New ways of measuring health improvement

5 June 2017 –

Prolonged, resistance-type exercise training can shift skeletal muscle tissue towards a ‘younger’ phenotype. This is one of the key findings from research by Parastoo Fazelzadeh, who successfully defended her thesis on May 11th 2017 at Wageningen University. Her work has provided industry and academia with new ways to measure health improvement.

Health is affected by a complex network of interactions between biological pathways, mechanisms, processes and organs, all continuously adapting to a dynamically-changing environment. This adaptability is called phenotypic flexibility. “According to systems biologists health is compromised, and diseases develop, when these adaptive processes fail”, explains Fazelzadeh. “An individual’s metabolic phenotype, the product of interactions between several factors such as genetic makeup, diet, lifestyle, environment and the gut microbiome, can provide a reliable record of that person’s health status. But only if the interactions between all these factors are well understood”, she stresses.

Studying phenotype shifts
The aim of Fazelzadeh’s research, which was part of TiFN’s Muscle and Cardiovascular Health projects, was to provide new insight into these interactions. The PhD fellow investigated phenotype shifts by looking at the effect of prolonged, resistance-type exercise training on skeletal muscle tissue in older subjects, and the possible shift towards the characteristics of younger subjects as a reference for a healthier phenotype. With the same idea in mind, she looked at the response of obese subjects to a mixed-meal challenge (a meal containing two muffins and 300 ml milk, which accounted for 1,100 kilocalories), identifying phenotypic shifts towards the metabolism of non-obese subjects.

The PhD fellow found that healthy, but frail, older people have two distinct phenotypes according to their skeletal muscle-tissue-metabolite profiles. “Moreover, exercise training shifts older muscle towards a younger phenotype”, she says. Exercise substantially increased levels of amino-acid-derived acylcarnitines in muscle tissue, pointing towards a decrease in branched-chain amino-acid catabolism. The trial with obese people appeared to show that weight loss moderately affects the response to a mixed meal of the plasma metabolome and the transcriptome of peripheral blood mononuclear cells.

Innovative approach
For the measurements, Fazelzadeh and her colleagues used an innovative approach, combining a comprehensive metabolics platform with extended statistics. “We are one of the first projects to apply such a comprehensive approach”, she says. “We have optimized these approaches to facilitate food-industry use in, for example, the substantiation of mechanisms underlying potential health benefits.” Wageningen University scientists are already using these approaches in a follow-up project.