Grant: Discovery Grants Program - Individual

Aging is a natural physiological process concomitant with fat mass accumulation. This age-associated fat accumulation acts synergistically with muscle mass loss, potentially leading to metabolic dysregulation (e.g. insulin resistance), indicating fat-muscle communication in regulating metabolic functions. Furthermore, the synthesis of fat molecules that reduce inflammation is also reduced  in aging, possibly due to an excess of omega-6 fatty acids metabolites and decreased biosynthesis of fat mediators from omega-3 fatty acids. Higher consumption of omega-6 fatty acids, typically 15 times more than omega-3 fatty acids in western diet, results in higher synthesis of omega-6 and their metabolites at the expense of omega-3 fatty acids. Omega-6 are linked to inflammation while omega-3 have anti-inflammatory properties. The derivatives of omega-3 are collectively named 'specialized pro-resolving lipid mediators, which actively limit inflammation and promote its resolution. Recent evidence indicates a promising role for lipid derived from omega-3, as pro-resolving lipid mediators to enhance muscle regeneration. It seems that generation of a less pro-inflammatory environment results in reduced muscle mass loss. Mechanistically, the effects of omega-3 and its derived metabolites could be partly mediated by activation of the pathway involved in the muscle protein synthesis as well as the inhibition of inflammation. However, research regarding the mechanisms underlying omega-3 effects on muscle lipid mediator content and the modulation of fat-muscle crosstalk during natural aging, is lacking. This research program aims to understand mechanisms of fat-muscle-bone crosstalk and its impacts on tissue homeostasis and to determine if tissue crosstalk may be modulated using stimuli (nutrition, exercise) to promote healthy aging. More specifically, we will determine the effects of omega-3 on muscle mass and muscle lipid mediator content in aging. We will use specialized imaging techniques and chemical analysis to measure the impact of omega-3 fatty acid supplementation in a longitudinal study using a rodent model. Moreover, we will evaluate the impacts of omega-6 on adipogenesis and muscle degeneration. We will examine the effects of high omega-6 on adipogenesis and fat-muscle crosstalk in fat cells and muscle cells using cell and co-culture methods. This research will: 1) provide a mechanistic understanding of muscle mass loss during the natural aging process; 2) uncover mechanisms by which omega-3 modulate muscle mass loss in aging; 3) provide evidence to support strategies for healthy aging; and 4) train the next generation of scientists with necessary research skills and prepare them to significantly contribute to the Canadian scientific community.