European researchers define research priorities in biogerontology

The quality of the medical care for geriatric patients is a major investment for society and must imperatively be a research priority in Europe. This is why 50 European researchers, met on May 17 - 19 in Brussels, to define the research priorities in the field of biogerontology for the next 10 to 15 years. They presented their conclusions during a press conference on Wednesday May 19 2010.

The ambition of biogerontology is to give as great a number of people as possible the opportunity to live out their old age in good health by delaying dependency and the onset of aged-related diseases: brain degeneration, diabetes, osteoporosis, cardiovascular diseases, alteration of the vision, the decline of the immune functions, muscular atrophy or the frailty of the skin.

Several laboratories in Europe are researching the subject, often through organisation into consortia. Important scientific achievements have been obtained these last ten years, as shown by the 2009 Nobel prize in Physiology attributed to researchers that explained the molecular mechanism of telomeres shortening (the extremities of the chromosomes), one of the factors involved in the cellular ageing. Research has also identified several components of the ageing phenomenon as oxidative stress, mitochondria functioning, mutation accumulation into the genome…

A crucial step to reinforce the constructive results arising from previous Framework Programmes in the Biogerontology area is to establish a road map for European research on the molecular aspects of healthy human ageing.

This initiative is in keeping with the European project WHYWEAGE coordinated by the research unit in cellular biology from the university of Namur.

The objectives of the project were to identify emerging fields of interest for molecular gerontology, which could allow great scientific achievements, and applications of socio-economic interest and to inform the Commission, the health care providers, the industry and the public via the production of a policy document entitled ' a road map for molecular gerontology research in Europe'.

To achieve these objectives, WHYWEAGE supported of a coordinated series of research workshops on identified topics terminating in an integrative conference. Each workshop was open to a maximum of 20 attendees allowing extensive and intensive discussions on the future of the discipline.

This series of workshops has been concluded by an integrative conference during which the final document has been discussed, written and presented in its major outlines to the scientific officer from the European Commission in charge of the research projects on ageing biology. 160 scientists (including 44 women et 116 men) from 21 European countries have attended at least one thematic workshop.

Around 40 delegates from the 10 different thematic workshops have met in Brussels on May 17 and 18 to prepare the document.

The major outlines that came out of the work are the following:

• Target nuclear receptors involved in aged-related diseases (principally neurodegenerative and metabolic diseases) ;
• Develop systems biology (modelisation) in the frame of ageing ;
• Define recommendations in terms of nutrition ;
• Find solutions to preserve the strength and the mass of the muscles ;
• Better understand the deterioration of the immune system ;
• Maintain the efficiency of cellular repair systems ;
• Identify biomarkers that allow to define the biological age and the outset of aged-related diseases ;
• Further study vascular ageing ;
• Better understand the basic mechanisms of ageing : telomeres shortening, genome and mitochondria damages, cellular senescence ;
• Increase the research potential for research on skin ageing, from basic science to clinical research ;
• Use molecular biology in geriatric studies (Frailty predictive markers)

Thematic

Biomarkers on ageing and longevity

Reliable assessment of the state of ageing of a living individual is currently not possible. A strategy to solve this problem is the identification of (an) age-related change(s) in body function or composition that could serve as a measure of "biological" age and predict the future onset of age-related diseases and/or residual lifetime more accurately than chronological age does. Such parameters are termed "biomarkers of ageing". 

Systems biology and its applications to biological ageing.

Systems biology is necessary to make progress in understanding the underlying biology at a level that finally allows the design of safe but powerful approaches to interventions that aim at extending healthy lifespan. The importance of individual tools and approaches is dependent on experimental design, biological objectives, and data, which means that systems biology expertise is needed in every step in ageing research: starting from experimental design and ending to result interpretation, documentation and dissemination.  Systems biology can also bring in methods from fields outside biology, such as reliability theory, that might be useful in ageing research.

