Beneficiaries

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UNIVERSITÄT KONSTANZ

Prof. Alexander Bürkle

The University of Konstanz was founded in 1966 as a “reform university” with new forms of study and
teaching and a new system of self-administration replacing traditional university structures. Research at
the University of Konstanz is highly renowned at the international level. Inter-disciplinary and international
cooperation, the comprehensive support of junior scientists, technology transfer and the close link
between research and teaching are guiding principles of the University. A series of national rankings
conducted over the last decade provide evidence for the University’s top-class achievements. In the
context of the “Excellence Initiative”, a nationwide research assessment exercise, the University of
Konstanz was recently identified as one out of 9 top-level universities in Germany.
Alexander Bürkle, MD is Full Professor and Chair of Molecular Toxicology at the University’s Dept of
Biology. His profile is described in detail on page 63. He is an expert in poly(ADP-ribosyl)ation and its
relevance for the ageing process (4). His group has recently established and successfully used a new,
robust FACS-based method for the determination of cellular poly(ADP-ribosyl)ation capacity (2,6). In
addition, his group has set up a new automated method to measure DNA strand breaks and strand break
repair in living cells (Brabeck et al., 2003; Moreno-Villanueva et al., submitted). Poly(ADP-ribosyl)ation
capacity and DNA strand break repair will be systematically determined in MARK-AGE proband samples.

WP1: Recruitment of probands and physiological markers 

WP2: DNA-based markers

WP8: Data analysis and bioinformatics

WP9: Dissemination and training

WP10: Project management and ethical issues

BioTeSys GmbH

Dr. Jürgen Bernhardt

BioTeSys GmbH was founded in Esslingen, Germany, in 1999. It is a spin-off of the institute of Biological
Chemistry and Nutrition, University of Hohenheim, Germany. The focus of this SME is on biological and
functional analysis of bioactive substances. This includes identification of the functional properties of
ingredients and their mixtures, and investigating effects and efficacy. As a complete service-provider in the
field of biological and chemical analysis, the company offers an outstanding range of services, including
the development of new techniques and products on behalf of customers from nutrition, cosmetic and
consumer health care industries.
The choice of technology includes screening methods covering analyses of the bioactive potential of
substances and mixtures by HPLC or photometry, in-vitro test systems based upon single cells, co-
cultures or organotypic models as well as the design, performance, monitoring and validation of clinical
studies.

WP1: Recruitment of probands and physiological markers

WP6: Oxidative stress markers Clinical chemistry, hormones and markers of metabolism

WP9: Dissemination and training

WP10: Project management and ethical issues

 

Fundación Centro Nacional de Investigaciones Oncológicas Carlos III

Dr. María A. Blasco

Dr. Blasco heads one of the world’s leading groups in telomere biology. This group forms part of the
Spanish National Cancer Centre (CNIO). CNIO’s scientific staff comprises about 400 persons active in
Molecular Pathology, Molecular Oncology, Experimental Therapeutics, Structural Biology & Biocomputing,
and Biotechnology. Dr Blasco has developed numerous mouse models that have provided a wealth of
data on the interplay between telomeric repeats, telomerase, and different telomere binding proteins and
the impact of their interactions on a wide range of cellular processes including chromosomal stability, gene
expression, cell replicative lifespan, and stem cell function. Current lines of research are addressing the
nature and functions of this interplay in the context of ageing and ageing-related pathologies.

WP2: DNA-based markers

WP9: Dissemination and training

WP10: Project management and ethical issues

 

DNage B.V.

Dr. Gerben Zondag

Dr. Zondag is Director Technology of DNage BV, and Head of Research of Pharming BV. He has a
background in molecular and cell biology, graduated in cancer research at the Netherlands Cancer
Institute and has been involved in corporate research since 2000.
DNage is a biotechnology company that focuses on the development of products for medical and health
problems associated with ageing. A key element of the company’s strategy is the development of novel
therapeutics and biomarkers in the field of ageing related disorders. To advance basic and applied
research, the company has exclusive access to unique tools including various progeroid mouse models
that show accelerated ageing. DNage’s main focus is the development of a therapy targeting Cockayne
Syndrome (“CS”), a relatively rare human disease where people suffer from accelerated ageing causing a
variety of ageing-associated diseases. Pre-clinical experiments using certain compounds have shown a
significant improvement in our animal models, which closely mimic the human condition.
DNage originated from the Erasmus MC Department of Genetics, and as such, can build upon a vast
experience and world-class scientists in the field of DNA damage/repair and ageing.
Within the MARK-AGE project, serum from progeroid patients and suitable control sera will be collected
and supplied to the consortium for testing against the standard panel of biomarkers. Results will be
compared to sera of normally ageing subjects, such as to test the universality of these biomarkers and
their ability to identify aging features independent of chronological age. At the same time it will help
determine to what extent CS and normal ageing resemble each other in this regard. Conversely, we will
search for novel biomarkers using serum of CS patients and the markers translated from rapidly ageing
CS(-like) mouse mutants (see project Erasmus MC), thus extending the panel of ageing-related
biomarkers.

