Pascal Sommer

European silver paper on the future of health promotion and preventive actions, basic research and clinical aspects of age related disease

Background. In September 2008, under the French Presidency of the European Union and with the support of the Polish Minister of Health, a European Summit on Age-Related Disease was organised in Wroclaw (Poland). At this meeting, European politicians, gerontologists and geriatricians gathered to discuss a common approach to future challenges related to age-related disease. Politicians and decision-makers from the European Union and Ministers of Health and their deputies from many European countries raised the problems and difficulties to be tackled in a growing population with a high burden of disease, and asked scientists to write a consensus document with recommendations for future actions and decisions. Scientists and clinicians worked in parallel in three different groups, on health promotion and preventive actions, basic research in age-related disease, and clinical aspects of disease in older people. Beforehand, the format of the paper with recommendations was discussed, and it was finally agreed that, for a better understanding by decision-makers, it would be divided in two different columns: one with facts that were considered settled and agreed by most experts (under the heading We know), and a second with recommendations related to each fact (We recommend). No limit on the number of topics to be discussed was settled. After careful and detailed discussion in each group, which in most cases included the exact wording of each statement, chairpersons presented the results in a plenary session, and new input from all participants was received, until each of the statements and recommendations were accepted by a large majority. Areas with no consensus were excluded from the document. Immediately after the Summit, the chairpersons sent the document both to the main authors and to a list of experts (see footnote) who had made presentations at the summit and agreed to review and critically comment on the final document, which is presented below. As regards the scientific aspects of the planning of the Summit, several organisations, under the leadership of the EUGMS, were asked both to review the program and to suggest names of speakers and participants. After the Summit, the Boards of these organizations (European Union Geriatric Medicine Society (EUGMS), International Association of Gerontology and Geriatrics-European Region (IAGG-ER), European Association of Geriatric Psychiatry (EAGP), International Society of Gerontechnology (ISG) and International Society for the Study of the Aging Male (IS-SAM) agreed to consider the document as an official paper, and help with its dissemination. The name Silver Paper was used, recalling the grey or silvery hair of our older citizens, as an easy reference. It has been sent officially to several bodies of the European Union and to Health Ministers of most European countries; and will be published in other languages in local purnals. Its declared intention is to foster changes in policies which may, in the future, reduce the burden of disease in old age.

Silver paper: the future of health promotion and preventive actions, basic research, and clinical aspects of age-related disease--a report of the European Summit on Age-Related Disease.

Background. In September 2008, under the French Presidency of the European Union and with the support of the Polish Minister of Health, a European Summit on Age-Related Disease was organised in Wroclaw (Poland). At this meeting, European politicians, gerontologists and geriatricians gathered to discuss a common approach to future challenges related to age-related disease. Politicians and decision-makers from the European Union and Ministers of Health and their deputies from many European countries raised the problems and difficulties to be tackled in a growing population with a high burden of disease, and asked scientists to write a consensus document with recommendations for future actions and decisions. Scientists and clinicians worked in parallel in three different groups, on health promotion and preventive actions, basic research in age-related disease, and clinical aspects of disease in older people. Beforehand, the format of the paper with recommendations was discussed, and it was finally agreed that, for a better understanding by decision-makers, it would be divided in two different columns: one with facts that were considered settled and agreed by most experts (under the heading We know), and a second with recommendations related to each fact (We recommend). No limit on the number of topics to be discussed was settled. After careful and detailed discussion in each group, which in most cases included the exact wording of each statement, chairpersons presented the results in a plenary session, and new input from all participants was received, until each of the statements and recommendations were accepted by a large majority. Areas with no consensus were excluded from the document. Immediately after the Summit, the chairpersons sent the document both to the main authors and to a list of experts (see footnote) who had made presentations at the summit and agreed to review and critically comment on the final document, which is presented below. As regards the scientific aspects of the planning of the Summit, several organisations, under the leadership of the EUGMS, were asked both to review the program and to suggest names of speakers and participants. After the Summit, the Boards of these organizations (European Union Geriatric Medicine Society (EUGMS), International Association of Gerontology and Geriatrics-European Region (IAGG-ER), European Association of Geriatric Psychiatry (EAGP), International Society of Gerontechnology (ISG) and International Society for the Study of the Aging Male (IS-SAM) agreed to consider the document as an official paper, and help with its dissemination. The name Silver Paper was used, recalling the grey or silvery hair of our older citizens, as an easy reference. It has been sent officially to several bodies of the European Union and to Health Ministers of most European countries; and will be published in other languages in local purnals. Its declared intention is to foster changes in policies which may, in the future, reduce the burden of disease in old age.

