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L’Unité de Nutrition Humaine (UNH - Clermont-Ferrand) organise cette année avec l’aide du laboratoire CarMeN (Lyon) la 18ème éditionL’Unité de Nutrition Humaine (UNH - Clermont-Ferrand) organise cette année avec l’aide du laboratoire CarMeN (Lyon) la 18ème édition; Characterizations of the multiple mechanisms determining biological aging are required tobetter understand the etiology and identify early biomarkers of sarcopenia. Oxylipins are a largefamily of signaling lipids involved in the regulation of various biological processes that becomedysregulated during aging.To investigate whether comprehensive oxylipin profiling could provide an integrated and finecharacterisation of the early phases of sarcopenia, we performed a quantitative targetedmetabolomics of oxylipins in plasma of 81-year old subjects from the PROOF cohort withdecreased (n=12), stable (n=16) or increased appendicular muscle mass (n=14).Multivariate and univariate analyses identified significant and concordant changes of oxylipinprofiles according to the muscle status. Of note, 90% of the most discriminant oxylipins werederived from EPA and DHA and were increased in the sarcopenic subjects. The oxylipinssignatures of sarcopenic subjects revealed subtle activation of inflammatory resolutionpathways, coagulation processes and oxidative stress and the inhibition of angiogenesis. Heatmaps highlighted relationships between oxylipins and the cardiometabolic health parameterswhich were mainly lost in sarcopenic subjects.This exploratory study supports that targeted metabolomics of oxylipins could provide relevantand subtle characterization of early disturbances associated with muscle-loss during aging.

Dietary proteins/essential amino acids (EAAs) are nutrients with anabolic properties that may increase muscle mass or attenuate muscle loss during immobilization and aging via the stimulation of muscle protein synthesis (MPS). An EAA's anabolic threshold, capable to maximize the stimulation of MPS has been hypothesized, but during certain conditions associated with muscle loss, this anabolic threshold seems to increase which reduces the efficacy of dietary EAAs to stimulate MPS. Preliminary studies have demonstrated that acute ingestion of dietary proteins/EAA (with a sufficient amount of leucine) was capable to restore the postprandial MPS during bed rest, immobilization or aging; however, whether these improvements translate into chronic increases (or attenuates loss) of muscle mass is equivocal. For example, although free leucine supplementation acutely increases MPS and muscle mass in some chronic studies, other studies have reported no increases in muscle mass following chronic leucine supplementation. In contrast, chronically increasing leucine intake via the consumption of an overall increase in dietary protein appears to be the most effective dietary intervention toward increasing or attenuating lean mass during aging; however, more research investigating the optimal dose and timing of protein ingestion is necessary. Several studies have demonstrated that decreases in postprandial MPS as a result of increased circulating oxidative and inflammatory are more responsible than muscle protein breakdown for the decreases in muscle mass during disuse and health aging. Therefore, nutritional interventions that reduce oxidation or inflammation in conjunction with higher protein intakes that overcome the anabolic resistance may enhance the MPS response to feeding and either increase muscle mass or attenuate loss. In preliminary studies, antioxidant vitamins and amino acids with antioxidant or anti-inflammatory properties show potential to restore the anabolic response associated with protein ingestion. More research, however, is required to investigate if these nutrients translate to increases in MPS and, ultimately, increased lean mass in aging humans. The purpose of the present review is to discuss the role of protein/EAA intake to enhance postprandial MPS during conditions associated with muscle loss, and bring new perspectives and challenges associated nutritional interventions aimed to optimize the anabolic effects of dietary protein/EAAs ingestion.

We thank Christophe Del'homme, Philippe Denis, Philippe Lhoste and Arlette Cissoire for animal management. We also thank Marion Jourdan, Claire Sornet and Michèle Balage for their precious help. Conceived and designed the experiments: LM ER DD. Performed the experiments: LM EG PG CM DR ISA DD. Analyzed the data: LM DD. Contributed reagents/materials/analysis tools: LM CM DD. Wrote the paper: LM EG.; International audience; Our aim was to compare and combine 3 nutritional strategies to slow down the age-related loss of muscle mass in healthy old rats: 1) increase protein intake, which is likely to stimulate muscle protein anabolism; 2) use leucine rich, rapidly digested whey proteins as protein source (whey proteins are recognized as the most effective proteins to stimulate muscle protein anabolism). 3) Supplement animals with a mixture of chamomile extract, vitamin E, vitamin D (reducing inflammation and oxidative stress is also effective to improve muscle anabolism). Such comparisons and combinations were never tested before. Nutritional groups were: casein 12% protein, whey 12% protein, whey 18% protein and each of these groups were supplemented or not with polyphenols/antioxidants. During 6 months, we followed changes of weight, food intake, inflammation (plasma fibrinogen and alpha-2-macroglobulin) and body composition (DXA). After 6 months, we measured muscle mass, in vivo and ex-vivo fed and post-absorptive muscle protein synthesis, ex-vivo muscle proteolysis, and oxidative stress parameters (liver and muscle glutathione, SOD and total antioxidant activities, muscle carbonyls and TBARS). We showed that although micronutrient supplementation reduced inflammation and oxidative stress, the only factor that significantly reduced the loss of lean body mass was the increase in whey protein intake, with no detectable effect on muscle protein synthesis, and a tendency to reduce muscle proteolysis. We conclude that in healthy rats, increasing protein intake is an effective way to delay sarcopenia.

Communiction orale invitée: Dardevet; International audience

Présentation poster Isabelle Savary-Auzeloux; International audience

Prolonged inactivity induces muscle loss due to an activation of proteolysis and decreased protein synthesis; the latter is also involved in the recovery of muscle mass. The aim of the present work was to explore the evolution of muscle mass and protein metabolism during immobilization and recovery and assess the effect of a nutritional strategy for counteracting muscle loss and facilitating recovery. Adult rats (6–8 months) were subjected to unilateral hindlimb casting for 8 days (I0–I8) and then permitted to recover for 10 to 40 days (R10–R40). They were fed a Control or Experimental diet supplemented with antioxidants/polyphenols (AOX) (I0 to I8), AOX and leucine (AOX + LEU) (I8 to R15) and LEU alone (R15 to R40). Muscle mass, absolute protein synthesis rate and proteasome activities were measured in gastrocnemius muscle in casted and non-casted legs in post prandial (PP) and post absorptive (PA) states at each time point. Immobilized gastrocnemius protein content was similarly reduced (-37%) in both diets compared to the non-casted leg. Muscle mass recovery was accelerated by the AOX and LEU supplementation (+6% AOX+LEU vs. Control, P