WP1: Recruitment of probands and physiological markers 

WP7: Emergent biomarkers of ageing from model systems and novel methodological approaches

WP9: Dissemination and training

WP10: Project management and ethical issues

ERASMUS

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM

Prof. Jan Hoeijmakers

The Erasmus University Medical Center (Erasmus MC) is the largest medical institution in the Netherlands
providing top reference medical care to 3 million people and covering 22% of the country. The Center
excels internationally with forefront research in a range of important disciplines including cell biology and
genetics, epidemiology and others. It has a very strong, integrated basic, translational and clinical
research infrastructure with state-of-the-art technology such as genomics, proteomics, bioinformatics,
animal and sophisticated imaging facilities etc. Within the area of ageing research the institute harbors
leading groups in the fundamental, clinical and epidemiological fields, which are tightly integrated and with
numerous connections to other health care institutions, creating a world-class multidisciplinary nucleus
with highly synergistic added value.
The overall research theme of the Department of Genetics concerns mechanisms involved in genetic
(in)stability and their biological impact. The Dept. of Genetics (Prof Hoeijmakers, Dr van der Horst) is part
of the ‘Center for Biomedical Genetics’, which is recognized as the top research school in the Medical
Sciences in the Netherlands. One of the main research areas of the Department, the analysis of DNA
nucleotide excision repair (NER) in human disease, has a long tradition with the pioneering work of Drs.
Bootsma and Hoeijmakers, the former and present head of the Department. For their work these
investigators received the prestigious 1995 Louis Jeantet prize. In the early 90’s, the group successfully
entered the field of transgenesis and generated over 15 NER mouse models, many of which mimicking
XP/CS
, Xpd XP/CS , Xpd TTD ). This unique panel of
human progeroid NER syndromes (i.e. Csa, Csb, Ercc1, Xpb
mouse models stood at the basis of the discovery of the link between DNA damage, repair, transcription,
and ageing/longevity. Recent research highlights include the ‘omics’-based finding that prematurely aging
NER mice display systemic suppression of the GH/IGF1 somatotroph axis and oxidative metabolism,
along with an increased antioxidant response, in an attempt to minimize the production of genotoxic ROS,
and as a consequence, relieve the pressure on their genome and extend life span.
The activities of the group in aging research are widely acknowledged, as evident from the many
invitations to participate in meetings (e.g. GRC, CSH, Keystone) and granted research program proposals
(i.e. NWO, European Community, HFSP, NIH, etc.). Close contacts with the National Institute of Public
Health and the Environment (RIVM, Dr. H. van Steeg), exist already for many years as reflected in several
joint seminal publications.
The Hoeijmakers/van der Horst team (in close collaboration with the Dollé/van Steeg group), will use the
progeroid mouse models to develop a set of biomarkers for ageing in prematurely ageing mouse models
to deliver universal markers of ageing. These markers will be verified in material from the human
population study, and, conversely, we will verify biomarkers identified in human cohort studies by other
members of the MARK-AGE consortium, in the prematurely ageing mouse models.

WP7: Emergent biomarkers of ageing frommodel systems and novel methodological  approaches

WP9: Dissemination and training

WP10: Project management and ethical issues

Facultés Universitaires Notre-Dame de la Paix de Namur

Dr. Olivier Toussaint

The Facultés Universitaires Notre-Dame de la Paix (FUNDP) comprise five faculties and an Institute of
Computer Science with an academic and scientific staff of more than 600. There are more than a hundred
laboratories and research centres associated to the FUNDP. Research has priority status being present in
the most varied domains. Basic and applied research is conducted with links to specific applications,
especially in partnership with private companies or public regional, federal or supranational institutions.
O. Toussaint (OT) is Research Associate of the Belgian FNRS. OT is contractor of the FP6 Integrated
Project GEHA and member of its ethics board. His laboratory’s proteomics engineer (M. Dieu) identified
the trypanosome lytic factor of serum (Nature 2003, 422: 83-7) and identified 30 biomarker proteins
involved in senescence (FEBS Lett 2002, 531: 499-504) and age-related changes of abundance of
proteasome subunits (Int J Biochem Cell Biol 2003, 35: 728-39). OT participates in the FP6 IP
‘Proteomage’ and is co-ordinator of the FP6 European Coordination Action LINK-Age in molecular
gerontology, and as such in charge of organising four 100-persons high level conferences and two 30-
persons summer schools (www.link-age.eu/). In the past OT has coordinated a Shared-Cost Action on
functional genomics in human ageing (Functionage, 2002-4).
In the project ‘Senegene’, sponsored by the Region of Wallonia, OT recruits a population of aged blood
donors characterized by different levels of healthiness in order to perform transcriptional, proteomic and
functional studies, namely on T lymphocytes. In cooperation with that project, a dedicated, fully automated
culture station under physiological O 2 atmosphere has been constructed. This system allows studying the
stress response of cells from donors of different ages, namely the induction of senescence by stress. OT‘s
laboratory expertise in molecular biology allowed to develop a new technology of DNA arrays and
establish a company which became Eppendorf’s world center on genomics ( www.eppendorf.com/eat/en/),
allowing development of low-density DNA arrays and transcription factor DNA-binding assays OT is using
in research. The reliability of Eppendorf’s arrays is recognised in a multi-centre validation study (Nat
Biotechnol 2006, 24 :1151-61).
From year 2000 onwards OT published 51 Medline-referenced publications on the interactions between
exposure to short acute sublethal stress (oxidative agents, ethanol, UVB, etc.) and cell senescence. OT
coined ‘stress-induced premature senescence’ (SIPS) (EMBO J 2000, 19 :1929-34). OT has been invited
speaker at top-class international congresses on ageing research. He co-organized two Euroconferences
on Biological Ageing (2000 & 2002) and an EMBO Workshop Molecular Gerontology (1999).

