians demonstrated high positivity, resilience and coping skills and were supported in social networks. Around this theme, nonagenarians reported “being happy,” “always cheerful,” “never melancholy” and having a contentment with a “rich life” and family relationships which fits with accumulating evidence that life satisfaction comes from a perceived self-efficacy and optimism. Most sibling relationships in this study, when analyzed according to the Gold classification, fit the “congenial” or “loyal” relationship type – demonstrating a healthy respect for the others’ opinion without overt dependence, which may help individual coping and survival mechanisms.

Published
2022
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2. Prompting medical students to self–assess their learning needs during the ageing and health module: a mixed methods study

Author

Grace Kennedy, Jennifer Nicola M. Rea, and Irene Maeve Rea

Subjects
medical students, self-assessment, learning outcomes, quantitative and qualitative methods, ageing and health module, Special aspects of education, LC8-6691, Medicine (General), R5-920
Abstract

Understanding our learning needs is fundamental for safe, effective and knowledge-based medical practice and facilitates life-long learning. A mixed methods study investigated fourth-year medical students’ self-perceived understanding of their learning needs using 1] a visual scale, before and after a four-week module in Ageing and Health (A&H) and 2] through focus group discussions. During 2013–14 academic year, all students (252) were invited to use a Visual Analogue Scale (VAS) tool to self-assess their learning needs that were linked to Ageing and Health curriculum learning outcomes. Assenting students (197 at pre-self-assessment, 201 at post-assessment) returned anonymous Visual Analogue Scales, self-assessing history-taking skills, examination skills, knowledge of medication use, co-morbidity, nutritional and swallowing assessment responses, before and after the A&H module. Three student focus groups explored whether completion of the VAS self-assessment had prompted improved self-awareness of their learning needs. The VAS responses increased for each curriculum domain with significant differences between the pre-and post responses – for the student-year-group. Nutritional and swallowing knowledge showed the greatest improvement from a self-assessed low baseline at entry. Focus-group students generally viewed the VAS tool positively, and as an aid for prompting consideration of current and future clinical practice. Some students recognised that ‘a need to be ready-for-work’ focused engaged learning; others demonstrated self-regulated learning through self-motivation and an action plan. The Visual Analogue Scale quantitative responses showed increased student-self-perceived learning for each curriculum domain at fourth-year completion of the A&H module, suggesting that prompting self-assessment had increased students’ knowledge and skills. Focus group students saw the VAS tool as useful for prompting awareness of their current and future learning needs. Additional educational strategies should be explored to enable all students to self-reflect and engage effectively on their learning needs, to gain the skills for the maintenance of professional medical competence. Abbreviations: A&H: Ageing and Health Module; e-portfolio: an electronic version of an evidence portfolio, which allows medical students and graduates to reflect and document learning and competencies; F1: year1 of post-graduate medical clinical training; GMC: General Medical Council-the regulation organisation for maintaining standards for doctors in UK; Logbook: usually a written document which can be used to record procedures and attendance at clinics or case-based discussions and can be used to set learning outcomes and to structure teaching in clinical settings for medical students and doctors; PDP: personal development plan is used to plan future learning and skills needs for work and education with an plan for action/s outcome; SPSS: Statistical Package for the Social Sciences; VAS: Visual Analogue Scale is a visual method of describing an experience.

Published
2019
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3. Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines

Author

Irene Maeve Rea, David S. Gibson, Victoria McGilligan, Susan E. McNerlan, H. Denis Alexander, and Owen A. Ross

Subjects
aging, age-related diseases, inflamm-aging, redox, SASP, autophagy, Immunologic diseases. Allergy, RC581-607
Abstract

Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called “inflamm-aging.” Despite research there is no clear understanding about the causes of “inflamm-aging” that underpin most major age-related diseases, including atherosclerosis, diabetes, Alzheimer’s disease, rheumatoid arthritis, cancer, and aging itself. While inflammation is part of the normal repair response for healing, and essential in keeping us safe from bacterial and viral infections and noxious environmental agents, not all inflammation is good. When inflammation becomes prolonged and persists, it can become damaging and destructive. Several common molecular pathways have been identified that are associated with both aging and low-grade inflammation. The age-related change in redox balance, the increase in age-related senescent cells, the senescence-associated secretory phenotype (SASP) and the decline in effective autophagy that can trigger the inflammasome, suggest that it may be possible to delay age-related diseases and aging itself by suppressing pro-inflammatory molecular mechanisms or improving the timely resolution of inflammation. Conversely there may be learning from molecular or genetic pathways from long-lived cohorts who exemplify good quality aging. Here, we will discuss some of the current ideas and highlight molecular pathways that appear to contribute to the immune imbalance and the cytokine dysregulation, which is associated with “inflammageing” or parainflammation. Evidence of these findings will be drawn from research in cardiovascular disease, cancer, neurological inflammation and rheumatoid arthritis.

Published
2018
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4. Towards ageing well: Use it or lose it: Exercise, epigenetics and cognition

Author

Irene Maeve Rea

Subjects
0301 basic medicine, Gerontology, Aging, medicine.medical_specialty, Health Status, Longevity, Physical exercise, Disease, Brain-derived neurotrophic factor, Epigenesis, Genetic, Healthy Aging, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), Cognition, SDG 3 - Good Health and Well-being, Mitochondrial biogenesis, Intervention (counseling), Healthy ageing, medicine, Journal Article, Animals, Humans, Genetic Predisposition to Disease, Muscle, Skeletal, Exercise, Aged, 80 and over, business.industry, Public health, Brain, Exercise-induced stress response, Epigenome, Lifestyle, 030104 developmental biology, Phenotype, Ageing, Cognitive Aging, Quality of Life, Epigenetics, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Research Article
Abstract

More and more people are living into the 90s or becoming centenarians. But, the gift of increased 'age span' seldom equates with an improved 'health-span'. Governments across the world are expressing concern about the epidemic of chronic disease, and have responded by initiating policies that make prevention, reduction and treatment of chronic disease, a public health priority. But understanding, how to age long and well, with the avoidance of chronic disease and later life complex disease morbidity is challenging. While inherited genes have an undoubted role to play in the chance of maintaining good health or conversely a predilection to developing disease and chronic ill health, there is increasing evidence that behavioural and environmental life-style choices may contribute up to 50% of the variability of human lifespan. Physical exercise is readily available to everyone, and is a simple cheap and effective form of life-style intervention. Exercise appears to help maintain good health and to reduce the risk of developing chronic disease and ill health. Evidence suggests that physical activity improves well-being across many health domains through out life, continues to offer important health benefits in older age groups and tracks with a 'healthy ageing' profile. Although many of the molecular pathways remain to be fully identified, here we discuss how physical activity and exercise is understood to produce changes in the human epigenome, which have the potential to enhance cognitive and psychological health, improve muscular fitness, and lead to better ageing with improved quality of life in older age.

Published
2017
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5. Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age

