Low-load blood flow-restricted resistance exercise (BFRRE) constitute an effective means to produce skeletal muscle hypertrophy. Nonetheless, its applicability to counteract the age-related skeletal muscle decay at a cellular level, is not clear. Therefore, we investigated the effect of BFRRE on muscle fiber morphology, integrated muscle protein synthesis, muscle stem cells (MuSCs), myonuclear content and muscle functional capacity in healthy older individuals. Twenty-three participants with a mean age of 66 years (56 to 75 years) were randomized to six weeks of supervised BFRRE (3 sessions x week) or non-intervention control (CON). Biopsies were collected from vastus lateralis before and after the intervention. Immunofluorescent microscopy was utilized to assess muscle fiber type-specific cross-sectional area (CSA) as well as MuSC and myonuclear content. Deuterium oxide was orally administered throughout the intervention period, enabling assessment of integrated myofibrillar and connective tissue protein fractional synthesis rate (FSR). BFRRE produced uniform approximately 20% increases in the fiber CSA of both type I and type II fibers (p < 0.05). This occurred concomitantly with improvements in both maximal strength and muscle strength-endurance, but in the absence of increased MuSC content and myonuclear addition. The observed muscle fiber hypertrophy was not mirrored by increases in either myofibrillar or connective tissue FSR. In conclusion, BFRRE proved effective in stimulating skeletal muscle growth and increased muscle function in older individuals, which advocates for the use of BFRRE as a countermeasure of age-related deterioration of skeletal muscle mass and function.

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