WP1: Recruitment of probands and physiological markers

WP7: Emergent biomarkers of ageing frommodel systems and novel methodological approaches

WP9: Dissemination and training

WP10: Project management and ethical issues

Imperial College of Science, Technology and Medicine

Prof. Richard Aspinall

Imperial College of Science, Technology and Medicine is an independent constituent part of the University
of London.

WP4: Immunological markers

WP9: Dissemination and training

WP10: Project management and ethical issues

 

Österreichische Akademie der Wissenschaften

Prof. Beatrix Grubeck-Loebenstein

The Institute for Biomedical Aging Research (IBA) was founded in 1992 by the Austrian Academy of
Sciences and has the following specific research goals: (a) to study aging processes at the cellular level in
order better to understand age-related impairments/ diseases; (b) to define measures to postpone/prevent
age-related impairments/diseases to improve the quality of life in old age. The IBA consists of three
divisions (Immunology, Endocrinology and Molecular and Cell Biology). The goal of the Immunology
Division is to reach a better understanding of age-related changes within the immune system in order to
find new ways to prevent loss of immune function with age. Of practical relevance is the question how
vaccinations can be optimized for the elderly. The laboratory has all necessary infrastructure for state-of-
the-art molecular biology and cell biology research.

WP4: Immunological markers

WP9: Dissemination and training

WP10: Project management and ethical issues

Istituto Nazionale Riposo e Cura per Anziani

Dr. Eugenio Mocchegiani

The INRCA Institute operates in the sector of population ageing by addressing gerontological and geriatric
problems of the “third age” through biological, clinical, epidemiological and socio-economical studies.
Research at the Institute aims at improving the quality of life of the elderly population and can be divided
into three different interconnected sectors: (1) applied clinical research (Geriatric hospitals); (2) socio-
economical research (Socio-Economic Department); and (3) basic biogerontological research
(Gerontological Department). The Section “Nutrition and Immunosenescence” (Gerontol. Dept.) has
substantial experience in age-related changes related to zinc homeostasis and immunosenescence. The
goal of the Section “Nutrition and Immunosenescence” is to reach a better understanding of age-related
changes in micronutrients metabolism in order to find new ways to prevent age-related diseases.

WP6: Oxidative stress markers Clinical chemistry, hormones and markers of  metabolism

WP9: Dissemination and training

WP10: Project management and ethical issues

Nestlé S.A.

Dr. Sunil Kochhar

The team has a unique expertise in Nuclear Magnetic Resonance Spectroscopy (NMR), Mass
Spectrometry (MS) as well as stable isotope mass spectrometry analysis of biological fluids and tissues.
Nestlé Research Center (NRC) has established robust NMR and MS metabonomics platforms for
metabolic profiling and is recognized as leading expert in nutritional metabonomics. Metabonomics
research addresses the metabolic understanding of human with foods and its consequences in health
maintenance. The main scientific goal is to characterize the metabolic health of individuals in relation with
dietary patterns and environmental factors. This is particularly carried out through the metabolic
determination of the complex metabolic interactions between gut microbiota and host physiological
processes.
The “Metabonomics and Biomarkers” group of NRC comprises 15 senior scientists, post-doctoral fellows,
research students and technical support. From a technological aspect, the group has access to two high
resolution NMR (600MHz) spectrometers and various MS instruments (UPLC-TOF-MS, GC/GC-TOF-MS,
HPLC-MSn, GC-MS, GC-IRMS, HPLC-IRMS). In support to metabolic profiling capabilities, the team has
developed state-of-the art data mining routines for maximizing the recovery of key metabolic information
from the acquired complex metabolic profiles. This involved the use of multivariate statistics tools for
variable selection, data modelling and biomarker identification. Furthermore, the team is composed by
biologists, analytical chemists and statisticians, which is unique in joining complementary expertises for
data generation, analysis and biochemical interpretation. In addition, a metabolite database for the
identification of metabolites in complex biological matrices was established. The database includes a
collection of NMR monodimensional and bidimensional spectra of almost 300 metabolites reported in
human plasma and urine.

WP5: Clinical chemistry, hormones and markers of metabolism

WP8: Data analysis and bioinformatics

WP10: Project management and ethical issues

National Hellenic Research Foundation

Prof. Efstathios S. Gonos

The National Hellenic Research Foundation (NHRF) is one of the largest research foundations and a
Center of Excellence in Biology in Greece. It includes the Department of Molecular and Cellular Ageing
directed by Dr. Gonos. He has published over 70 research articles in eminent journals and author of
several monographs and patents holder. He has organized the 2 nd EuroConference on “Biological Ageing”
and the 12 th International Association of Biomedical Gerontology Congress. He is Associate Editor of
“Mechanisms of Ageing & Development” and Editorial board member of “Aging Cell”, “Experimental
Gerontology” and “Biogerontology”. He is member of several international committees and he has been
Deputy National Representative of Greece at the EU in FP-6/“Genomics and Biotechnology for Health”.
The research activities of the Department of Molecular and Cellular Ageing are focused on the genetic and
environmental factors that are linked to human ageing and longevity. They are financed by several
competitive research grants awarded by the EU, the Hellenic General Secretariat of Research &
Technology as well as by private sources. Specifically, by using functional genomics approaches several
genes have been cloned which associate with human ageing and longevity including clusterin/ApoJ. In
parallel, the general biochemical mechanisms that relate to ageing are also studied, with emphasis in the
function of the proteasome and its activation. Finally the Department possesses a collection of samples
(PBMC, skin fibroblasts) of donors of different ages, including healthy centenarians and long-lived siblings.
These samples are employed to study agents that delay the cellular ageing process as well as to identify
gene variants that are linked with longevity.