Differential Expression of Lysyl Oxidases LOXL1 and LOX During Growth and Aging Suggests Specific Roles in Elastin and Collagen Fiber Remodeling in Rat Aorta

The extracellular matrix (ECM) plays an important role in vascular tissue structure, maintenance, and function. Lysyl oxidases catalyze a key step in the posttranslational cross-linking of elastin and collagens in the ECM. Gene knockout studies in mice suggested a role for lysyl oxidase-like (LOXL1) in adult elastin synthesis and a role for its isoform, lysyl oxidase (LOX), in the synthesis of both collagens and elastin during development. However, the relative expression of both isoforms as a function of age is not known and was therefore investigated here. LOX and LOXL1 immunohistochemistry and real-time RT-PCR were performed during development, growth and aging in the aorta of LOU and Brown-Norway (BN) rats, two inbred strains with different susceptibilities to arterial fragility. In addition, expression of genes encoding for elastic fiber proteins and type I collagen, together with elastin and collagen contents, was measured in adult and old rat aortas. High aortic LOX expression was observed early in the development (embryonic day 15), followed by a drastic reduction in adulthood, whereas LOXL1 was mainly detectable in the intima and media; its expression was maintained throughout life in the LOU rat. Expression of tropoelastin, type-I collagen, and LOXL1 genes was reduced in the aorta of 6-week-old BN rats. Aging is characterized by a decreased elastin/collagen ratio and a greatly decreased expression of LOX, tropoelastin, and type-I collagen. These findings indicate a different spatial and temporal expression of LOX and LOXL1 during growth and aging in the rat aorta and suggest specific roles for LOX and LOXL1 in the synthesis and remodeling of elastic and collagen fibers.

Comparison of ex vivo and in vitro human fibroblast ageing models.

Several studies have analyzed modulation of gene expression during physiological ageing with interesting, but often contradictory results, depending on the model used. In the present report we compare age-related metabolic and synthetic parameters in human dermal fibroblasts (HDF) isolated from young and old subjects (ex vivo ageing model) and cultured from early up to late cumulative population doublings (CPD) (in vitro ageing model) in order to distinguish changes induced in vivo by the aged environment and maintained in vitro, from those associated with cell senescence and progressive CPD. Results demonstrate that fibroblasts from aged donors, already at early CPD, exhibit an impaired redox balance, highlighting the importance of this parameter during ageing, even in the presence of standard environmental conditions, which are considered optimal for cell growth. By contrast, several proteins, as those related to heat shock response, or involved in endoplasmic reticulum and membrane trafficking, appeared differentially expressed only during in vitro ageing, suggesting that, at high CPD, the whole cell machinery becomes permanently altered. Finally, given the importance of the elastic component for a long-lasting connective tissue structural and functional compliance, this study focuses also on elastin and fibulin-5 synthesis and deposition, demonstrating a close relationship between fibulin-5 and ageing.

European silver paper on the future of health promotion and preventive actions, basic research, and clinical aspects of age-related disease

The current article is a statement of the meeting with international and multidisciplinary participation, held in Wrocław, Poland on September 11–13, 2008. The meeting was devoted to working out a position focusing on the challenge for individuals, health care systems, biological, psychosocial, epidemiological, medical, and public health sciences in the ageing populations of the twenty-first century. The statement is presented as an overview, in tabular format, of the current European situation regarding basic biological research on ageing, health promotion and preventive action, clinical care for older people, and recommendations for future actions. (Pol J Endocrinol 2009; 60 (5): 408–414)

European Silver Paper. Documento europeo sobre el futuro de la promoción de la salud y las acciones preventivas, la investigación básica y los aspectos clínicos de las enfermedades relacionadas con el envejecimiento

