ESR15: “Evaluation of nutraceuticals against age-related diseases”

Nagi Bioscience: Evaluation of nutraceuticals against age-related diseases

i. Objective of research: To test natural compounds on ageing and age-related disease models available amongst the HealthAge network.

ii. Current state of the art: Mitochondrion is a central organelle that can drive both cellular life, i.e. by producing energy in the respiratory chain, and death, i.e. by initiating apoptosis. Dysfunctional mitochondria can be specifically targeted for elimination by autophagy, a process that has been termed mitophagy. During ageing, there is a progressive decline in the cell capacity to eliminate its dysfunctional elements by autophagy. Therefore, restoring levels of autophagy and mitophagy and boosting mitochondrial function in the elderly represents a promising approach to halt the development of age related disorders. In this respect, Nagi Bioscience’s scientists contributed, for instance, to the identification of Urolithin A (UA) as the first inducer of mitophagy, which makes it today a strong candidate for age-associated conditions. To serve this research field, moreover, the company developed an innovative microfluidic-based platform for high-content screening on the worm C. elegans. This technology allows testing potential drugs and nutraceuticals against age-related diseases at unprecedented levels of automation and multi-parametric data collection capacity.

iii. Research methodology and approach: In the current project, Nagi Bioscience will first characterize the anti-ageing effects of relevant compounds (e.g. UA) by using its innovative technology in combination with other pre-clinical models available amongst the HealthAge network. The aims of this part of the project will be to (1) investigate the relationship between mitophagy and other mechanisms of ageing, (2) optimize the use of the microfluidic platform for the creation of novel pre-clinical bioassays specifically tailored for ageing research. In a second project phase, then, Nagi Bioscience will carry out a detailed characterization of a series of naturally derived ingredients using the previously optimized set of bioassays and models, in order to select the best ones for potential further development toward the clinic. The primary model of choice will be C. elegans strains, a particularly useful tool to measure the impact of the compounds on lifespan extension and age-related phenotypes. In addition, mutant strains that are model for age-related disorders (e.g. neurodegenerative disorders) or worms that carry mutations in genes of the Nucleotide Excision Repair pathway will be tested. The best compounds and conditions identified in worms will be tested in vitro and in rodent models through further collaborations.

iv. Originality and innovative aspects of the ESR project: We propose to (1) use mitophagy inducers in combination with an innovative C. elegans-based screening technology to understand the relationship between mitochondrion and other mechanisms of ageing and (2) identify other natural compounds with potent anti-ageing effects.

v. Integration of the ESR project to the overall research programme: Our ESR will test the impact of specialized nutraceuticals on mitophagy (with the Auwerx group), on DNA damage responses (with the Schumacher group) and on NER progeria (with the Garinis group).