WP1: Recruitment of probands and physiological markers

WP3: Markers based on proteins and their modifications

WP9: Dissemination and training

WP10: Project management and ethical issues

Nencki Institute of Experimental Biology

Prof. Ewa Sikora

Nencki Insitute is the largest biological research centre in Poland with about 300 staff, with neurobiology
and biochemistry representing two main research areas. Its excellent publication record accounts for 20%
of all Polish author citations in international biological journals. The Institute is engaged in 15 international
projects, including 7 FP6 projects (one coordinated by Prof. Sikora). The Institute is home of 1 EU and 2
national Centres of Excellence in Neurobiology and Bioimaging. It receives assistance from the Office of
International Cooperation and Project Management. The Laboratory of Molecular Bases of Ageing has all
necessary infrastructure for state-of-the-art molecular and cell biology work. Techniques used routinely
include tissue culture, T cell cloning, confocal and fluorescent light microscopy, FACS analysis and cell
sorting, Southern, Northern and Western analysis, ELISAs, PCR, cDNA arrays, and cell transfection.

WP1: Recruitment of probands and physiological markers 

WP4: Immunological markers

WP9: Dissemination and training

WP10: Project management and ethical issues

Institutul National de Gerontologie si Geriatrie Ana Aslan

Prof. Daniela Gradinaru

The work programme will be carried out at the “Ana Aslan” National Institute of Gerontology and Geriatrics
(NIGG) and Geriatrics and “Carol Davila” University of Medicine and Pharmacy (UMF), Faculty of
Pharmacy, Department of Biochemistry-Toxicology, Bucharest.
Brief description of the organization: The first Institute of Geriatrics in the world was founded by
Professor Ana Aslan in Bucharest, Romania in 1952 and the World Health Organization acknowledged the
idea of an institute entirely dedicated to the study of medical, biological and social aspects of aging. The
institute is coordinated by the Ministry of Health and Family and the University of Medicine “Carol Davila”,
Bucharest. The main research areas are: age-related disorders, biology of aging, biomarkers of aging,
geriatric assessment, nutritional studies, and geronto-prophylaxis. The institute also provides healthcare
and psycho-social assistance for older people.

WP6: Oxidative stress markers Clinical chemistry, hormones and markers of metabolism

WP9: Dissemination and training

WP10: Project management and ethical issues

Rijksinstituut voor Volksgezondheid en Milieu

Ph.D Martijn Dollé

The RIVM is the principal research institute of the Dutch government, and is proactive, through basic and
applied research or in an advisory capacity, on all major areas of human health care and environmental
protection. It closely cooperates with international organizations (WHO, IARC, EU, ICPS, etc.) and
research groups world wide. The main tasks attributed to the RIVM are proband recruitment (WP1, Dr.
Verschuren), routine clinical chemistry determinations (WP4&5, Drs Jansen, Dollé and De Vries) and
novel biomarker detection using mouse models (WP7, Drs Van Steeg, Dollé and De Vries).
Dr. Martijn Dollé is working in the Laboratory for Toxicology, Pathology and Genetics as a project leader,
translating mouse model aging research to human population studies. His background is on DNA
instability in ageing animal models. Currently he is involved in various genetic association studies relating
gene variants to metabolic syndrome, cancer, cardiovascular disease and ageing in general, using diet as
an additional variable. His interests are to identify human critical pathways, biomarkers and intervention
strategies for age related chronic diseases.

WP1: Recruitment of probands and physiological markers

WP4: Immunological markers

WP5: Clinical chemistry, hormones and markers of metabolism

WP9: Dissemination and training

WP10: Project management and ethical issues

StratiCELL Screening Technologies SA/NV

Dr. Michel Salmon

StratiCELL is a SME and was created in 2005 based on in vitro models developed by Dr. M. Salmon and
N. Belot, who are now Directors at Straticell. N. Belot has gained experience in blood-related studies in a
regional project where recruitment of aged probands was the basis of research of biomarkers (proteomics,
transcriptomics, cytokine profiling) of non-recovery of aged patients suffering from conditions like
pneumonia, hip fracture or heart failure. StratiCELL (http://www.straticell.com/) is located in a new biotech
plant created by the Economical Bureau (http://www.crealys.be/crealys/en/incubators/index.asp) of the
Province of Namur.
The pharmaceutical, cosmetics and chemical industry and public laboratories need predictive and
reproducible in vitro skin equivalents and related assays enabling more accurate human skin responses
when screening efficacy and safety endpoints. The service activity comprises cell biology, in vitro
toxicology and efficacy services based on blood cells (multiplexing cytokine assay, diverse biochemical
assays), dermal fibroblasts, keratinocytes and 3D skin culture models for testing chemicals, drugs,
cosmetic ingredients and finished products (toxicity, irritation, sensitization, photoprotection, phototoxicity,
anti-ageing, etc.) without using animal models. The production activity relates to the manufacture of
biologically standardized human reconstituted epidermis and skin equivalents (transgenic or wild-type
cultures) based on powerful technological advantages. StratiCELL is a contractor of the EU FP6
Coordination Action LINK-Age and of the Marie Curie project “MATISS” aimed at testing in vitro the effects
of new plastic polymers on skin.
StratiCELL will contribute to MARK-AGE by performing analyses of gene expression profiles in
lymphocytes from defined ageing cohorts after exposure to non-physiological oxygen tensions.
StratiCELL has worked for CODIF International, a company developing active ingredients for the
cosmetics industry. Toxicity and efficacy analyses enabled patenting of a compound called
“Phycojuvenine”. In addition, StratiCELL has contributed to a study on 20-hydroxyecdysone, a new
ingredient to repair fibroblast damages caused by UV light in order to prevent their premature senescence.
StratiCELL performs R&D work based on (1) DNA arrays co-developed with Eppendorf Array
Technologies and recognised as reliable in a multi-center validation or with RT-PCR; (2) proteomic
analysis (2Dgels/LC-MS); and (3) functional analysis through overexpression or inactivation of genes
using in-vitro models.