El envejecimiento de la población es uno de los mayores logros de la humanidad y Europa está a la cabeza de esta historia de éxitos. Sin embargo, el envejecimiento y las enfermedades relacionadas con la edad suponen también un desafı́o creciente para las personas, para los sistemas de asistencia sanitaria y para las ciencias de salud pública, biológicas, psicosociales, epidemiológicas y médicas. Muchos cientı́ficos de todas las áreas cientı́ficas y del conocimiento mencionadas trabajan activamente para entender mejor el envejecimiento y hacer frente a los retos que este fenómeno plantea a los individuos del siglo XXI. No se pueden afrontar estos retos desde un punto de vista único. Para enfrentarse a ellos es necesario un frente unido, activo y coordinado de muchas disciplinas, y también una estrategia que, partiendo de la investigación básica, alcance todos los aspectos del envejecimiento. Esto supone que la investigación traslacional es un requisito esencial y que los avances que surjan de la investigación deberı́an fluir rápidamente, a través de la formación de los profesionales, hasta influir en la promoción de estilos de vida saludables, para permitir que la asistencia sanitaria y social resuelvan las necesidades de las personas mayores. Se deben adoptar estrategias durante todo el ciclo vital, basadas en la evidencia, adaptadas en su caso a las personas mayores, que

Insulin–transferrin–selenium as an alternative to foetal serum for epidermal equivalents

Organotypic skin models are powerful tools for research in development, ageing and diseases. They have become more and more complex with the use of multiple cell types. This requires a culture medium adapted to optimize the development of such in vitro skin. Foetal bovine serum (FBS) is the most complete supplement in existence at the moment, providing at once growth factors, vitamins, hormones and other circulating compounds. However, this cocktail suffers from batch variability and its animal origin is ethically questionable. More importantly, its biological activities may interfere with the study of certain signalling pathways. Here, we present a strategy for constructing an epidermal equivalent using a defined culture medium without serum.

Heparan Sulfate Affects Elastin Deposition in Fibroblasts Cultured from Donors of Different Ages

Heparan sulfate (HS), due to its presence on the cell surface and in the extracellular milieu and its ability to modulate cell signaling, has a fundamental role in both physiological and pathological conditions. For decades we have demonstrated the occurrence of interactions between glycosaminoglycans (GAGs) and elastic fibers. In particular, we have recently shown that HS is present inside elastic fibers and plays a role in the assembly and stability of elastin coacervates. Elastin represents, within the extracellular matrix, the component most severely affected during aging, and changes in the synthesis and posttranslational modifications of HS have been described, possibly influencing cellular behavior and protein interactions. Thus, the present study has investigated, in two different in vitro experimental models, the role of HS on elastin deposition and assembly. Results demonstrate that: (1) Biological effects of HS are partly dependent on the physicochemical characteristics of the GAGs; (2) HS does not affect attachment, viability, and growth of human dermal fibroblasts; (3) HS does not modify elastin gene expression nor elastin synthesis, but favors α-elastin aggregation and, independently from the age of donors, elastin assembly; (4) HS significantly increases the expression of fibulin 5, and these effects are especially evident in fibroblasts isolated from aging donors. These data provide a better understanding of the biological role of HS and offer new perspectives regarding the possibility of restoring and/or preserving the elastic component with aging.

In vitro epidermis model mimicking IGF-1-specific age-related decline

Ageing is a complex multifaceted process affecting skin functionality and structure. Several 3D organotypic skin culture models have reproduced ageing by inducing replicative senescence, glycation or oxidative stress. Yet, very few models have focused on hormonal ageing and especially the insulin‐like growth factor 1 (IGF‐1) signalling pathway, which has been associated with longevity in animal studies and is necessary for the early stages of skin development. In this study, we built an organotypic epidermis model with targeted IGF‐1 receptor knockdown to reproduce some aspects of hormonal ageing on skin. Our model displayed morphological and functional features of aged epidermis, which were mostly attributed to a loss of function of the Stratum basale. IGF‐1 receptor knockdown keratinocytes depicted an extended cell cycle, reduced proliferation potential and reduced adhesion capacities and greater sensitivity to oxidative stress than control cells. Altogether, this model represents an essential tool for further investigations into the mechanisms linked to some aspects of hormonal decline or when screening for potent anti‐ageing compounds.