CODEAGE

The role of Chronic DNA damage in Ageing and Age-related pathology

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 Obiettivo del progetto (Objective)

'Ageing is an inexorable homeostatic failure of largely unknown aetiology that leads to increased vulnerability to disease limiting the quality of life in the elderly and creating high costs to the society. Until recently, the daunting complexity of the ageing process, the conspicuous lack of tools to study it, and a dearth of experimentally tractable model systems have greatly hindered any hypothesis-driven reductionist approaches to understand the molecular basis of ageing. Whereas molecular and cellular damage is thought to be a cause of ageing and age-related pathologies, little is known about the molecular events that underlie ageing or determine longevity. A large number of progeroid syndromes that are characterized by an early onset of age-related pathology are linked to inborn defects in genome maintenance thus pointing towards damage in (nuclear) DNA as a major culprit of ageing and age-related pathology. DNA damage fuelled by intrinsic and environmental sources of genotoxic insult and by errors of genome maintenance mechanisms invariably accumulates with advancing age. The outcome of DNA damage is diverse and generally adverse: DNA lesions may physically obstruct essential processes including DNA replication and transcription. In addition, DNA damage activates checkpoint responses that lead to a reduction in cell proliferation potential (cellular senescence) or to an increase in cell death. As a result, depending on the type and severity of DNA injuries and the cellular response to DNA damage, these cellular mechanisms impair organ maintenance and function during ageing. The CodAge ITN proposes an integrated approach in studying the role of Chronic DNA damage in Ageing and age-related pathology.'

Introduzione (Teaser)

Increase in longevity brings with it age-associated decline in organ function and increased disease risk. EU funded researchers are working on elucidating the genetic mechanisms that could facilitate healthy ageing.

Descrizione progetto (Article)

Ageing is associated with debilitating diseases such as osteoporosis, cardiovascular disease, cognitive impairment, diabetes and cancer. In countries with a growing proportion of elderly people such as in Europe, this has serious socioeconomic consequences.

Research implicates damaged DNA as driving force of ageing and age-related pathology. Both intrinsic and environmental insults constantly attack the genome leading to accumulation of DNA damage with advancing age that causes a host of pathologies.

The EU-funded http://www.itn-codeage.eu (CODEAGE) (The role of chronic DNA damage in ageing and age-related pathology) project is an initial training network determined to gain insight into the underlying molecular mechanisms of ageing. This network brings together young researchers and leading experts from academia and research institutes as well as small and medium sized enterprises.

During the first project phase, CODEAGE recruited thirteen early-stage and one experienced researchers. These researchers are employing cutting-edge technologies to study different genetic model systems such as Saccharomyces cerevisiae, Caenorhabditis elegans, Mus musculus and human cells. Already, significant research outcomes have been published in several papers in PubMed.

During meetings organised by CODEAGE, project researchers gave oral presentations and networked with participating businesses. Besides sharing scientific progress and experiences, they updated the CODEAGE career development plan for each researcher.

In addition to local courses and weekly lab meetings, training activities included language courses, journal clubs, summer schools, international conferences and training workshops.

Research outcomes will provide the foundation for developing effective strategies to prevent or delay age-related pathologies. Project findings will identify biomarkers that will prove useful for developing better drugs and monitoring treatment efficacy. This should improve the quality of life of the elderly population while reducing age-associated healthcare expenses, thus relieving the drain on the economy.