WP4: Immunological markers

WP7: Emergent biomarkers of ageing from model systems and novel methodological approaches

WP10: Project management and ethical issues

Aarhus Universitet

Ph.D Peter Kristensen

The University of Aarhus is the second largest University in Denmark and consists of eight faculties. The
Department of Molecular Biology (MBI) within the Faculty of Science comprises a permanent scientific and
technical-administrative staff of 44 and 60, respectively, and a temporary scientific and technical-
administrative staff of approximately 71 and 24, respectively. The MBI Department is part of the Danish
Centre for Molecular Gerontology (DCMG), established in 1996. During the past 20 years the group has
been working on various aspects of molecular gerontology. This work was mainly focussed on the use of
in vitro cultivated eukaryotic cells in long term culture and was the basis for extensive experience in setting
up and maintaining human cells of various origin in culture. During the past 12 years the Department has
developed novel technologies for identification of proteins expressed differentially by certain cell types. In
relation to the studies on the genetics of healthy aging, a number of genes will be identified influencing
healthy aging and longevity. The group headed by Dr. Peter Kristensen specifically has a long standing
expertise in mammalian cell culture, 2D-PAGE, phage display and other molecular biology techniques.

WP7: Emergent biomarkers of ageing from model systems and novel methodological approaches

WP9: Dissemination and training

WP10: Project management and ethical issues

 

Aston University

Prof. Helen R. Griffiths

Aston University is a research led University focusing on relevant, rigorous research that will make a
substantial and beneficial difference to individuals, organisations and society in general . It comprises of
four Schools of study, including Life and Health Sciences (LHS). LHS research ranges from the molecular
and cellular levels, through neural systems and human behaviour, to the restoration of health and study of
people in health care and societal settings. Research expenditure has shown a year-on-year increase
since 2001 from major sponsors including MRC, BBSRC, EPSRC, ESRC, Wellcome Trust, UK/EU
government together with funding from many other charitable sources and industrial collaborators
supporting our strategy for growth. LHS employs 82 academic staff members with a postdoctoral and
postgraduate community of 50 and 80 individuals respectively. The University has supported LHS in
gaining the investment for more than £12M in research infrastructure over the past four years to create a
unique range of combined resources including a specialised proteomics facility.

WP7: Emergent biomarkers of ageing from model systems and novel methodological approaches

WP9: Dissemination and training

WP10: Project management and ethical issues

VIB logo jpg (for white background)

Flanders Institute for Biotechnology vzw

Prof. Claude Libert

VIB is a top-class centre of excellence comprising 800 scientists in 60 groups carrying out research at the
forefront of life sciences. Research at VIB is focused on the fundamental understanding of growth, normal
development and diseases. VIB has successfully coordinated or participated in a series of EU projects,
including Human Mobility projects, and two VIB laboratories were selected as research training sites.
Within the VIB, the Department for Molecular Biomedical Research (DMBR) has over 150 scientists active
in diverse fields of biotechnology (therapeutics production based on micro-organisms), oncology, and
inflammation biology. This unique mix of strong basic research on disease and translational research
makes this VIB department particularly suited for hosting the team of Aging Research.
Early studies on yeast cell death showed that some genes affect both cell death and the ageing process.
A sophisticated screening method was developed by Dr. Chen for identifying human genes influencing
ageing in yeast. This method selectively stains chitin in the bud scars and sorts out the more intensely
stained (older) cells by FACS technology (2). By using this method on cells expressing human genes, a
collection of human genes influencing ageing was identified, and some of them are being scrutinized (3).
In parallel, study of a yeast genomic overexpression library identified several genes, one of which was
studied further (4). Dr. Chen has recently broadened her interest to glycome in studying the ageing
process by using high-throughput N-glycan analytical technology developed in-house. Initial studies on
healthy human blood donors revealed that some N-glycan structures change with chronological age above
40 years of age (1). These studies were extended with older cohorts of Italian centenarians and a Werner
patient (5). Other glycomics studies were carried out on sera from rats and mice living under caloric
restriction or ad libitum conditions (manuscript in preparation).

