Intermediates of phenylpropanoid pathway as substances to prolong lifespan and healthspan

Registration No: 0120U104755

Duration: 21 October 2018 – 31 December 2022
Grant holder: Vasyl Stefanyk Precarpathian National University (Project of the Ministry of Education and Science of Ukraine)

Funding source: National Research Foundation of Ukraine; NRFU Competition “Leading and Young Scientists Research Support”

Application ID: 2020.02/0118

Project abstract
Aging is associated with activation of inflammatory and oxidative processes, mitochondrial dysfunction, formation of specific metabolites, which disturb energy and nutrient metabolism. A range of studies has shown possibility to slowdown aging by anti-aging compounds, or
geroprotectors. We suppose that plant substances, in particular, derivatives of phenylpropanoid (PP) pathway, are capable to slowdown aging, affecting mitochondria. A known example of such geroprotectors is resveratrol. The aim of the current project is to find common and specific mechanisms of anti-aging effects for compounds which affect mitochondria (2,4-dinitrophenol and alpha-ketoglutarate) as well as for derivatives of PP pathway (ferulic acid) and extracts from plants which contain structurally related PPs, namely Rhodiola rosea, chili pepper and anise hyssop. It is also planned to study combined effects of substances with confirmed anti-aging properties, using fruit flies and mice as model organisms.

The goal of the project
To establish common and specific mechanisms underlying anti-aging effects of mitochondrial effectors (2,4-dinitrophenol and alpha-ketoglutarate), individual phenylpropanoids (ferulic acid) and plant preparations with high phenylpropanoid content (anise hyssop, chili pepper and Rhodiola rosea) in model animals, the fruit fly Drosophila melanogaster and mice.

Main tasks of the project
1) To study dose-dependent effects of mitochondrial effectors (alpha-ketoglutarate and 2,4-dinitrophenol), individual phenolic compounds (ferulic acid) and complex plant preparations (of anise hyssop, chili pepper and Rhodiola rosea) on functional state and health indicators of model animals on balanced diet.

2) To explore the effects of the above-mentioned supplements on the intensity of metabolic processes, in particular the parameters of energy metabolism and intensity of free radical processes, in model animals on balanced and high caloric diets.

3) To explore the molecular mechanisms of protective action of the studied supplements by determining the levels of inflammation markers and levels of transcripts and protein products of genes whose expression is regulated by well-known signaling systems related to aging.

4) To study the effects of different combinations of the supplements on lifespan and functional aging of fruit flies.

Project leader: Prof. Maria Bayliak; е-mail: maria.bayliak@pnu.edu.ua