Caloric Restriction Rejuvenates Skeletal Muscle Growth in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a major clinical problem, with limited treatments. HFpEF is characterized by a distinct, but poorly understood, skeletal muscle pathology, which could offer an alternative therapeutic target. In a rat model, we identified impaired myonuclear accretion as a mechanism for low myofiber growth in HFpEF following resistance exercise. Acute caloric restriction rescued skeletal muscle pathology in HFpEF, whereas cardiac therapies had no effect. Mechanisms regulating myonuclear accretion were dysregulated in patients with HFpEF. Overall, these findings may have widespread implications in HFpEF, indicating combined dietary with exercise interventions as a beneficial approach to overcome skeletal muscle pathology.

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© 2024 The Authors.

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Dr Espino-Gonzalez is a recipient of a doctoral fellowship from the Mexican National Council of Science and Technology (CONACYT). Dr Altara’s work was supported by a grant from the K.G. Jebsen Center for Heart Failure Research. Dr Cheng is supported by BHF Mautner Career Development Fellowship. Dr Justo da Silva was supported by the South-Eastern Norway Regional Health Authority (HSØ-RHF, Project No. 25674). Dr Booz has received support from the Pharmacology Clinical Research Core of the University of Mississippi Medical Center School of Medicine. Dr Bowen has received funding from the Medical Research Council (UK) (MR/S025472/1) and Heart Research UK (TRP16/19). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.