WP3: Markers based on proteins and their modifications

WP9: Dissemination and training

WP10: Project management and ethical issues

Universität Hohenheim  (2006–2010)/

Friedrich Schiller University (2010–2014)

SOCIETY OF NUTRITION AND FOOD SCIENCE (2014 – today)

Prof. Tilman Grune

The University of Hohenheim is the leading German university in the field of agricultural sciences and
human nutrition. Prof Tilman Grune heads the Department of ‘Biofunctionality and Safety of Food’ and is
implicated in several teaching programmes. The department is located at the university campus and is
equipped with the necessary analytical equipment. Additionally the basic laboratory equipment, molecular
biology and cell culture equipment is also located in the department. The Department is part of the
Institute of Biological Chemistry and Nutritional Sciences within the Faculty of Natural Sciences. Within the
institute, faculty and university additional resources can be used.
Profile of the group: The work of the team is focussed on the measurement of oxidative stress related
changes in cellular metabolism. Age-related changes of oxidative stress and antioxidative defences during
normal aging and in age-related, neurodegenerative diseases are key problems being addressed. Special
attention is given to the oxidative damage of proteins and the removal of oxidized proteins from the cellular
systems. Besides protein oxidation several questions on lipid peroxidation processes are being
addressed. To fulfil such a task a number of methods are routinely used and standardized for the analysis
of human samples. A number of these analytical studies were already used in human studies, including an
aging study.
Some important recent findings of the team in the field of oxidative stress, protein oxidation and protein
degradation are the following: (i) the role of the proteasome in the removal of oxidized proteins; (ii) the
inhibition of the proteasome by oxidized, cross-linked protein aggregates and lipofuscin, (iii) the activation
of the nuclear proteasome by poly-ADP-ribose polymerase, and (iv) the decline of proteasome and the
increase in protein oxidation during in vitro senescence of proliferating and non-proliferating cells. To test
whether this is also related to real in vivo changes we measured (i) the inhibition of the proteasome in
Alzheimer’s disease affected brain samples; (ii) the increase of protein oxidation and other oxidation
products in a limited cohort during the aging process; and (iii) the UVA induced damage of human skin.

WP6: Oxidative stress markers Clinical chemistry, hormones and markers of metabolism

WP9: Dissemination and training

WP10: Project management and ethical issues

Martin-Luther Universität Halle-Wittenberg

PD Dr. Andreas Simm

The Department of Cardiothoracic Surgery at MLU Halle-Wittenberg was among the first in Germany to
become committed to experimental gerontology. Furthermore the University’s Medical Faculty was the first
in Germany to establish an integrated research program of the “Deutsche Forschungsgemeinschaft”
(German Research Foundation; DFG) in the field of gerontology.
Dr. Andreas Simm holds the position of a “Hochschuldozent” (Associate Professor) and is Chairman of
Section I (Experimental Gerontology) of the German Society of Gerontology and Geriatrics. He is the
leader of the research units of the Department of Cardiothoracic Surgery and of the Centre of Basic
Medical Science of the Medical Faculty, LMU Halle. He is also head of a genomic core facility, specifically
for microarray analysis.
His laboratory is equipped with standard biochemical, molecular biology and cell culture equipment as well
as with an affymetric microarray facility. The major interests of Dr. Simm’s group are age-dependent tissue
changes leading to diseases (cardiovascular aging, lung cancer development, regeneration by stem cells).
The underlying major molecular mechanism investigated, which is apparently common to the above
conditions, is sugar dependent modifications of proteins, the age and diabetes dependent advanced
glycation end products (AGEs). Current studies are focused on investigation of the changes in micro-RNA
(miRNA) pattern during aging of cardiac tissue in rats.
Project manager is Dr. rer. nat. Andreas Simm. He is responsible for the planning and supervision of all
studies performed by Beneficiary 20. Dr. Vesselin Christoph (PhD) is responsible for the miRNA chip
analysis. Dr. Christoph is a molecular biologist and since 5 years responsible for the microarray core unit
of the medical faculty of the Martin-Luther University Halle Wittenberg. Dr. Norbert Nass, a biochemist, is
experienced in protein analytics. He will give advice for the biochemical and fluorescence analytic of AGEs
in the plasma.
In MARK-AGE, Dr Simm’s group will analyse Advanced Glycation Endproducts in plasma (WP3) as well
as the miRNA expression patterns in the cells harvested from defined ageing cohorts (WP7).

WP3: Markers based on proteins and their modifications

WP7: Emergent biomarkers of ageing from model systems and novel methodological approaches

WP9: Dissemination and training

WP10: Project management and ethical issues

UNIBO

ALMA MATER STUDIORUM UNIVERSITÁ DI BOLOGNA

Prof. Claudio Franceschi

The Interdepartmental Centre “L. Galvani” (CIG) at the University of Bologna includes 10 Departments
and 39 researchers of different disciplines whose main aim is to study with a multidisciplinary
approach the problem of complexity. One of the main interests of CIG is the study of human aging and
longevity. Within the CIG, Prof. Franceschi has a fully equipped laboratory of 400 m 2 ..
Main tasks in the project
Beneficiary 21 has accumulated a large experience in the recruitment of very old people for several
national and European projects, and particularly as Coordinator of the GEHA Project. Furthermore, the
group acquired substantial experience in mtDNA sequencing and published several papers on the
cross-talk between nuclear and mitochondrial genome, as well as on the role of mtDNA in human
aging and longevity or age-associated diseases such as AD. Beneficiary 21 will test the reliability of
mtDNA somatic mutations at the mtDNA control region as a biomarker for successful aging. Finally,
using a MassARRAY EpiTYPER, a mass spectrometer (MALDI-TOF) specifically designed for DNA
analysis (SEQUENOM®), Beneficiary 21 will detect DNA methylation status of the chromosomal
region 11p15.5 in subjects recruited within MARK-AGE, in collaboration with Beneficiary 23.
Principal Investigator: Previous experience relevant to those tasks.
Claudio Franceschi is Full Professor of Immunology. He is the founder and former Director of the CIG
and former Scientific Director of the Italian National Research Center on Aging (INRCA). He is the
Coordinator of the FP6 IP “GEHA – Genetics of Healthy Aging”. Prof. Franceschi, together with Prof.
Daniela Monti pioneered the field of biology of human longevity by proposing the experimental model
of centenarians as well as many theoretical models for aging and longevity. He is author of more than
450 papers in peer-reviewed international journals. Stefano Salvioli contributed to the studies on the
involvement of mitochondria and of p53 polymorphisms in apoptosis. Miriam Capri contributed to the
studies on human immunosenescence. Gastone Castellani is a researcher in physics with a great
experience in systems biology and the analysis of complex data.

