AUTHOR=Conte Elena , Mantuano Paola , Boccanegra Brigida , Imbrici Paola , Dinoi Giorgia , Lenti Roberta , Cappellari Ornella , Cappetta Donato , De Angelis Antonella , Berrino Liberato , Gordish-Dressman Heather , Bianchini Gianluca , Aramini Andrea , Allegretti Marcello , Liantonio Antonella , De Luca Annamaria 

TITLE=Branched-chain amino acids and L-alanine supplementation ameliorate calcium dyshomeostasis in sarcopenia: New insights for nutritional interventions

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1393746

DOI=10.3389/fphar.2024.1393746

ISSN=1663-9812

ABSTRACT=During aging, sarcopenia and decline in physiological processes lead to partial loss of muscle strength, atrophy, and increased fatigability. Muscle changes may be related to a reduced intake of essential amino acids playing a role in proteostasis. We have recently shown that branched-chain amino acid (BCAA) supplements, improve atrophy and weakness in models of muscle disuse and aging. Considering the key role that the alteration of Ca 2+ -related homeostasis and store-operatedcalcium-entry (SOCE), plays in several muscle dysfunctions, this study has been aimed at gaining insight into the potential ability of BCAA-base dietary formulations in aged mice on various players of Ca 2+ dyshomeostasis. Methods. 17-months-old male C57BL/6J mice received a 12-weekssupplementation with BCAAs alone or boosted with two equivalents of L-Alanine (2-Ala) or with dipeptide L-Alanyl-L-Alanine (Di-Ala), in drinking water. Outcomes were evaluated on ex vivo skeletal muscles indices vs adult 3-months-old male C57BL/6J mice. Results. Ca 2+ imaging confirmed a decrease in SOCE and an increase of resting Ca 2+ concentration in aged vs adult mice without alteration in the canonical components of SOCE. Aged muscles vs adult ones were characterized by a decrease in the expression of the Ryanodine Receptor 1 (RyR1), Sarco-Endoplasmic Reticulum Calcium ATPase (SERCA) pump and sarcalumenin together with an alteration of the expression of Mitsugumin29 and Mitsugumin53, two recently recognized players in SOCE mechanism. BCAAs, particularly the formulation BCAAs+2-Ala, were able to ameliorate all these alterations. Discussion. These results provide evidence that Ca 2+ homeostasis dysfunction plays a role in the functional deficit observed in aged muscle and support the interest of dietary BCAA supplementation in counteracting sarcopenia related SOCE dysregulation.