PROPAG-AGEING

The project

PROPAG-AGEING

In the last decade, life expectancy in Europe increased by 2.9 years, reaching 80.6 years in 2013. However, living longer does not necessarily mean living better. With increasing age comes increased likelihood of chronic diseases, which affect the wellbeing of the elderly and pose an increasing social and economic burden on Europe. Among these, Parkinson’s disease (PD) is the second most frequent common neurodegenerative pathology after Alzheimer’s disease and the first motor neurodegenerative disorder.
Despite the evidence that age is a major risk factor for PD, the relationship between the molecular alterations of healthy ageing and those underpinning PD pathogenesis are unclear.

PROPAG-AGEING hypothesis is that the environment feeding PD onset and progression is the elderly physiology, and that there is a continuum between healthy ageing and neurodegenerative motor disorders. The project is based on the most advanced conceptualization of the ageing process and PD, and adopts an unifying propagation/transmission hypothesis that sustains that crucial phenomena of physiological ageing (e.g. inflammaging, cell senescence) propagate and transmit from cell to cell either locally or systemically.

The main aim of PROPAG-AGEING is to identify the combination of specific cellular and molecular alterations capable of shifting the phenotype of elderly subjects from a physiological decline to clinically overt PD. This will eventually allow us to identify markers of early PD diagnosis (before motor symptoms occur) using blood and other body fluids.

To this aim the project will exploit large, very informative cohorts that were previously recruited by PROPAG-AGEING partners: i) a cohort of PD patients, recruited in Italy, Germany, Spain and UK; ii) a cohort of centenarians and their offspring, who never showed clinical signs of motor disability; iii) a cohort of old twins of the Swedish Twin Registry (STR), followed longitudinally for >45 years and assessed for lifestyle and exposure to toxicants, for which incident and prevalent cases of PD discordant twins have been collected. A subset of subjects from these cohorts will be studied by an integrated set of -omic analysis to identify molecular signatures of PD. Emerging biomarkers will be validated in available cohorts and in a newly recruited cohort of siblings of PD patients. In addition, functional in vitro studies will be performed by reprogramming fibroblasts from PD patients and centenarians to dopaminergic neurons via the iPSC protocol.

This approach will allow us to identify new molecular profiles for early diagnosis and therapy (identification of drugable targets) of PD and signatures of healthy ageing.