WP1: Recruitment of probands and physiological markers

WP2: DNA-based markers

WP8: Data analysis and bioinformatics

WP9: Dissemination and training

WP10: Project management and ethical issues

Unilever UK Central Resources Limited

Dr. Jonathan Powell

Unilever’s strategic Corporate Research Group is responsible for the Company’s long-term physical and
engineering science and bioscience research programmes. Specifically this group is charged with the
identification of emerging new science and technology which could deliver to growth of current businesses
and the establishment of new business opportunities. The group is interdisciplinary in nature being comprised
of mathematicians, psychologists, IT experts, chemists, nutritionists, physiologists and a range of bioscience
expertises. The Bioscience Group has access to modern cell and molecular biology facilities, including 6-MHz
NMR, GC-MS and gene and protein array platforms. The site has Marie-Curie training status and sponsors a
large number of national PhD studentships as well as collaborating in several EU FP5 and FP6 projects
(NOE ImAginE, IPs: T-CIA, UV-Biomarkers, ISOHEART, PHYTOS, ZINCAGE,-EXGENESIS).
The fifty strong Bioscience group has a long standing experience of ageing biology, particularly the
interactions between oxidative, neuroendocrine and inflammatory stressors and their metabolic sequelae
that lead to poor ageing trajectories. The group has championed an integrated a holistic view of ageing,
where dysregulated, maladaptive, chronic stress responses lie at the heart of metabolic disturbances. The
group works at the organism, gene, protein and metabonome levels.

WP5: Clinical chemistry, hormones and markers of metabolism

WP6: Oxidative stress markers Clinical chemistry, hormones and markers of metabolism

WP8: Data analysis and bioinformatics

WP10: Project management and ethical issues

 

Université degli Studi di Roma “La Sapienza”

Prof. Paola Caiafa

Paola Caiafa is Full Professor of Clinical Biochemistry and Clinical Molecular Biology at the II Faculty of
Medicine, University of Rome “La Sapienza”. She is leader of a research group working in the
Department of Cellular Biotechnologies and Haematology. The Department comprises internationally
renowned researchers. Paola Caiafa has been working on the topic “DNA methylation in chromatin
structure” for many years. Her aim is to identify the mechanism involved in maintaining the
unmethylated state of “CpG islands” and how these DNA regions, which remain protected from
methylation in normal cells, are susceptible to methylation in tumour cells. Her research group has
found a correlation in vivo between poly(ADP-ribose) polymerases (PARPs) and DNA methylation. In
fact, PARPs are involved in controlling the methylation pattern which characterizes genomic DNA in
eukaryotic cells and two models have been suggested to explain the cross-talk between DNA
methylation and poly(ADP-ribosyl)ation.

WP2: DNA-based markers

WP9: Dissemination and training

WP10: Project management and ethical issues

Université Pierre et Marie Curie – Paris 6

Prof. Bertrand Friguet

The University Pierre et Marie Curie – Paris 6 is the leading French University in Medicine and Sciences
that offers under-graduate, post-graduate and post-doctoral training in Life Sciences. Prof Friguet heads
the Master programme on ‘Biology of Ageing’ and he is co-director of the Doctoral School ‘Biochemistry
and Molecular Biology’ (B2M) which offers a variety of teaching units and workshops that are open to PhD
students and post-doctoral fellows. The laboratory disposes of biochemical, molecular biology and cell
culture equipment, including protein purification and proteomic evaluation using 2D gel electrophoresis.
The major focus of Prof Friguet’s team is the oxidative and related modifications of proteins and
maintenance systems in ageing and oxidative stress-related pathologies. Proteins are indeed the target of
such post-translational modifications as oxidation, glycation, conjugation with lipid peroxidation products,
which increase with age and affect their biological function. Important recent findings of the team include
(1) the demonstration that damaged protein accumulation is associated with a decline in proteasome
activity in cellular ageing as well as in certain pathological situations such as cardiac ischaemia-
reperfusion or UV stress; (2) the characterization of damaged proteins that escape degradation by the
proteasome; (3) the creation of a panel of antibodies directed against specific protein modifications that
can be used as bio-markers of ageing and that have been applied to probe the age-related modification
status of proteasome as well as of cytosolic protein patterns; (4) the implication in protection against
oxidative stress and in redox modulation of protein interactions of the peptide methionine sulphoxide
reductase, an ubiquitous enzyme that reduces oxidized methionine within proteins and exhibits a
decreased expression and activity upon ageing, and (5) the characterization of age-related loss of function
of the Lon protease and its role in oxidatively modified mitochondrial proteins accumulation with age.
Prof Bertrand Friguet is Head of the Laboratory of Cellular Biochemistry and Biology of Ageing in the
Biology Department of University of Paris 7 located at the Jussieu Campus. The Laboratory of Cellular
Biochemistry and Biology of Ageing was created in 1997 on the theme “Post translational modifications of
proteins and maintenance systems in ageing”. The laboratory has been funded by the French Ministry of
Research from the beginning, has been renewed in 2001 and 2005 for four years in 2005.
Prof Friguet has been a Visiting Associate in 1993-94 in Dr. Earl Stadtman’s laboratory at the NIH and a
junior member at the ‘Institut Universitaire de France’ from 1995 to 2000. He was promoted by the
Biochemistry Department to Associate Professor in 1998. In 2007 he was appointed as Full Professor at
the Physiology Department of the University Pierre et Marie Curie – Paris 6 (UPMC) for setting up a new
research unit on aging, nutrition and inflammation. In FP5, he has been the co-ordinator of the shared cost
action ‘ProtAge’. In FP6, he was a partner in the STREP ‘Zincage’ and is currently work package leader of
the IP Proteomage. Prof Friguet is member of the Editorial Board of Biogerontology.