Author

Doris Lechner, Miriam Capri, Stefan Böhringer, Stefan Schreiber, Gonneke Willemsen, Paolo Garagnani, Irene Maeve Rea, Andres Metspalu, Palmi V. Jonsson, Thomas B. L. Kirkwood, Lene Christiansen, Fernando Rivadeneira, Giuseppina Rose, J. Wouter Jukema, Serena Dato, Owen A. Ross, Almut Nebel, Cornelia M. van Duijn, Gary Saunders, Bernard Jeune, David J. Stott, Jeanine J. Houwing-Duistermaat, A. Murphy, Anton J. M. de Craen, Friederike Flachsbart, Karen Andersen-Ranberg, Albert Hofman, Ian Ford, Ellen A. Nohr, Giuseppe Passarino, Krista Fischer, Elisa Cevenini, Carmen Martin-Ruiz, Jutta Gampe, Iris Postmus, Christopher P. Nelson, Stefano Salvioli, Alberto Montesanto, Mark Lathrop, Marianne Nygaard, Marie E. Breen, Jennifer Harrow, Hae-Won Uh, Erik B. van den Akker, Thorkild I. A. Sørensen, André G. Uitterlinden, Alexander Viktorin, Bastiaan T. Heijmans, Susan E. McNerlan, Quinta Helmer, Naveed Sattar, Claudio Franceschi, Eco J. C. de Geus, E. Mihailov, Jouke-Jan Hottenga, Qihua Tan, Kari Stefansson, Yoichiro Kamatani, Paolina Crocco, Henning Tiemeier, Stella Trompet, Patrik K. E. Magnusson, Marian Beekman, Riin Tamm, Amke Caliebe, Maris Alver, Femke-Anouska Heinsen, Pilar Galan, Daníel F. Guðbjartsson, Joris Deelen, Linda Broer, Ruud van der Breggen, Kristin L. Ayers, Anna M. Bennet, Dorret I. Boomsma, P. Eline Slagboom, Kaare Christensen, Diana van Heemst, Joanna Collerton, Karen Davies, Rudi G. J. Westendorp, Hélène Blanché, Lavinia Paternoster, Nilesh J. Samani, Hreinn Stefansson, Simon P. Mooijaart, Heather J. Cordell, Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), LeidenUniversity Medical Centre, Department of Epidemiology, The Netherlands Cancer Institute, Institute of Genetic Medicine, Newcastle University [Newcastle], National Institute of Public Health, University of Southern Denmark (SDU), Department of Clinical Genetics, Odense University Hospital, Fondation Jean Dausset - Centre d’Étude du Polymorphisme Humain, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University of Tartu, Institute of Molecular and Cell Biology, Department of Gerontology and Geriatrics, Leiden University Medical Center (LUMC), deCODE genetics [Reykjavik], Christian-Albrechts University of Kiel, University of Calabria, Delft University of Technology (TU Delft), Department of Cardiovascular Sciences, Université Catholique de Louvain = Catholic University of Louvain (UCL), University Hospitals Leicester, Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], School of Medicine, Dentistry and Biomedical Sciences [Belfast], Queen's University [Belfast] (QUB), University of Iowa [Iowa City], DIMES: Department of Experimental, Diagnostic and Specialty Medicine, Bologna University Hospital, Institute for Ageing and Health, University of Glasgow, Max Planck Institute for Demographic Research (MPIDR), Max-Planck-Gesellschaft, Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), EMGO Institute for Health and Care Research, VU University Amsterdam Medical Center, Landspitali National University Hospital of Iceland, University of Iceland, McGill University = Université McGill [Montréal, Canada], Genome Quebec Innovation Centre, Institut de Génomique, Belfast Health and Social Care Trust, Estonian Biocentre, Partenaires INRAE, Aarhus University [Aarhus], School of Social and Community Medicine, Erasmus University Rotterdam, Mayo Clinic, BHF Glasgow Cardiovascular Research Centre, University Medical Center Schleswig-Holstein, Institute of Cardiovascular and Medical Sciences, Sophia Children's Hospital, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Augustinus Foundation, Avera Institute for Human Genetics (AIHG), AXA Research Fund, Belfast City Hospital Trust Fund, Biobanking and Biomolecular Resources Research Infrastructure (BBMRI -NL) [184.021.007], Biotechnology and Biological Sciences Research Council (BBSRC), Bristol-Myers Squibb, Center for Inherited Disease Research (CIDR), Centre for Medical Systems Biology (CMSB), CERA Foundation, Commissariat a L'Energie Atomique (CEA)-Centre National de Genotypage (CNG), Danish Agency for Science, Technology and Innovation (DASTI)/The Danish Council for Independent Research (DCIR) [11-107308], Danish National Research Foundation (DNRF), Department of Health and Social Services (Northern Ireland), DFG-Cluster of Excellence 'Inflammation at Interfaces', Dunhill Medical Trust [R124/0509], Egmont Foundation, Estonian Science Foundation [7859], Estonian Government [SF0180142s08], European Research Council (ERC) [230374], European Science Foundation (ESF) [EU/QLRT-2001-01254], European Union [FP5-QLK6-CY-2001-00128, FP6-LIFESCIHEALTH-36894, FP6-LSH M-CT-2004-503270, FP7-HEALTH-2007-B-223004, FP7-HEALTH-F4-2007-201413, FP7-HEALTH-F4-2008-202047, FP7-HEALTH-2009-single-stage-242244, FP7-HEALTH-2010-two-stage-259679], Fondation Caisse d'Epargne Rhone-Alpes Lyon CERAL, Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health (NIMH) [MH081802], GenomEUtwin [EU/QLRT-2001-01254, QLG2-CT-2002-01254], Guy's & St Thomas' NHS Foundation Trust, Health Foundation, Heart and Lung foundation [20070481], Innovation-Oriented Research Program on Genomics (SenterNovem) [IGE05007], Institut National de la Recherche Agronomique (INRA), Institut National de la Sante et de la Recherche Medicale (INSERM), King's College London, Medical Research Council (MRC) [G0500997, G0601333], Ministere de l'Enseignement superieur et de la Recherche (MESR), National Institutes of Health (NIH)/National Institute of Aging (NIA) [P01AG08761, R01D0042157-01A, U01DK066134], National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre, NBIC BioAssist [NWO-NBIC/BioAssist/RK/2008.024], Netherlands Consortium for Healthy Ageing (NCHA) [050-060-810], Netherlands Genomics Initiative (NGI), Netherlands Heart Foundation (NHF) [2001 D 032], Netherlands Organization for Scientific Research (NWO, MagW/ZonMW) [904-61-090, 904-61-193, 480-04-004, 400-05-717, Spinozapremie 56-464-14192, 175.010.2005.011, 911-03-012, 985-10-002, Addiction-31160008, Middelg-root-911-09-032], Netspar - Living longer for a good health, NHS North of Tyne (Newcastle Primary Care Trust), Pharmacy Foundation, Regione Autonoma della