The Influence of Daily Grapes Intake on Sarcopenia in Postmenopausal Women

Sarcopenia, characterized by loss of muscle mass and function, is a prevalent disorder in elderly individuals or individuals with chronic diseases. Given the above, there is an ongoing intensive search for novel therapies, including dietary ones, that can attenuate the loss of muscle mass and strength in the elderly. A proposed mechanism by which skeletal muscles might mediate their protective effect against sarcopenia is by secreting myokines as irisin. Phenolic compounds presents in grape have shown to be able to induce irisin secretion in muscle from rats supplemented with a grape pomace extract. The Ian of this study is to evaluate this mechanism in humans.

Scientific rationale Sarcopenia, characterized by loss of muscle mass and function, is a prevalent disorder in elderly individuals or individuals with chronic diseases. It leads to fragility and disability, worsens the prognosis of many diseases, and significantly enhances morbidity and mortality. With the increasing life expectancy and rapid growth of the aged population, sarcopenia is becoming an emerging public health issue with huge socioeconomic burden.

Given the above, there is an ongoing intensive search for novel therapies, including dietary ones, that can attenuate the loss of muscle mass and strength in the elderly. Interestingly, a growing body of research indicate that nutritional factors can preserve muscle function from age- related decline. In particular, phenolic compounds, widely distributed in fruits including grapes, have shown beneficial effects in muscle health. However, the exact influence of grapes and grapes phenolic compounds mitigating sarcopenia in humans remains unexplored.

A proposed mechanism by which skeletal muscles might mediate their protective effect against sarcopenia is by secreting myokines. Irisin is a myokine regulated by peroxisome proliferator- activated receptor gamma co-activator-1α (PGC-1α) and released into the bloodstream after cleavage of the Fibronectin type III domain-containing protein 5 (FNDC5). Recent studies have indicated that circulating irisin can promote skeletal muscle growth. Lower irisin concentrations have been observed in sarcopenia patients and dialyzed patients with cardiovascular disease. Furthermore, lower irisin plasma levels are associated with sarcopenia in postmenopausal women.

In a recent study, it have been shown that phenolic compounds present in a grape pomace extract (GPE), rich in phenolic compounds, prevent irisin downregulation in rats fed a high-fat diet and in L6 myotube cells. In particular, we documented that consumption of the GPE activates the FNDC5/irisin pathway, increased AMPK phosphorylation in skeletal muscle and increased irisin plasma levels. These data strongly indicate that phenolic compounds enhance irisin levels in vitro and in vivo. These intriguing data allow us to hypothesize that phenolic compounds present in grapes might prevent sarcopenia in elderly humans, in part, by increasing irisin levels.

Specific objectives

The objective of this proposal is to evaluate whether the daily consumption of a freeze-dried table grape powder, rich in phenolic compounds, mitigates sarcopenia in postmenopausal women. The hypothesis is that daily dietary supplementation with a grape powder improves health span, mitigates sarcopenia parameters and increases irisin plasma levels in postmenopausal women. To test this hypothesis, the following aims will be pursued:

• To determine the efficacy of a freeze-dried table grape powder, rich in phenolic compounds, to mitigate sarcopenia parameters in postmenopausal women.
• To evaluate the effect of a freeze-dried table grape powder on key metabolic regulators of sarcopenia in postmenopausal women.