WP3: Markers based on proteins and their modifications

WP9: Dissemination and training

WP10: Project management and ethical issues

Academisch Ziekennhuis Leiden – Leids Universitair Medisch Centrum

Prof. P. Slagboom

The Leiden University Medical Center (LUMC) is an organization of 8,000 employees, merged its activities
with the Leiden University. LUMC is committed to improvement of health care quality by performing its
core activities, i.e. patient care, research, education, training of medical specialists and postgraduate
education. Research at LUMC is highly renowned at the international level, and esearch into human
ageing and longevity is among the top priorities. Research of longevity and age-related diseases is
especially performed in collaborations of the Gerontology and Molecular Epidemiology sections headed by
Professos Westendorp and Slagboom, respectively, involving 50 scientific staff and technicians.
Eline Slagboom, PhD is Full Professor and Chair of Molecular Epidemiology at the LUMC Dept of
Medical Statistics and Bioinformatics. Rudi Westendorp, MD is Full Professor and Chair of the Geriatrics
and Gerontology Department of the LUMC. In the past twenty years, ageing research by these groups has
been performed in population based studies of subjects over 85 years (Leiden 85 plus Study), which has
resulted in numerous publications on phenotypic and genetic markers of longevity. Studies into age-
related diseases are focused on patient based cohort studies for cardiovascular disease, cognitive
impairment and osteoarthritis. A new study cohort for the identification of genetic and biomarkers of
human longevity was established over the past 7 years comprising 450 nonagenarian siblings from
families with survival advantages extending over several generations (4). This study also includes the
offspring of the long-lived siblings and spouses of the offspring and was designed in such a way as to
enable genetic studies in different approaches and to integrat them with explorative and candidate
biomarker studies. Also a follow up study (of the offspring) is being planned to become a basic platform for
epidemiological studies into ageing/longevity. The full study population is now being thoroughly analysed
for potential biomarkers at multiple levels of -omics research. Genome wide association and linkage scans
have been performed, RNA expression profiles are being generated as well as genome wide and locus
specific DNA methylation analyses (1), metabolomics (2) and proteomics profiles are being generated and
classical parameters (3) are being investigated for their value as prospective markers of human health.
The genetic studies are embedded in the Centre for Genotyping headed by the Slagboom Group currently
actively handling 50,000 DNA samples for genotyping from studies of different universities for the
exploration of genetic influences in many age-related conditions. The ultimate goal of the combined efforts
of Profs Slagboom and Westendorp is to collect and integrate data at different molecular and clinical levels
to understand the pathways of healthy ageing and protection from disease (progression).

WP1: Recruitment of probands and physiological markers

WP5: Clinical chemistry, hormones and markers of metabolism

WP9: Dissemination and training

WP10: Project management and ethical issues

University of Tampere

Dr. Antti Lauri Juhani Hervonen

Since 1995 a multidisciplinary team of around 20 scientists at the University of Tampere has been co-
ordinated by Prof Hervonen around the topic of exeptional longevity, within the ‘Vitality 90+’ project.
Consecutive cohorts of nonagenarians in the city of Tampere and surrounding area were chosen as target
population. Interviews, clinical studies as well as assessment of functional capacities have been
performed regularly. Biological samples were collected for the first time in 1997. The genetic studies
focused on cytokine gene polymorphisms, cardiovascular risk genes and mtDNA haplotypes. Each cohort
has been followed up to 4-5 years and mortality data are available. To date, about 3,200 nonagenarians
have been studied in the framework of the ‘Vitality 90+’ project.
In 2003 the team was invited to join the GEHA consortium, an FP6 IP coordinated by Prof Franceschi. The
responsibility of the Tampere team as a partner within the GEHA project was to recruit 180 “trios”. A
recruitment organization was established in 2004 and is still available. The goal was reached by the end of
2006. The process of tracing the offspring and further generations of the GEHA subjects was already
started in early 2007.
Within the MARK-AGE project the group will contribute to the recruitment of sons and daughters of Finnish
GEHA subjects, and their spouses (WP1) and to the analysis of systemic inflammation markers (WP5).

WP1: Recruitment of probands and physiological markers

WP5: Clinical chemistry, hormones and markers of metabolism

WP10: Project management and ethical issues