Sardegna, Rutgers University Cell and DNA Repository [NIMH U24 MH068457-06], Swedish Research Council [M-2005-1112], Tampere University Hospital and Academy of Finland, Danish Interdisciplinary Research Council, Health Foundation (Helsefonden), Ministry for Higher Education, National Program for Research Infrastructure [09-063256], March of Dimes Birth Defects Foundation, Swedish Foundation for Strategic Research (SSF), Unilever Discover Colworth, Universite Paris 13, University of Tartu [SP1GVAR-ENG], Velux Foundation, VU University's Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA), Wellcome Trust [084762, 085475, 087436], IDEAL [FP7-HEALTH-2010-two-stage-259679], Research and Education into Ageing-0153, European Regional Development Fund, Deelen J, Beekman M, Uh HW, Broer L, Ayers KL, Tan Q, Kamatani Y, Bennet AM, Tamm R, Trompet S, Guðbjartsson DF, Flachsbart F, Rose G, Viktorin A, Fischer K, Nygaard M, Cordell HJ, Crocco P, van den Akker EB, Böhringer S, Helmer Q, Nelson CP, Saunders GI, Alver M, Andersen-Ranberg K, Breen ME, van der Breggen R, Caliebe A, Capri M, Cevenini E, Collerton JC, Dato S, Davies K, Ford I, Gampe J, Garagnani P, de Geus EJ, Harrow J, van Heemst D, Heijmans BT, Heinsen FA, Hottenga JJ, Hofman A, Jeune B, Jonsson PV, Lathrop M, Lechner D, Martin-Ruiz C, McNerlan SE, Mihailov E, Montesanto A, Mooijaart SP, Murphy A, Nohr EA, Paternoster L, Postmus I, Rivadeneira F, Ross OA, Salvioli S, Sattar N, Schreiber S, Stefánsson H, Stott DJ, Tiemeier H, Uitterlinden AG, Westendorp RG, Willemsen G, Samani NJ, Galan P, Sørensen TI, Boomsma DI, Jukema JW, Rea IM, Passarino G, de Craen AJ, Christensen K, Nebel A, Stefánsson K, Metspalu A, Magnusson P, Blanché H, Christiansen L, Kirkwood TB, van Duijn CM, Franceschi C, Houwing-Duistermaat JJ, Slagboom PE., Leiden Univ, Dept Mol Epidemiol, NL-2300 RC Leiden, Netherlands [ 2 ] Leiden Univ, Netherlands Consortium Healthy Ageing, NL-2300 RC Leiden, Netherlands [ 3 ] Leiden Univ, Dept Med Stat & Bioinformat, NL-2300 RC Leiden, Netherlands [ 4 ] Leiden Univ, Dept Cardiol, NL-2300 RC Leiden, Netherlands [ 5 ] Leiden Univ, Dept Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands [ 6 ] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands [ 7 ] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands [ 8 ] Newcastle Univ, Int Ctr Life, Inst Med Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England [ 9 ] Univ So Denmark, Inst Publ Hlth, DK-5000 Odense C, Denmark [ 10 ] Univ So Denmark, Inst Clin Res, Dept Gynecol & Obstet, DK-5000 Odense C, Denmark [ 11 ] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark [ 12 ] Odense Univ Hosp, Clin Biochem & Pharmacol, DK-5000 Odense C, Denmark [ 13 ] Fdn Jean Dausset CEPH, F-75010 Paris, France [ 14 ] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden [ 15 ] Univ Tartu, Estonian Genome Ctr, Tartu 51010, Estonia [ 16 ] Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia [ 17 ] deCODE Genet, Populat Gen, IS-101 Reykjavik, Iceland [ 18 ] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany [ 19 ] Univ Kiel, Inst Med Informat & Stat, D-24105 Kiel, Germany [ 20 ] Univ Calabria, Dept Biol Ecol & Earth Sci, I-87036 Arcavacata Di Rende, Italy [ 21 ] Delft Univ Technol, Delft Bioinformat Lab, NL-2600 GA Delft, Netherlands [ 22 ] Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England [ 23 ] Glenfield Hosp, Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, Leicester LE3 9QP, Leics, England [ 24 ] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England [ 25 ] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Belfast BT9 7BL, Antrim, North Ireland [ 26 ] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA [ 27 ] Univ Bologna, Dept Expt Diagnost & Specialty Med, I-40126 Bologna, Italy [ 28 ] Univ Bologna, Interdepartmental Ctr L Galvani, I-40126 Bologna, Italy [ 29 ] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England [ 30 ] Univ Glasgow, Robertson Ctr Biostat, Glasgow G12 8QQ, Lanark, Scotland [ 31 ] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark, Scotland [ 32 ] Max Planck Inst Demograf Forsch, Lab Stat Demog, D-18057 Rostock, Germany [ 33 ] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands [ 34 ] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, NL-1081 BT Amsterdam, Netherlands [ 35 ] Landspitali Univ Hosp, IS-101 Reykjavik, Iceland [ 36 ] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland [ 37 ] CEA, Inst Genom, F-91057 Evry, France [ 38 ] McGill Univ, Montreal, PQ H3G 1A4, Canada [ 39 ] Genome Quebec Innovat Ctr, Montreal, PQ H3G 1A4, Canada [ 40 ] Belfast Hlth & Social Care Trust, Cytogenet Lab, Belfast BT8 8BH, Antrim, North Ireland [ 41 ] Estonian Bioctr, EE-51010 Tartu, Estonia [ 42 ] Aarhus Univ, Dept Publ Hlth, Epidemiol Sect, DK-8000 Aarhus C, Denmark [ 43 ] Univ Bristol, Sch Social & Community Med, MRC Ctr Causal Anal Translat Epidemiol, Bristol BS8 2BN, Avon, England [ 44 ] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA [ 45 ] Univ Glasgow, Fac Med, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland [ 46 ] Univ Kiel, PopGen Biobank, D-24105 Kiel, Germany [ 47 ] Univ Hosp Schleswig Holstein, D-24105 Kiel, Germany [ 48 ] Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Child & Adolescent Psychiat, NL-3000 CA Rotterdam, Netherlands [ 49 ] Univ Paris 04, UREN, U557, INSERM, F-93017 Bobigny, France [ 50 ] U1125 Inra, F-93017 Bobigny, France [ 51 ] Cnam, F-93017 Bobigny, France [ 52 ] Univ Paris 13, CRNH IdF, F-93017 Bobigny, France [ 53 ] Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr, DK-2200 Copenhagen N, Denmark [ 54 ] Inst Prevent Med, DK-2000 Copenhagen, Denmark [ 55 ] Frederiksberg Univ Hosp, DK-2000 Copenhagen, Denmark [ 56 ] Interuniv Cardiol Inst Netherlands, NL-3501 DG Utrecht, Netherlands [ 57 ] Bellaria Hosp, IRCCS Inst Neurol Sci, I-40139 Bologna, Italy [ 58 ] CNR, ISOF, I-40129 Bologna, Italy, Epidemiology, Surgery, Internal Medicine, Child and Adolescent Psychiatry / Psychology, ProdInra, Migration, Vrije Universiteit Amsterdam [Amsterdam] (VU), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), VU University Amsterdam, Biological Psychology, and EMGO+ - Lifestyle, Overweight and Diabetes