Oxidative stress, protein damage and maintenance         

Protein damage combined with an age-dependent decline in anti-oxidative capacity and protein quality control result in an imbalance of protein homeostasis, that has been clearly linked to ageing. Indeed, oxidized protein accumulation is a hallmark of cellular aging while protein aggregates formation has been also implicated in the pathogenesis of age-associated degenerative diseases.

Telomeres, DNA damage, mitochondria and senescence

Telomere shortening, nuclear and mitochondrial DNA damage and repair, mitochondrial dysfunction and cell senescence are basic mechanisms that synergistically contribute to ageing. Importantly, these processes are tightly interlinked by multiple signalling networks and response pathways. Recent research suggests these as potent candidate targets for interventions aimed at extending healthy lifespan in model organisms including mammals and, ultimately, humans.

Targeting nuclear receptors in age-related diseases (particularly neurodegenerative disease and metabolic disease)

Nuclear receptors (NRs) organise and modulate physiological responses. Their ligand-gated transcriptional control coordinates environmental and nutrient signals with metabolism, development, reproduction, homeostasis, and thereby aging. NRs have a long evolutionary history,  thereby contributing to their complexity of action. They are prime drug targets but increased knowledge is required of their specificities and cross-talk in different aspects of aging.

Vascular Ageing

Ageing is the major risk factor for cardiovascular disease, nowadays the most important public health problem in the ageing European population. Vascular ageing is a phenomenon where biology, lifestyle and social factors converge to accelerate a pathophysiological process resulting in both subclinical and clinical events, ranging from cognitive decline to heart failure and stroke. Current therapeutic interventions do not tackle the manifestations of vascular disease specifically related to the underlying organismal ageing. To address this situation there is an urgent need to gain a detailed understanding of the complex interactions between the molecular, biochemical, morphological and functional aspects of vascular ageing.

Immunosenescence and inflammation

Dysregulated or compromised immunity ("immunosenescence") in older adults results in their decreased control of infectious disease, poorer response to vaccination, and increased signs of systemic inflammation ("inflammaging") contributing to age-related diseases like diabetes, dementia and heart attacks. These diseases represent the biggest public health burden in our ageing population; overcoming immunosenescence is thus a topic of crucial importance.

Metabolism and Ageing

Recent advances in biogerontology are increasingly pointing to the central importance of metabolism as a determinant of ageing and health. Studies of metabolism, how it changes with age, and how interventions can slow ageing and increase healthy lifespan have the potential both to provide a deeper understanding of the biology of ageing and to improve late life health. In particular, a combination of recommendations in terms of lifestyle and nutrition, with appropriate drugs can be a powerful means of promote healthy ageing.

Sarcopenia, muscle weakness and physcial activity

Preservation of muscle mass and strength are now recognised as prerequisites for healthy ageing. Amongst the elderly population, 42% of males and 57% of women aged 70-79 suffer from sarcopenia. Age-associated loss of neuromuscular integrity, reduced regenerative capacity, inflammation and anabolic resistance have a major impact on muscle function and physiological reserves. Adoption of an inactive lifestyle and poor nutrition further exacerbates sarcopenia. Sarcopenia is becoming increasingly compounded by intramuscular fat accumulation due to increased prevalence of obesity in the older population. This results in sarcopenic obesity leading to further loss of muscle mass and mobility and serious additional health risks, such as metabolic syndrome. 

Skin ageing and elastic tissues, biotechnologies in biogerontology

Skin is the functional barrier, between outside and inside of the body, preventing water loss, UV protection, the entry of adverse environmental agents and microbes. Skin is ageing, which results in impaired functional barrier, accumulation of defects  under the daily insults and impair repair. As a results of skin ageing, the incidence of non melanoma skin cancer (NMSC) and chronic wounds increase, while the defense mechanisms and functional barrier decreases (dermatoporosis).

Clinical biogerontological studies

The workshop on Clinical Biogerontological research was aimed to fill the gap between the clinician's views and the biogerontologists projects for the research on aging. This meeting was important because it allowed to define a common vision in ageing research and to strengthen the mutual contributions to innovative projects. It allowed in addition to address the means to encompass the obstacles regarding ethical regulations, patient's characterization and follow-up.