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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1393746
Branched-Chain Amino Acids and L-Alanine supplementation ameliorates calcium dyshomeostasis in sarcopenia: new insights for nutritional interventions
Provisionally accepted
Elena Conte
1
Paola Mantuano
1
Brigida Boccanegra
1
Paola Imbrici
1
Giorgia Dinoi
1
Roberta Lenti
1
Ornella Cappellari
1
Donato Cappetta
2
Antonella De Angelis
3
Liberato Berrino
3
Gianluca Bianchini
4
Andrea Aramini
4
Marcello Allegretti
4
Antonella Liantonio
1
Annamaria De Luca
1*- 1 University of Bari Aldo Moro, Bari, Italy
- 2 University of Salento, Lecce, Apulia, Italy
- 3 University of Campania Luigi Vanvitelli, Caserta, Campania, Italy
- 4 Dompé farmaceutici S.p.A., Milano, Italy
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.
Keywords: Branched-chain amino acids, Sarcopenia, calcium homeostasis, skeletal muscle, L-alanine
Received: 29 Feb 2024; Accepted: 24 May 2024.
Copyright: © 2024 Conte, Mantuano, Boccanegra, Imbrici, Dinoi, Lenti, Cappellari, Cappetta, De Angelis, Berrino, Bianchini, Aramini, Allegretti, Liantonio and De Luca. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Annamaria De Luca, University of Bari Aldo Moro, Bari, Italy
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