Subjects
Male, Netherlands Twin Register (NTR), Disease/genetics, Lífslíkur, Longevity/genetics, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Genetic Linkage, Genome-wide association study, 0302 clinical medicine, Prospective Studies, Genetics (clinical), Genetics, Aged, 80 and over, 0303 health sciences, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Association Studies Articles, Age Factors, Chromosome Mapping, Genetic Loci/physiology, General Medicine, 3. Good health, Europe, Phenotype, Cardiovascular Diseases, Hypertension, Chromosomes, Human, Pair 5, Female, Human Longevity, genetics, meta-analysis, Aging/genetics, Cardiology and Cardiovascular Medicine, HUMAN AGING, Longevity, European Continental Ancestry Group, Population, HUMAN GENETICS, Single-nucleotide polymorphism, Locus (genetics), Biology, FAMILIAL LONGEVITY, White People, 03 medical and health sciences, Gene mapping, SDG 3 - Good Health and Well-being, Cardiovascular Diseases/genetics, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Allele, education, Molecular Biology, Aged, 030304 developmental biology, Genetic association, Öldrun, Genome, Human, Arfgengi, Minor allele frequency, Ageing, Genetic Loci, Chromosomes, Human, Pair 19, Hypertension/genetics, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Genome-Wide Association Study
Abstract

