Project: Targeting the mitochondria-tyr-kinase axis to prevent age-associated neuronal decline

Acronym	MiTyrAge
Duration	01/05/2016 - 31/12/2019
Project Topic	Mitochondria represent central regulators of nutritional homeostasis and of the aging process. Epidemiological studies, including data from our cohort, indicate nutritional risk and preventive factors associated with dietary intake for the development of age-related parameters. Notably, recent studies from this network revealed the importance of a finely tuned mitochondria-autophagy axis as a preventive mechanism against aging. However, whether and how specific dietary interventions can modulate mitochondrial function in turn impacting on age-associated neuronal and cognitive decline is largely unknown. Tyr-kinases are lately emerging as important regulators of mitochondrial function and have been also implicated in the development of age-associated disorders. Here we want to specifically address whether selected nutrients, mainly polyphenols founds in fruits and vegetables, regulate a mitochondria-tyr kinase crosstalk, to delay/prevent the neuronal and cognitive decline observed during physiological and accelerated aging. Through four distinct but complementary working packages our specific aims are: (i) to assess whether selected nutritional factors are associated with and can delay age-related neuronal changes (WP1-2); (ii) to unravel underlying molecular mechanisms of selected nutritional factors through targeted (i.e. the mitochondrial-tyr kinases axis), and unbiased approaches (i.e. GWAS and –omics studies (WP1-3); (iii) to assess the implications of relevant pathways and interventions to alleviate cognitive disorders in mice (WP1&4). This proposal brings together an original combination of complementary model systems and expertise to untangle novel molecular mechanisms for selected nutritional factors in protecting against age-associated cognitive disorders. A key asset of our network is the coupling of basic experimental research using different model systems (i.e. in vitro mechanistic studies on mammalian cells; in vivo lifespan and neuronal behavioural assays in C. elegans and mice) and epidemiological research (association studies on the SALIA longitudinal cohort for pre-dementia disorders). Through this interdisciplinary, transnational work, the present consortium will therefore ultimately deliver biological outputs that may suggest novel molecular mechanisms and preventive strategies for future clinical studies.
Project Results (after finalisation)	The results of the consortium indicated that flavonoids (like quercetin, abundant in the Mediterranean diet) mainly found in fruits and vegetables can help to delay age-associated neuronal decline and associated neuronal pathologies like Alzheimer’s disease.
Network	JPI HDHL
Call	NUTRICOG

Project partner

Number	Name	Role	Country
1	Centro de Biologia Molecular Severo Ochoa	Coordinator	Spain
2	Medical Faculty of the Heinrich Heine University	Partner	Germany
3	IUF – Leibniz Research Institute for Environmental Medicine	Partner	Germany
4	University of Rome “Tor Vergata”	Partner	Italy