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other·preclinical research, nutrition, geriatrics, biomedical research·PMC10067497

Dietary phosphate restriction prevents the appearance of sarcopenia signs in old mice

Journal of Cachexia, Sarcopenia and Muscle · 9 authors, 8 centres

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TL;DR

This preclinical study in old mice found that restricting dietary phosphate improved muscle mass, strength, and physical performance compared to a standard diet, suggesting phosphate reduction as a potential strategy against age-related muscle decline.

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The study investigated whether dietary phosphate restriction could prevent sarcopenia signs in an aging mouse model. Old and geriatric male C57BL6 mice were fed either a standard diet (0.6% phosphate) or a low-phosphate diet (0.2%) for 3 or 7 months, respectively. Some old mice also received a phosphate binder, Velphoro®, with their diet. Similar benefits were observed with Velphoro® supplementation. The study demonstrates in this animal model that reducing phosphate intake mitigates age-related muscle decline.

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other

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preclinical research

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ORIGINAL PAPER

PMC10067497

Dietary phosphate restriction prevents the appearance of sarcopenia signs in old mice

Journal of Cachexia, Sarcopenia and Muscle

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ABSTRACT

Abstract Background Sarcopenia is defined by the progressive and generalized loss of muscle mass and function associated with aging. We have previously proposed that aging‐related hyperphosphataemia is linked with the appearance of sarcopenia signs. Because there are not effective treatments to prevent sarcopenia, except for resistance exercise, we propose here to analyse whether the dietary restriction of phosphate could be a useful strategy to improve muscle function and structure in an animal model of aging. Methods Five‐month‐old (young), 24‐month‐old (old) and 28‐month‐old (geriatric) male C57BL6 mice were used. Old and geriatric mice were divided into two groups, one fed with a standard diet (0.6% phosphate) and the other fed with a low‐phosphate (low‐P) diet (0.2% phosphate) for 3 or 7 months, respectively. A phosphate binder, Velphoro®, was also supplemented in a group of old mice, mixed with a standard milled diet for 3 months. Muscle mass was measured by the weight of gastrocnemius and tibial muscles, and quality by nuclear magnetic resonance imaging (NMRI) and histological staining assays. Muscle strength was measured by grip test and contractile properties of the tibialis muscle by electrical stimulation of the common peroneal nerve. Gait parameters were analysed during the spontaneous locomotion of the mice with footprinting. Orientation and motor coordination were evaluated using a static rod test. Results Old mice fed with low‐P diet showed reduced serum phosphate concentration (16.46 ± 0.77 mg/dL young; 21.24 ± 0.95 mg/dL old; 17.46 ± 0.82 mg/dL low‐P diet). Old mice fed with low‐P diet displayed 44% more mass in gastrocnemius muscles with respect to old mice ( P = 0.004). NMRI revealed a significant reduction in T2 relaxation time ( P = 0.014) and increased magnetization transfer ( P = 0.045) and mean diffusivity ( P = 0.045) in low‐P diet‐treated mice compared with their coetaneous. The hypophosphataemic diet increased the fibre size and reduced the fibrotic area by 52% in gastrocnemius muscle with respect to old mice ( P = 0.002). Twitch force and tetanic force were significantly increased in old mice fed with the hypophosphataemic diet ( P = 0.004 and P = 0.014, respectively). Physical performance was also improved, increasing gait speed by 30% ( P = 0.032) and reducing transition time in the static rod by 55% ( P = 0.012). Similar results were found when diet was supplemented with Velphoro®. Conclusions The dietary restriction of phosphate in old mice improves muscle quantity and quality, muscle strength and physical performance. Similar results were found using the phosphate binder Velphoro®, supporting the role of phosphate in the impairment of muscle structure and function that occurs during aging.

CITATION EXPORT

Elena Alcalde‐Estévez, Patricia Sosa, Ana Asenjo‐Bueno et al.. Dietary phosphate restriction prevents the appearance of sarcopenia signs in old mice. Journal of Cachexia, Sarcopenia and Muscle. (2023). https://doi.org/10.1002/jcsm.13194

AUTHORS

9 · 8 CENTRES

Elena Alcalde‐Estévez, Patricia Sosa, Ana Asenjo‐Bueno, Patricia Plaza, Pedro L. Valenzuela, Manuel Naves‐Díaz, Gemma Olmos, Susana López‐Ongil, María P. Ruiz‐Torres

1 Universidad de Alcalá, Facultad de Medicina y Ciencias de la Salud, Departamento de Biología de Sistemas Universidad de Alcalá 28871 Madrid Alcalá de Henares Spain
2 Unidad de Investigación de la Fundación para la Investigación Biomédica del Hospital Universitario Príncipe de Asturias Alcalá de Henares, Madrid Spain
3 Fundación para la investigación Biomédica del Hospital Universitario de Getafe Getafe Spain
4 Unidad de Investigación Clínica de Cáncer de Pulmón H120‐CNIO Madrid Spain
5 Physical Activity and Health Research Group (PaHerg) Instituto de Investigación Sanitaria Hospital ‘12 de Octubre’ (‘imas12’) Madrid Spain
6 Unidad de Gestión Clínica de Metabolismo Óseo, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) Oviedo Spain
7 Instituto Reina Sofía de Investigación Nefrológica (IRSIN) de la Fundación Renal Iñigo Álvarez de Toledo (FRIAT) Madrid Spain
8 Área 3‐Fisiología y Fisiopatología Renal y Vascular del IRYCIS Madrid Spain