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. The genetic contribution to the variation in human lifespan is ∼ 25%. Despite the large number of identified disease-susceptibility loci, it is not known which loci influence population mortality. We performed a genome-wide association meta-analysis of 7729 long-lived individuals of European descent (≥ 85 years) and 16 121 younger controls (

Published
2014
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6. Design, recruitment, logistics, and data management of the GEHA (Genetics of Healthy Ageing) project

Author

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
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7. Genetics of healthy aging in Europe: the EU-integrated project GEHA (GEnetics of Healthy Aging)

Author

Olivier Toussaint, Bernard Jeune, Thomas B. L. Kirkwood, M A Stazi, James W. Vaupel, P.E. Slagboom, Hélène Blanché, Michel Poulain, Jean-Marie Robine, Ewa Sikora, Pier Giuseppe Pelicci, Antti Hervonen, Lars Bolund, V. Bezrukov, Liana Spazzafumo, Irene Maeve Rea, A. Leon, Luca Deiana, José Remacle, Huanning Yang, Stefan Schreiber, Peter Kristensen, Kaare Christensen, Efsthatios Gonos, Giovanna De Benedictis, Claudio Franceschi, Leena Peltonen, Franceschi C., Bezrukov V., Blanché H., Bolund L., Christensen K., de Benedictis G., Deiana L., Gonos E., Hervonen A., Yang H., Jeune B., Kirkwood T.B., Kristensen P., Leon A., Pelicci P.G., Peltonen L., Poulain M., Rea I.M., Remacle J., Robine J.M., Schreiber S., Sikora E., Slagboom P.E., Spazzafumo L., Stazi M.A., Toussaint O., and Vaupel J.W.

Subjects
Adult, medicine.medical_specialty, Linkage disequilibrium, Aging, Genetic Linkage, Genomics, Biology, Genetic analysis, DNA, Mitochondrial, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Linkage Disequilibrium, History and Philosophy of Science, Genetic linkage, Molecular genetics, Genotype, medicine, media_common.cataloged_instance, Animals, Humans, European Union, European union, media_common, Aged, Genetics, Aged, 80 and over, Genome, Models, Genetic, General Neuroscience, Linkage Disequilibrium Mapping, Linkage (Genetics), Middle Aged, Europe
Abstract

Udgivelsesdato: 2007-Apr The aim of the 5-year European Union (EU)-Integrated Project GEnetics of Healthy Aging (GEHA), constituted by 25 partners (24 from Europe plus the Beijing Genomics Institute from China), is to identify genes involved in healthy aging and longevity, which allow individuals to survive to advanced old age in good cognitive and physical function and in the absence of major age-related diseases. To achieve this aim a coherent, tightly integrated program of research that unites demographers, geriatricians, geneticists, genetic epidemiologists, molecular biologists, bioinfomaticians, and statisticians has been set up. The working plan is to: (a) collect DNA and information on the health status from an unprecedented number of long-lived 90+ sibpairs (n = 2650) and of younger ethnically matched controls (n = 2650) from 11 European countries; (b) perform a genome-wide linkage scannning in all the sibpairs (a total of 5300 individuals); this investigation will be followed by linkage disequilibrium mapping (LD mapping) of the candidate chromosomal regions; (c) study in cases (i.e., the 2650 probands of the sibpairs) and controls (2650 younger people), genomic regions (chromosome 4, D4S1564, chromosome 11, 11.p15.5) which were identified in previous studies as possible candidates to harbor longevity genes; (d) genotype all recruited subjects for apoE polymorphisms; and (e) genotype all recruited subjects for inherited as well as epigenetic variability of the mitochondrial DNA (mtDNA). The genetic analysis will be performed by 9 high-throughput platforms, within the framework of centralized databases for phenotypic, genetic, and mtDNA data. Additional advanced approaches (bioinformatics, advanced statistics, mathematical modeling, functional genomics and proteomics, molecular biology, molecular genetics) are envisaged to identify the gene variant(s) of interest. The experimental design will also allow (a) to identify gender-specific genes involved in healthy aging and longevity in women and men stratified for ethnic and geographic origin and apoE genotype; (b) to perform a longitudinal survival study to assess the impact of the identified genetic loci on 90+ people mortality; and (c) to develop mathematical and statistical models capable of combining genetic data with demographic characteristics, health status, socioeconomic factors, lifestyle habits.

Published
2007
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8. Genes and life-style factors in BELFAST nonagenarians: Nature, Nurture and Narrative

Author

Irene Maeve Rea, Jennifer Rea, H. Denis Alexander, Susan E. McNerlan, and Ashley Carvalho

Subjects
Genetic Markers, Male, Gerontology, Aging, Genotype, Health Status, Immunology, Longevity, Public policy, Review, Northern Ireland, Review Article, Motor Activity, Nature versus nurture, Social support, Narrative, Quality of life (healthcare), Risk Factors, Journal Article, Humans, Longitudinal Studies, Social Behavior, Life Style, Behavioural genetics, Aged, 80 and over, BELFAST nonagenarians, Personal narrative, Research Support, Non-U.S. Gov't, Age Factors, Social Support, Nurture, Causality, Nature, humanities, Diet, Ageing, Phenotype, Genes, Life-style, Quality of Life, Female, Gene-Environment Interaction, Geriatrics and Gerontology, Psychology, Risk Reduction Behavior
Abstract

Understanding how to 'Age Longer and Age Well' is a priority for people personally, for populations globally and for government policy. Nonagenarians are the oldest members of our societies and survivors of their generation. Approximately 10 % of nonagenarians reach 90 years and beyond in good condition and seem to have a combination of both age-span and health-span. But what are the factors which help people reach their ninetieth birthday and beyond in good condition? Are they genetics, as in 'nature', or do they depend on 'nurture' and are related to environment, or are both factors inextricably intertwined within the concept of behavioural genetics? Nonagenarians have rich life experiences that can teach us much about ageing well; they are reservoirs of genetic, life-style and behavioural information which can help dissect out how to live not only longer but better. Personal family history and narrative are powerful tools that help to determine familial traits, beliefs and social behaviours and when used in parallel with new biotechnology methods inform and elaborate causality. Here we present themes and insights from personal narrative enquiry from nonagenarian participants from the Belfast Elderly Longitudinal Free-living Ageing STudy (BELFAST) about factors they consider important for good quality ageing and relate these insights to the emerging genetics and life-style evidence associated with healthy longevity.

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